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Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT31-1 for Treating ARDS
Lacey Harris, MPH, BSN - Lacey.Harris@vcuhealth.org
NCT07449572
Inclusion Criteria:
Participants must meet all of the following criteria:
• Age 18 to 65 years old, inclusive, at the time of consent.
• Able and willing to provide written informed consent and to comply with all study procedures and requirements.
• Healthy as determined by medical history, physical examination, and baseline investigations. No clinically significant abnormalities on physical exam.
• Body Mass Index (BMI) between 18.0 and 32.0 kg/m², inclusive.
• Vital signs and 12-lead ECG without clinically significant abnormalities, in the investigator's judgment, at screening (e.g., resting blood pressure and heart rate within normal limits).
• Screening clinical laboratory tests (hematology, chemistry, liver and kidney function, etc.) within normal ranges or not clinically significant as judged by the investigator.
• Female volunteers must be of non-childbearing potential (either surgically sterile by tubal ligation, bilateral oophorectomy or hysterectomy at least 6 months prior, or postmenopausal for ≥1 year) OR if of childbearing potential must agree to use 2 approved effective contraceptions from screening through at least 90 days after the last dose. Acceptable methods include hormonal contraception, intrauterine device, or barrier methods with spermicide.
• Male volunteers with partners of childbearing potential must agree to use 2 approved effective contraception (e.g., condom plus spermicide) from screening through 90 days after their dose of study drug.
• Able to communicate well with the investigator and comply with study requirements (e.g., availability for all follow-up visits).
Exclusion Criteria:
Participants will be excluded if they meet any of the following criteria:
• History of any severe allergy or hypersensitivity to drugs, or known hypersensitivity to any monoclonal antibody (including prior biologic therapy reactions).
• Known autoimmune disease or immunodeficiency condition, including a positive test for HIV at screening.
• Active or chronic viral hepatitis infection: positive screening test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody.
• History of tetanus infection, or receipt of tetanus toxoid vaccine within 6 months prior to first dose of study drug. (Rationale: CitH3 is associated with NETs, and recent tetanus immunization may confound immune status or antibody responses).
• Receipt of any live attenuated vaccine within 4 weeks prior to first dose, or any inactivated vaccine within 2 weeks prior to first dose. (This is to avoid confounding immune activation or risk to the volunteer's health).
• History of any significant acute or chronic illness that, in the investigator's opinion, could interfere with the trial or pose additional risk in administering the investigational drug. Examples include significant cardiovascular, hepatic, renal, gastrointestinal, hematologic, neurologic, psychiatric, or respiratory conditions that are not well-controlled.
• Recent major surgery (within 3 months prior to screening) or planned elective surgery during the study period. (Minor outpatient procedures are allowed at the investigator's discretion.)
• Difficulty with venous access or an inability to tolerate blood draws, such that required PK sampling would be compromised.
• History of drug or alcohol abuse: positive urine drug screen at screening for illicit substances, or a history of significant drug abuse in the past 5 years. Regular use of cannabis is also exclusionary unless stopped prior to study.
• Positive screening alcohol breath test, or history of excessive alcohol intake (more than \~14 units per week; 1 unit = 360 mL beer, 150 mL wine, or 45 mL of 40% spirit) within 6 months. Any indication of alcoholism or inability to refrain from alcohol during study participation.
• Use of any prescription or over-the-counter medications, herbal remedies, or supplements within 14 days prior to first dose, except hormonal contraceptives or occasional acetaminophen. (Any necessary medications may be reviewed by the investigator for approval if unlikely to interfere with study outcomes).
• Participation in another clinical trial of an investigational drug or device within 4 weeks (or 5 half-lives of that investigational product, whichever is longer) prior to dosing.
• Donation of \>400 mL of blood (or significant blood loss of similar volume) within 3 months prior to screening, or donation of \>200 mL within 1 month prior. (This is to avoid anemia or confounding volume loss).
• Receipt of any blood products or immunoglobulin therapy within 90 days before dosing.
• Chronic use of immunosuppressive medications (systemic corticosteroids, immunomodulators) within 45 days before dosing (inhaled/topical steroids for mild conditions may be permitted).
• Regular use of nicotine products (smoking more than 5 cigarettes per day or equivalent) within 3 months prior to screening, or inability to refrain from tobacco/nicotine during the study.
• Pregnant or breastfeeding women. (Female volunteers must have a negative pregnancy test and not be nursing.)
• Any other condition that, in the opinion of the investigator, makes the volunteer unsuitable for study participation (e.g. inability to comply with protocol, or any factor that would jeopardize the volunteer's safety or the validity of the data).
DRUG: HT31-1, OTHER: Saline (0.9%, sterile, for infusion)
ARDS (Acute Respiratory Distress Syndrome)
Acute Respiratory Distress Syndrome (ARDS), Single Ascending Dose, Monoclonal Antibody
A Study to Compare Elritercept With Epoetin Alfa to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Who Need Regular Blood Transfusions (ELRiSE MDS)
Takeda Contact - medinfoUS@takeda.com
NCT07422480
Inclusion Criteria
• Male or female participants aged ≥ 18 years or older at time of signing the informed consent form (ICF).
• Able to understand the purpose and risks of the trial and voluntarily sign an ICF prior to any trial-related procedures being conducted and authorization to use protected health information and personal data in accordance to national and local privacy regulations.
• Documented diagnosis of myelodysplastic syndrome(s) (MDS) according to WHO 2016 classification that meets International Prognostic Scoring System - Revised (IPSS-R) classification of very low-, low-, or intermediate-risk disease, confirmed by central laboratory independent reviewer prior to randomization. Hemoglobin (Hgb), platelet, and absolute neutrophil count (ANC) values should be collected greater than (\>) 14 days after red blood cell (RBC) transfusion or greater than (\>) 7 days after platelet transfusion, unless otherwise considered to be pretransfusion values.
• Bone marrow less than (\<) 5% blasts in an evaluable bone marrow collected at screening and confirmed by central pathology independent reviewer.
• Endogenous serum erythropoietin s (EPO) level of \<500 U/L. Should be results from blood samples collected \>14 days following an RBC transfusion to evaluate for eligibility unless considered pretransfusion values.
• Participant requires RBC transfusion, as documented by the following criteria. A transfusion requirement of 2 to 6 pRBCs units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization. • Hgb levels at the time of or within 3 days prior to administration of a RBC transfusion must have been less than or equal to (≤) 9.0 grams per deciliter (g/dL) (5.6 millimoles per liter (mmol/L)) with symptoms of anemia (or ≤7 g/dL \[4.3 mmol/L\] in the absence of symptoms) in order for the transfusion to be counted towards meeting eligibility criteria. • RBC transfusions administered when hemoglobin (Hgb) levels were \>9.0 g/dL (or \>7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification.
• Hgb \<11.0 g/dL (6.8 mmol/L) after last RBC transfusion preceding randomization. Local laboratory is acceptable to facilitate randomization.
• Eastern Cooperative Oncology Group score of 0, 1, or 2. Exclusion Criteria
• Prior therapy with any of the following:
• Epoetin alfa • At the investigator's discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of only epoetin alfa ≥8 weeks prior to randomization. No other erythropoiesis-stimulating agent (ESA) agent is allowed.
• Darbepoetin
• Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administered ≤8 weeks (56 days) prior to randomization unless given for treatment of febrile neutropenia.
• Immunomodulatory drug (IMiDs) including lenalidomide • At the investigator's discretion in consultation with the medical monitor may be allowed if received ≤1 week of an IMiD ≥8 weeks prior to randomization.
• Hypomethylating agent • At the investigator's discretion, in consultation with the medical monitor may be allowed if received no more than 2 doses ≥8 weeks prior to randomization.
• Luspatercept, sotatercept, imetelstat, or elritercept
• Immunosuppressive therapy
• Hematopoeitic cell transplant
• Iron chelation if administered ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed Vitamin B12 or folate therapy initiated within 4 weeks prior to randomization. Participants on stable replacement doses for ≥4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed.
• Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed
• High-dose corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone ≤10 mg/day or corticosteroid equivalent for ≥ 4 weeks are allowed. Other disease modifying treatments for autoimmune diseases may be allowed upon medical monitor review.
• Investigational agent or any other agent intended for treatment MDS treatment
• Diagnosed to have MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable according to WHO 2016 classification or secondary MDS.
• Known history of diagnosis of acute myeloid leukemia (AML).
• Anemia due to any other known cause including but not limited to thalassemia; hypothyroidism; due to iron, vitamin B12, vitamin B6, zinc, or folate deficiencies; autoimmune or hereditary hemolytic anemia; any type of known clinically significant bleeding or sequestration or drug induced anemia, hemolytic anemia, or bleeding events.
• Clinically significant cardiovascular disease defined as:
• New York Heart Association heart disease class III or IV
• Fridericia corrected QT (QTcF) interval \>500 milliseconds during screening
• Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening
• Known ejection fraction \<35%, confirmed by a local echocardiogram performed during screening, or a previously performed echocardiogram if collected within 6 months before screening.
• Medical history of thromboembolic events within 6 months before screening, including history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism, arterial thrombosis or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
• Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
• Prior history of malignancies, other than MDS. Participants who are free of other malignant disease for ≥3 years and have completed treatment, including maintenance are allowed. Participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy:
• Basal or squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix;
• Carcinoma in situ of the breast;
• Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis \[TNM\] clinical staging system).
• History of solid organ or bone marrow transplantation.
• Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before randomization.
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
• Body mass index ≥ 40 kilograms per square meter (kg/m\^2).
• Major surgery within 28 days before randomization.
• New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization are excluded from trial participation.
• History of allergy/anaphylaxis to investigational product (including epoetin alfa) excipients (refer to the current elritercept investigator's brochure for a list of excipients) or recombination proteins.
• History of pure red cell aplasia and/or antibody against erythropoietin (EPO).
• Any of the following laboratory abnormalities:
• ANC \<500/microliter (μL) (0.5×109/L).
• Platelet count \<50,000/μL (50×109/L) or ≥450,000/μL (450×109/L).
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3× upper limit of the normal (ULN).
• Total bilirubin ≥2×ULN. Participants with known history of Gilbert syndrome with unconjugated bilirubin \<3×ULN are allowed. Higher levels if attributed to active RBC precursor destruction within the bone marrow (ineffective erythropoiesis) may be allowed upon medical monitor review.
• Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2 as determined by the Chronic Kidney Disease Epidemiology (CKD-EPI) collaboration equation.
• Ferritin ≤50 micrograms per liter (μg/L).
• Folate ≤2.0 nanograms per milliliter (ng/mL).
• Vitamin B12 ≤200 picograms per milliliter (pg/mL).
• Ongoing participation in another interventional clinical trial.
• Participant is unwilling or in the opinion of the investigator the participant is unable to comply with the requirements of the protocol.
• Is a participant of childbearing potential (POCBP) but does not agree to use at least 1 form of highly effective contraception from the time of signing the ICF until at least 60 days after the last dose of trial intervention.
• Participants of male birth who are fertile and who have partners of childbearing potential, who do not agree to use acceptable barrier contraception, that is, a male condom during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
• If applicable, participant with a positive serum pregnancy test during the screening period or known to be pregnant or a lactating participant who does not agree to forego breastfeeding during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
• For Participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults.
• Male or female participants aged ≥ 18 years or older at time of signing the informed consent form (ICF).
• Able to understand the purpose and risks of the trial and voluntarily sign an ICF prior to any trial-related procedures being conducted and authorization to use protected health information and personal data in accordance to national and local privacy regulations.
• Documented diagnosis of myelodysplastic syndrome(s) (MDS) according to WHO 2016 classification that meets International Prognostic Scoring System - Revised (IPSS-R) classification of very low-, low-, or intermediate-risk disease, confirmed by central laboratory independent reviewer prior to randomization. Hemoglobin (Hgb), platelet, and absolute neutrophil count (ANC) values should be collected greater than (\>) 14 days after red blood cell (RBC) transfusion or greater than (\>) 7 days after platelet transfusion, unless otherwise considered to be pretransfusion values.
• Bone marrow less than (\<) 5% blasts in an evaluable bone marrow collected at screening and confirmed by central pathology independent reviewer.
• Endogenous serum erythropoietin s (EPO) level of \<500 U/L. Should be results from blood samples collected \>14 days following an RBC transfusion to evaluate for eligibility unless considered pretransfusion values.
• Participant requires RBC transfusion, as documented by the following criteria. A transfusion requirement of 2 to 6 pRBCs units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization. • Hgb levels at the time of or within 3 days prior to administration of a RBC transfusion must have been less than or equal to (≤) 9.0 grams per deciliter (g/dL) (5.6 millimoles per liter (mmol/L)) with symptoms of anemia (or ≤7 g/dL \[4.3 mmol/L\] in the absence of symptoms) in order for the transfusion to be counted towards meeting eligibility criteria. • RBC transfusions administered when hemoglobin (Hgb) levels were \>9.0 g/dL (or \>7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification.
• Hgb \<11.0 g/dL (6.8 mmol/L) after last RBC transfusion preceding randomization. Local laboratory is acceptable to facilitate randomization.
• Eastern Cooperative Oncology Group score of 0, 1, or 2. Exclusion Criteria
• Prior therapy with any of the following:
• Epoetin alfa • At the investigator's discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of only epoetin alfa ≥8 weeks prior to randomization. No other erythropoiesis-stimulating agent (ESA) agent is allowed.
• Darbepoetin
• Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administered ≤8 weeks (56 days) prior to randomization unless given for treatment of febrile neutropenia.
• Immunomodulatory drug (IMiDs) including lenalidomide • At the investigator's discretion in consultation with the medical monitor may be allowed if received ≤1 week of an IMiD ≥8 weeks prior to randomization.
• Hypomethylating agent • At the investigator's discretion, in consultation with the medical monitor may be allowed if received no more than 2 doses ≥8 weeks prior to randomization.
• Luspatercept, sotatercept, imetelstat, or elritercept
• Immunosuppressive therapy
• Hematopoeitic cell transplant
• Iron chelation if administered ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed Vitamin B12 or folate therapy initiated within 4 weeks prior to randomization. Participants on stable replacement doses for ≥4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed.
• Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed
• High-dose corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone ≤10 mg/day or corticosteroid equivalent for ≥ 4 weeks are allowed. Other disease modifying treatments for autoimmune diseases may be allowed upon medical monitor review.
• Investigational agent or any other agent intended for treatment MDS treatment
• Diagnosed to have MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable according to WHO 2016 classification or secondary MDS.
• Known history of diagnosis of acute myeloid leukemia (AML).
• Anemia due to any other known cause including but not limited to thalassemia; hypothyroidism; due to iron, vitamin B12, vitamin B6, zinc, or folate deficiencies; autoimmune or hereditary hemolytic anemia; any type of known clinically significant bleeding or sequestration or drug induced anemia, hemolytic anemia, or bleeding events.
• Clinically significant cardiovascular disease defined as:
• New York Heart Association heart disease class III or IV
• Fridericia corrected QT (QTcF) interval \>500 milliseconds during screening
• Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening
• Known ejection fraction \<35%, confirmed by a local echocardiogram performed during screening, or a previously performed echocardiogram if collected within 6 months before screening.
• Medical history of thromboembolic events within 6 months before screening, including history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism, arterial thrombosis or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
• Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
• Prior history of malignancies, other than MDS. Participants who are free of other malignant disease for ≥3 years and have completed treatment, including maintenance are allowed. Participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy:
• Basal or squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix;
• Carcinoma in situ of the breast;
• Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis \[TNM\] clinical staging system).
• History of solid organ or bone marrow transplantation.
• Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before randomization.
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
• Body mass index ≥ 40 kilograms per square meter (kg/m\^2).
• Major surgery within 28 days before randomization.
• New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization are excluded from trial participation.
• History of allergy/anaphylaxis to investigational product (including epoetin alfa) excipients (refer to the current elritercept investigator's brochure for a list of excipients) or recombination proteins.
• History of pure red cell aplasia and/or antibody against erythropoietin (EPO).
• Any of the following laboratory abnormalities:
• ANC \<500/microliter (μL) (0.5×109/L).
• Platelet count \<50,000/μL (50×109/L) or ≥450,000/μL (450×109/L).
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3× upper limit of the normal (ULN).
• Total bilirubin ≥2×ULN. Participants with known history of Gilbert syndrome with unconjugated bilirubin \<3×ULN are allowed. Higher levels if attributed to active RBC precursor destruction within the bone marrow (ineffective erythropoiesis) may be allowed upon medical monitor review.
• Estimated glomerular filtration rate \<30 mL/min/1.73 m\^2 as determined by the Chronic Kidney Disease Epidemiology (CKD-EPI) collaboration equation.
• Ferritin ≤50 micrograms per liter (μg/L).
• Folate ≤2.0 nanograms per milliliter (ng/mL).
• Vitamin B12 ≤200 picograms per milliliter (pg/mL).
• Ongoing participation in another interventional clinical trial.
• Participant is unwilling or in the opinion of the investigator the participant is unable to comply with the requirements of the protocol.
• Is a participant of childbearing potential (POCBP) but does not agree to use at least 1 form of highly effective contraception from the time of signing the ICF until at least 60 days after the last dose of trial intervention.
• Participants of male birth who are fertile and who have partners of childbearing potential, who do not agree to use acceptable barrier contraception, that is, a male condom during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
• If applicable, participant with a positive serum pregnancy test during the screening period or known to be pregnant or a lactating participant who does not agree to forego breastfeeding during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
• For Participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults.
DRUG: Elritercept, DRUG: Epoetin Alfa
Myelodysplastic Syndrome, Anemia
TAK-226, Drug therapy
A Hospital-based Intervention for Youth Injured Through Violence
Terri Sulivan - tnsulliv@vcu.edu
NCT07475247
Youth participant inclusion criteria:
* Aged 13-17 years old
* English speaking
Youth participant exclusion criteria:
* Youth aged \<13 years and \>17 years old
* Non-English speaking
* Youth of caregivers younger than 18 years old
Adult/caregiver participant inclusion criteria:
\- Aged 18 years or older
Adult/caregiver participant exclusion criteria:
\- Aged younger than 18 years
OTHER: Elevate Virtual Reality (VR), OTHER: Assessement completion
Violence
Virtual Reality, Fire-arm violence among youth
Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer
ctrrecruit@vcu.edu
NCT06980038
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed American Joint Committee on Cancer (AJCC) stage III-IV T0-4, N0-3b, M0 mucosal head and neck squamous cell carcinoma (HNSCC) (oral cavity, oropharynx, larynx, hypopharynx, and nasal cavity) that is appropriate for surgical resection. Both previously untreated (primary) and recurrent (salvage) settings will be eligible. Tumors must be accessible to biopsy in clinic (patients with laryngeal, hypopharyngeal, nasal cavity and base of tongue tumors will have endoscopic biopsies)
* For patients with oropharyngeal cancer, only p16-negative (non-human papillomavirus \[HPV\] related) patients will be eligible
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam
* Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of cemiplimab (REGN2810) alone or in combination with CDX-1140 in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
* Hemoglobin (Hb) ≥ 7 g/dL (transfusion allowed to bring Hb to this level)
* Absolute neutrophil count ≥ 1,000/mcL
* Platelets ≥ 100,000/mcL
* Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN
* Creatinine ≤ 1.5 × institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* Based on its mechanism of action, cemiplimab (REGN2810) can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Women of childbearing potential and men should use effective contraception during treatment with cemiplimab (REGN2810) and for 4 months after the last dose. The reproductive and developmental toxicity of CDX-1140 has not been evaluated. Women of childbearing potential and their partners who receive CDX-1140 must therefore take adequate contraceptive measures
* Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
Exclusion Criteria:
* Active or documented history of autoimmune disease within 2 years before screening
* Prior or planned allogeneic hematopoietic stem cell transplantation (HSCT)
* History of organ transplant that requires use of immunosuppressive medications
* Current or prior use of immunosuppressive medication within 14 days prior to the start of study drug administration. Immunosuppressants may interfere with study drug efficacy
* Any previous treatment with a PD-1 or PD-L1 inhibitor, including cemiplimab (REGN2810). It is unclear how prior exposure to immunotherapy would impact future use of checkpoint inhibitors
* Concurrent use of prednisone (10 mg or more)
* Patients with new pulmonary infiltrates indicative of pneumonitis, history of (non-infectious) pneumonitis/interstitial lung disease, or current pneumonitis/interstitial lung disease, including grade 1 pneumonitis (i.e., asymptomatic, clinical or diagnostic observation only, intervention not indicated)
* Another active malignancy for which the natural history or treatment has potential to interfere with the safety or efficacy assessment of the investigational regimen on this trial
* Patients who have not recovered from AE due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
* Patients who are receiving any other investigational agents, such as concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1140 or cemiplimab (REGN2810)
* Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
* Pregnant women are excluded from this study because of the increased risk of immune-mediated rejection of the developing fetus with cemiplimab (REGN2810). Because of the potential for serious adverse reactions in breastfed children, women should not breastfeed during treatment with cemiplimab (REGN2810) and for at least 4 months after the last dose. These risks may also apply to CDX-1140 BIOLOGICAL: Anti-CD40 Agonist Monoclonal Antibody CDX-1140, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Cemiplimab, PROCEDURE: Computed Tomography, PROCEDURE: Positron Emission Tomography, PROCEDURE: Tumor Resection
Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Nasal Cavity Squamous Cell Carcinoma, Oral Cavity Squamous Cell Carcinoma, Oropharyngeal Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Nasopharyngeal Carcinoma AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IVA Laryngeal Cancer AJCC v8, Stage IVA Lip and Oral Cavity Cancer AJCC v8, Stage IVA Nasopharyngeal Carcinoma AJCC v8, Stage IVB Laryngeal Cancer AJCC v8, Stage IVB Lip and Oral Cavity Cancer AJCC v8
Clinical Trial of N-803 Plus Tislelizumab or Prior Failed Immune Checkpoint Inhibitor and Docetaxel Versus Docetaxel Monotherapy in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Acquired Resistance to Immune Checkpoint In
Phillip Trieu - Phillip.Trieu@immunitybio.com
NCT06745908
Eligibility Criteria:
Women and men of all races and ethnic groups are eligible for this trial.
Cohort A
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Pathologically confirmed stage IV NSCLC disease.
• Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• Participants with AGA must have 1 or more documented AGA(s): EGFR, ROS1, neurotrophic tyrosine receptor kinase (NTRK), B rapidly accelerated fibrosarcoma (BRAF), mesenchymal epithelial transition (MET) exon 14 skipping, rearranged during transfection (RET), Kirsten Rat sarcoma (KRAS) and HER2.
• Participants with AGA must meet the following criteria for advanced or metastatic NSCLC. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved (and is standard of care) for the participant's genomic alteration at the time of screening:
• Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior osimertinib.
• Participants who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose or received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
• Participants who have been treated with a prior tyrosine kinase inhibitor (TKI) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
• Participants must also meet the inclusion criteria #4 listed above.
• ECOG performance status of 0 to 2.
• Measurable tumor lesions according to RECIST v1.1.
• Have a life expectancy of at least 3 months.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screening and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 7 months post last dose of study drug.
• Participants with known HIV infection must be receiving anti retroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.
• Systemic autoimmune disease currently requiring treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The participant must have been off treatment for 180 days.
• History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• Participants with AGA of ALK.
• History of known active hepatitis B or C infection to be assessed within 6 months prior to enrollment using locally accepted standard of care measurements. (Resolved cases are allowed.)
• Active infection requiring antibiotic therapy.
• Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• Body weight ≤ 40 kg at screening.
• Active treatment with CYP3A4 inhibitors.
• Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Participants with known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• Had major surgery within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating Investigator.
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute lymphocyte count \< institutional lower limit of normal (LLN) (ie, participant should have a normal lymphocyte count to enroll in the study).
• Absolute neutrophil count ≤ 1,500 cells/mm3.
• Platelet count ≤ 100,000 cells/mm3.
• Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × upper limit of normal (ULN) or direct bilirubin is \> ULN.
• Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN.
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN.
• Hemoglobin \< 9.0 g/dL.
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L or creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below): Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• Have any of following:
• Cirrhosis at a level of Child-Pugh B (or worse);
• Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• Participation in an investigational drug study within 21 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• Pregnant and nursing women.
• History of allergic reactions to tislelizumab.
• History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• Confinement in an institution by order of a court or authority. Cohort B
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Pathologically confirmed stage IV NSCLC disease.
• Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• Participants who receive an immune CPI as consolidation therapy after chemoradiation are eligible if they show progression or recurrence within 3 months of their last CPI and must have received at least 6 months of exactly 1 line of prior CPI therapy. If that CPI is not approved for advanced NSCLC, then an approved alternative CPI will be used.
• If participants are positive for actionable genomic alteration (AGA), defined as a genomic alteration which has at least 1 regional Health Authority-approved targeted therapy. Participants MUST have received at least 1 targeted therapy or 2 or more if multiple lines of targeted therapies are approved in the region. Thus, participants must have exhausted regional Health Authority-approved targeted therapies for their specific AGA for first- or second-line NSCLC, then have acquired resistance to immune checkpoint therapy to be eligible. Participants must meet inclusion criteria #4.
• Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Participants with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a site of disease.
• ECOG performance status of 0 to 2.
• Measurable tumor lesion(s) according to RECIST v1.1.
• Have a life expectancy of at least 3 months.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screening and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 7 months post last dose of study drug.
• Participants with known HIV infection must be receiving antiretroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.
• Autoimmune disease currently requiring systemic treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma) except for autoimmune thyroiditis needing thyroid replacement and diabetes requiring insulin. The participant must have been off treatment for 60 days.
• History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring active treatment with systemic steroids or other systemic therapy; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• Have an active or uncontrolled hepatitis B and/or hepatitis C infection and are positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomization. Participants are eligible if they:
• Have received hepatitis B vaccination with only anti-HBs positivity and no clinical signs of hepatitis.
• Have HbsAg+ with HBV infection for more than 6 months (ie, chronic HBV infection) meeting the following conditions: i. HBV DNA viral load \< 2,000 IU/mL. ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT \< 3 ULN that are not attributable to HBV infection. iii. Start or maintain antiviral treatment if clinically indicated as per the Investigator. c. Have been curatively treated for hepatitis.
• Active infection requiring systemic antibiotic therapy (antiviral therapy is allowed).
• Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• Body weight ≤ 40 kg at screening.
• Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• Known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• Had major surgery, myocardial infarction, and/or cerebrovascular accident within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery or illness in the opinion of the treating Investigator.
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute lymphocyte count \< institutional LLN (ie, participant should have a normal lymphocyte count to enroll in the study).
• Absolute neutrophil count ≤ 1,500 cells/mm3.
• Platelet count ≤100,000 cells/mm3.
• Total bilirubin \> 1.5 times the ULN, unless the participant has documented Gilbert's syndrome). Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × ULN or direct bilirubin is \> ULN.
• Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN or \> 5 times ULN for participants with liver metastases.
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN, \> 5 times ULN for participants with known bone metastases.
• Hemoglobin \< 9.0 g/dL.
• Creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below): Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• Have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse);
• Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• Participation in an investigational drug study within 28 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• Pregnant and nursing women.
• History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• Have a history of malignancy other than NSCLC, except:
• Adequately resected non-melanoma skin cancer; or,
• Curatively treated in situ disease or
• Other curatively treated solid tumors, with no evidence of disease for ≥ 3 years; or
• Hormone sensitive cancers treated only with hormone therapy.
• Other antineoplastic therapies intended to treat cancer, including herbal medicines or other prohibited concurrent medication(s) within 28 days prior to the start of treatment in the study.
• Confinement in an institution by order of a court or authority.
Inclusion Criteria:
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.
• Pathologically confirmed stage IV NSCLC disease.
• Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• Participants with AGA must have 1 or more documented AGA(s): EGFR, ROS1, neurotrophic tyrosine receptor kinase (NTRK), B rapidly accelerated fibrosarcoma (BRAF), mesenchymal epithelial transition (MET) exon 14 skipping, rearranged during transfection (RET), Kirsten Rat sarcoma (KRAS) and HER2.
• Participants with AGA must meet the following criteria for advanced or metastatic NSCLC. Participants who have been treated with 1 or 2 prior lines of applicable targeted therapy that is locally approved (and is standard of care) for the participant's genomic alteration at the time of screening:
• Participants who have tumors with EGFR L858R or exon 19 deletion mutations must have received prior osimertinib.
• Participants who received a targeted agent as adjuvant therapy for early-stage disease must have relapsed or progressed while on the treatment or within 6 months of the last dose or received at least one additional course of targeted therapy for the same genomic alteration (which may or may not be same agent used in the adjuvant setting) for relapsed/progressive disease.
• Participants who have been treated with a prior tyrosine kinase inhibitor (TKI) must receive additional approved targeted therapy, if locally available and clinically appropriate, for the applicable genomic alteration, or the participant will not be allowed in the study.
• Participants must also meet the inclusion criteria #4 listed above.
• ECOG performance status of 0 to 2.
• Measurable tumor lesions according to RECIST v1.1.
• Have a life expectancy of at least 3 months.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screening and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 7 months post last dose of study drug.
• Participants with known HIV infection must be receiving anti retroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.
Exclusion Criteria:
• Systemic autoimmune disease currently requiring treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma). The participant must have been off treatment for 180 days.
• History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring treatment with systemic steroids; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• Participants with AGA of ALK.
• History of known active hepatitis B or C infection to be assessed within 6 months prior to enrollment using locally accepted standard of care measurements. (Resolved cases are allowed.)
• Active infection requiring antibiotic therapy.
• Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• Body weight ≤ 40 kg at screening.
• Active treatment with CYP3A4 inhibitors.
• Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).
• Participants with known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• Had major surgery within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating Investigator.
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute lymphocyte count \< institutional lower limit of normal (LLN) (ie, participant should have a normal lymphocyte count to enroll in the study).
• Absolute neutrophil count ≤ 1,500 cells/mm3.
• Platelet count ≤ 100,000 cells/mm3.
• Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × upper limit of normal (ULN) or direct bilirubin is \> ULN.
• Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN.
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN.
• Hemoglobin \< 9.0 g/dL.
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L or creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below): Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• Have any of following:
• Cirrhosis at a level of Child-Pugh B (or worse);
• Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• Participation in an investigational drug study within 21 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• Pregnant and nursing women.
• History of allergic reactions to tislelizumab.
• History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• Confinement in an institution by order of a court or authority. Cohort B
Inclusion Criteria:
• Age ≥ 18 years old.
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Pathologically confirmed stage IV NSCLC disease.
• Have acquired resistance to a regional Health Authority-approved immune plus platinum-based chemotherapy, defined as disease progression immediately following an initial response (of any duration) or stable disease (approximately 6 months duration \[± 2 weeks\]). Participants who received anti-PD-1/anti-PD-L1 mAb as first-line therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 mAb in the second line. Participants must have received platinum chemotherapy to be eligible. Participants must have received anti-PD-1/anti-PD-L1 mAb in their immediate prior line of therapy to be eligible.
• Participants who receive an immune CPI as consolidation therapy after chemoradiation are eligible if they show progression or recurrence within 3 months of their last CPI and must have received at least 6 months of exactly 1 line of prior CPI therapy. If that CPI is not approved for advanced NSCLC, then an approved alternative CPI will be used.
• If participants are positive for actionable genomic alteration (AGA), defined as a genomic alteration which has at least 1 regional Health Authority-approved targeted therapy. Participants MUST have received at least 1 targeted therapy or 2 or more if multiple lines of targeted therapies are approved in the region. Thus, participants must have exhausted regional Health Authority-approved targeted therapies for their specific AGA for first- or second-line NSCLC, then have acquired resistance to immune checkpoint therapy to be eligible. Participants must meet inclusion criteria #4.
• Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Participants with asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a site of disease.
• ECOG performance status of 0 to 2.
• Measurable tumor lesion(s) according to RECIST v1.1.
• Have a life expectancy of at least 3 months.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Agreement to practice effective contraception for female participants of child-bearing potential and nonsterile males. Female participants of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Female participants of childbearing potential must have a negative serum pregnancy test at screening and adhere to using a highly effective method of contraception (eg, tubal ligation, approved hormonal contraceptive associated with inhibition of ovulation, or an intrauterine device \[IUD\]) prior to screening and agree to continue its use during the study or be surgically sterilized (eg, hysterectomy) while on study and for 7 months post last dose of study drug. Male participants must agree to use barrier methods of birth control while on study and for 7 months post last dose of study drug.
• Participants with known HIV infection must be receiving antiretroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to enrollment.
Exclusion Criteria:
• Autoimmune disease currently requiring systemic treatment (eg, lupus erythematosus, rheumatoid arthritis, Addison's disease, or autoimmune disease associated with lymphoma) except for autoimmune thyroiditis needing thyroid replacement and diabetes requiring insulin. The participant must have been off treatment for 60 days.
• History of any of the following: drug-induced severe cutaneous adverse reaction (SCAR), including, but not limited to Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), or dose-limiting immune-mediated reactions.
• History of allogeneic hematopoietic stem cell transplant or organ transplant requiring immunosuppression; or history of pneumonitis or interstitial lung disease requiring active treatment with systemic steroids or other systemic therapy; or a history of receiving systemic steroid therapy or any other immunosuppressive medication ≤ 3 days prior to study initiation. Daily steroid replacement therapy (eg, prednisone or hydrocortisone) and corticosteroids used to manage AEs are permitted.
• Have an active or uncontrolled hepatitis B and/or hepatitis C infection and are positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis B surface antigen \[HBsAg\], anti-hepatitis B surface antibody \[anti-HBs\], anti-hepatitis B core antibody \[anti-HBc\], or hepatitis B virus \[HBV\] DNA), and/or hepatitis C infection (as per hepatitis C virus \[HCV\] RNA) within 28 days of randomization. Participants are eligible if they:
• Have received hepatitis B vaccination with only anti-HBs positivity and no clinical signs of hepatitis.
• Have HbsAg+ with HBV infection for more than 6 months (ie, chronic HBV infection) meeting the following conditions: i. HBV DNA viral load \< 2,000 IU/mL. ii. Have normal transaminase values, or, if liver metastases are present, abnormal transaminases with a result of AST/ALT \< 3 ULN that are not attributable to HBV infection. iii. Start or maintain antiviral treatment if clinically indicated as per the Investigator. c. Have been curatively treated for hepatitis.
• Active infection requiring systemic antibiotic therapy (antiviral therapy is allowed).
• Have known active central nervous system (CNS) metastases, carcinomatous meningitis, and/or spinal cord compression.
• Body weight ≤ 40 kg at screening.
• Received a live vaccine ≤ 4 weeks prior to the first dose of study drug(s).
• Known history of severe hypersensitive reactions to docetaxel or to other drugs formulated with polysorbate 80.
• Had major surgery, myocardial infarction, and/or cerebrovascular accident within 28 days prior to study randomization. Participants must have fully recovered from the effects of prior surgery or illness in the opinion of the treating Investigator.
• Inadequate organ function, evidenced by the following laboratory results:
• Absolute lymphocyte count \< institutional LLN (ie, participant should have a normal lymphocyte count to enroll in the study).
• Absolute neutrophil count ≤ 1,500 cells/mm3.
• Platelet count ≤100,000 cells/mm3.
• Total bilirubin \> 1.5 times the ULN, unless the participant has documented Gilbert's syndrome). Participants with documented Gilbert's syndrome are to be excluded if total bilirubin is ≥ 3 × ULN or direct bilirubin is \> ULN.
• Aspartate aminotransferase (AST \[serum glutamic-oxaloacetic transaminase; SGOT\]) or alanine aminotransferase (ALT \[serum glutamic pyruvic transaminase; SGPT\]) \> 1.5 × ULN or \> 5 times ULN for participants with liver metastases.
• Alkaline phosphatase (ALP) levels \> 2.5 × ULN, \> 5 times ULN for participants with known bone metastases.
• Hemoglobin \< 9.0 g/dL.
• Creatinine clearance \< 40 mL/min (using the Cockcroft-Gault formula below): Female = \[(140 - age in years) × weight in kg × 0.85\] / \[72 × serum creatinine in mg/dL\] Male = \[(140 - age in years) × weight in kg × 1.00\] / \[72 × serum creatinine in mg/dL\]
• Have any of the following:
• Cirrhosis at a level of Child-Pugh B (or worse);
• Cirrhosis (any degree) and a history of hepatic encephalopathy; or
• Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• Participation in an investigational drug study within 28 days prior to the start of treatment on this study, except for hormone lowering therapy in participants with hormone-sensitive cancer. Participating in any other interventional clinical trial during active participation in this clinical trial is not allowed.
• Assessed by the Investigator to be unable or unwilling to comply with the requirements of the protocol.
• Pregnant and nursing women.
• History of prior adverse reaction to immunotherapy that led to its permanent discontinuation.
• Have a history of malignancy other than NSCLC, except:
• Adequately resected non-melanoma skin cancer; or,
• Curatively treated in situ disease or
• Other curatively treated solid tumors, with no evidence of disease for ≥ 3 years; or
• Hormone sensitive cancers treated only with hormone therapy.
• Other antineoplastic therapies intended to treat cancer, including herbal medicines or other prohibited concurrent medication(s) within 28 days prior to the start of treatment in the study.
• Confinement in an institution by order of a court or authority.
DRUG: N-803, DRUG: Tislelizumab, DRUG: Docetaxel, DRUG: Prior failed checkpoint inhibitor
NSCLC Stage IV
Safety, Efficacy, and Pharmacokinetics of CSL889 in Adults and Adolescents With Sickle Cell Disease During Vaso-Occlusive Crisis
Trial Registration Coordinator - clinicaltrials@cslbehring.com
NCT06699849
Inclusion Criteria:
* At the time of informed consent:
* 18 years of age (adults); or
* 12 to less than (\<) 18 years of age (adolescents, where approved and when enrollment for adolescents has been opened by the sponsor, with the endorsement of the Independent Data Monitoring Committee \[IDMC\])
* Diagnosed with SCD (any genotype).
* Presented at the study site with a new acute VOC necessitating treatment with parenteral opioids.
Exclusion Criteria:
* VOC pain onset greater than (\>) 72 hours before administration of first parenteral opioid.
* Must not have a history of \> 5 VOCs requiring hospital admission in the past 6 months; or signs and / or symptoms of ACS; or new neurological symptoms suggestive of acute stroke or transient ischemic attack; or any stage (acute kidney injury) AKI; or been discharged from inpatient hospital admission for VOC or other vaso-occlusive event within 14 days before the current presentation.
* Serum hemoglobin \< 6 g/dL, serum ferritin ≥ 2000 ng/mL, receiving an approved medication for SCD that has not been on a stable, well-tolerated regimen, currently taking methadone or buprenorphine. BIOLOGICAL: CSL889, DRUG: Placebo
Sickle Cell Disease Vaso-occlusive Crisis
Sickle cell disease, Acute kidney injury, Pharmacokinetics, Acute chest syndrome, Vaso-occlusive crisis, Hemopexin
Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study
ctrrecruit@vcu.edu
NCT06769126
Inclusion Criteria:
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have a history of limited stage small cell lung cancer
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must meet 1 of the following criteria prior to step 1:
* Treatment naïve and planning to receive frontline induction treatment with platinum plus etoposide in combination with durvalumab, OR,
* Have initiated frontline induction therapy and completed at least 1 (≥ 1) cycle and at most 3 (≤ 3) cycles of platinum and etoposide. At most 2 (≤ 2) of these cycles could have been given without durvalumab
* NOTE: Participants must not have received immunotherapy other than durvalumab (e.g., atezolizumab) prior to enrollment
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received any anti PD-1 or anti PD-L1 (including durvalumab \[MEDI4736\]) treatment for SCLC prior to starting frontline induction treatment for ES-SCLC
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received anti PD-1 or anti PD-L1 other than durvalumab (MEDI4736) as part of frontline induction treatment for ES-SCLC. Participants must have not received atezolizumab, pembrolizumab, or nivolumab as part of frontline induction treatment
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received any investigational agent for the treatment of ES-SCLC
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for SCLC treatment while receiving treatment on this study
* NOTE: If participant has bone metastases, bisphosphonates are allowed
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have any unresolved toxicity National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade ≥ 2 from previous anticancer therapy with the exception of alopecia, and vitiligo
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must be ≥ 18 years old at the time of step 1 registration
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must be able to safely receive the frontline induction treatment with platinum plus etoposide in combination with durvalumab, per the current Food and Drug Administration (FDA)-approved package insert(s), institutional guidelines, and the treating investigator's discretion
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must have Zubrod performance status of 0-2 within 28 days prior to step 1 registration
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator within 28 days prior to step 1 registration
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have had an allogenic organ transplantation
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must have adequate tumor tissue available from SCLC and agree to have these tissue specimens submitted. Participants must agree to have any leftover tissue (tissue that remains after subtype and biomarker testing) retained for the use of future correlative studies.
* NOTE: After a participant has been registered to step 1 registration, the tissue must be submitted to BostonGene. Sites will receive a notification from the Southwest Oncology Group (SWOG) Statistics and Data Management Center within 19 days after tissue submission. Patients must not be registered to step 2 prior to receiving notification of cohort assignment
* NOTE: A histologic review will be performed to confirm adequate cellularity for the testing. If inadequate cellularity, additional archival unstained slides from the same participant may be submitted if it does not exceed the window of starting maintenance therapy
* STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Site must have received notification from the SWOG Statistics and Data Management Center (SDMC) of the participant's SLFN11 testing results and have been determined to have subtype A, N, I, or P: confirmed by BostonGene and assigned to a cohort
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants may have measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and must have their disease assessed by CT of chest/abdomen/pelvis (with contrast unless contraindicated) within 28 days prior to step 2 for measurable disease or within 42 days prior to step 2 for non-measurable disease. All known sites of disease must be assessed and documented on the baseline tumor assessment form (RECIST 1.1). Any lesions assessed using a non-diagnostic PET/CT of chest/abdomen/pelvis will be considered non-measurable lesions
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to step 2 randomization. Participant must not have leptomeningeal disease, spinal cord compression, or symptomatic brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days following treatment, and prior to step 2 randomization, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to step 2 randomization
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants with untreated brain metastases must be asymptomatic and stable off steroids prior to step 2 randomization.
* NOTE: Exceptions to corticosteroid criterion are: (1) intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection), (2) systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, or (3) steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). Premedication with steroids for chemotherapy is acceptable
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must not have experienced disease progression in the opinion of treating investigator during induction treatment and prior to step 2
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have completed frontline induction therapy. Induction therapy must have included 4-6 cycles of platinum plus etoposide and 4 cycles of durvalumab (MEDI4736); at most 2 (≤ 2) cycles of platinum plus etoposide may have been given without durvalumab (MEDI4736). Durvalumab (MEDI4736) must have been given in combination with platinum plus etoposide
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants who received consolidation thoracic radiation therapy must have completed all radiation therapy at least 14 days prior to step 2
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: For participants not receiving consolidation thoracic radiation, step 2 registration must occur at least 3 weeks but not more than 6 weeks after the last dose of frontline induction therapy (platinum plus etoposide in combination with durvalumab \[MEDI4736\])
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: For participants receiving consolidation thoracic radiation after induction therapy, step 2 registration must occur at least 3 weeks but no more than 8 weeks after the last dose of frontline induction therapy (platinum plus etoposide in combination with durvalumab \[MEDI4736\])
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must not have received atezolizumab, pembrolizumab, or nivolumab as part of their frontline induction treatment. Participants must not have received prophylactic cranial irradiation (PCI)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have a complete medical history and physical within 28 days prior to step 2
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have body weight \> 30 kg
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have Zubrod performance status of 0-2 within 28 days prior to step 2
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Hemoglobin \> 9.0 g/dL (within 28 days prior to step 2)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to step 2)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Platelets ≥ 100 x 10\^3/uL (within 28 days prior to step 2)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to step 2)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 5 × institutional ULN (within 28 days prior to step 2)
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must have creatinine ≤ 1.5x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance ≥ 45 mL/min using the following Cockcroft-Gault Formula For creatinine clearance formula see the tools on the Cancer Research and Biostatistics (CRA) Workbench https://txwb.crab.org/TXWB/Tools.aspx
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to step 2 registration
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured or currently be receiving treatment for HVC. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must not have experienced the following during induction treatment: Any grade 3 or worse immune-mediated adverse event (irAE) (except asymptomatic nonbullous/nonexfoliative rash) or any unresolved grade 2 irAE, nor have experienced a toxicity that led to permanent discontinuation of prior durvalumab (MEDI4736). Toxicity of any grade that requires replacement therapy and has stabilized on therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must not have received a live or live attenuated vaccine within 30 days prior to step 2. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and COVID-19 vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated, and are not allowed
* STEP 2: COHORT REGISTRATION AND MAINTENANCE RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking PROCEDURE: Biospecimen Collection, DRUG: Ceralasertib, PROCEDURE: Computed Tomography, BIOLOGICAL: Durvalumab, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Monalizumab, DRUG: Platinum Compound, PROCEDURE: Positron Emission Tomography, DRUG: Saruparib, RADIATION: Thoracic Radiation Therapy
Extensive Stage Lung Small Cell Carcinoma, Lung Small Cell Carcinoma, A Subtype, Lung Small Cell Carcinoma, I Subtype, Lung Small Cell Carcinoma, N Subtype, Lung Small Cell Carcinoma, P Subtype
Evaluating Whether an Educational Website Called Current Together After Cancer (CTAC) Improves Follow-up Care for Colorectal Cancer Survivors
ctrrecruit@vcu.edu
NCT07018869
Inclusion Criteria:
* PATIENTS:
* Patient participants must have newly diagnosed surgically resected, stage II or stage III colorectal cancer per the timing described below
* Patient participants must have an adult in their life who supports them in their colorectal cancer journey who they might be willing to invite to join them in viewing an educational website. This is determined via the question: "Do you have an adult in your life, such as a spouse/partner, family member or friend, who supports you with your colorectal cancer journey and may be willing to view a website with you? When we say, "supports you in your colorectal cancer journey", we mean things like, helping you keep and get to medical appointments, talking with you and/or your doctors about your cancer, or helping you make decisions about your cancer."
* Those who respond "no" to the question above will be told that "Because this study is for patients and a supporter to view the website together, you are not eligible for this study, but there may be other studies you are eligible for in the future".
* NOTE: The above question will be used to define "supporter" for purposes of this study. Examples of supporters include a spouse, partner, sibling, adult child, another family member, or friend.
* NOTE: The supporter does not have to agree to participate in the study in order for the patient to be eligible for this study. Justification for requiring the enrolled patient to have a supporter (whether the supporter is invited or participates) is based on the study's underlying conceptual framework
* Patient participants must not have recurrent or metastatic (stage IV) colorectal cancer
* Patient participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the efficacy assessment of this intervention
* Patient participants must be registered within 90 - 180 days of surgical resection
* Patient participants must be ≥ 18 years of age at the time of registration/randomization. The lower cutoff of 18 was determined because the lower age range of patients that may be recruited to Southwest Oncology Group (SWOG) studies is 18
* Patient participants must have Zubrod performance status of 0-2
* Patient participants must be able to read English or Spanish since the website for the intervention and control arm are available in English and Spanish
* Patient participants must: 1) be able to complete Patient Reported Outcome (PRO) questionnaires in English or Spanish, and 2) agree to complete PROs at all scheduled timepoints
* Patient participants will be encouraged to provide an email address or cell phone number, if possible, for the purpose of being contacted by staff at the University of Michigan who will provide access to the educational website. For those who do not wish to provide or create an email address or a cell phone number, they may still participate with alternate methods
* Patient participants must not be enrolled or be planning to enroll in a clinical trial of investigational treatment that includes imaging and/or laboratory monitoring for the duration of this trial
* NOTE: Patient participants are allowed to be co-enrolled on other non-treatment clinical trials
* SUPPORTER PARTICIPANT:
* Supporter participants must be ≥ 18 years of age at the time of registration/randomization
* Supporter participants must be able to read English or Spanish since the educational website is available in English and Spanish
* Supporter participants must have been identified by the patient as a person who may be willing to join them in reviewing the educational website
* PATIENT AND SUPPORTER:
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Patient and supporter participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. This protocol does not permit use of Legally Authorized Representative OTHER: Intervention website access, OTHER: Control website access, OTHER: Interview, OTHER: Questionnaire Administration
Colorectal Cancer Stage II, Colorectal Cancer Stage III
Study of ISB 2001 in Relapsed/Refractory Multiple Myeloma (TRIgnite-1)
Ichnos Sciences Clinical Trials Administrator - clinicaltrials@ichnossciences.com
NCT05862012
Inclusion Criteria:
• Participants with pathologically confirmed MM with measurable M-protein: serum and/or 24 hour urine, serum-free light chains or measurable isolated plasmacytoma
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
• Must have adequate hematologic, hepatic, renal, and cardiac functions
Exclusion Criteria:
• Active malignant central nervous system involvement
• Uncontrolled infection requiring systemic antibiotic therapy or other serious infection prior to C1D1
• History of autoimmune disease requiring systemic immunosuppressive therapy
• Any concurrent or uncontrolled medical, comorbid, psychiatric or social condition that would limit compliance with study procedures, interfere with the study results, substantially increase the risk of AEs, compromise ability to provide written informed consent or, in the opinion of the Investigator, constitute a hazard for participating in this study.
• Female subjects who are lactating and breastfeeding or have a positive pregnancy test during the screening period or on Day 1 before first dose of ISB 2001.
DRUG: ISB 2001, DRUG: ISB 2001
Relapsed/Refractory Multiple Myeloma
ISB 2001, Relapsed/refractory multiple myeloma, Open-label, Dose escalation, Dose expansion
Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer
ctrrecruit@vcu.edu
NCT07198074
Inclusion Criteria:
* Documentation of disease:
* Stage III and stage IVA endometrial cancers (with measurable disease),
* Stage IVB endometrial cancer (with or without measurable disease), or
* Recurrent endometrial cancer (with or without measurable disease)
* In patients with measurable disease, lesions will be defined and monitored by RECIST 1.1. Measurable disease (RECIST 1.1) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI
* Histologic confirmation of the original primary tumor is required (submission of pathology report\[s\] is required). Patients with the following histologic types are eligible: endometrioid, serous, dedifferentiated/undifferentiated, clear cell, mixed epithelial, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.)
* Patients must have:
* Tumoral mismatch repair proficient (pMMR) disease as assessed by immunohistochemistry (IHC) AND
* P53 IHC with aberrant staining pattern (aberrant p53 expression is consistent with mutant TP53). TP53 mutation by next-generation sequencing will also be accepted
* A pathology report demonstrating results of institutional MMR IHC and p53 IHC and/or TP53 by next-generation sequencing
* Patients may have received:
* NO prior chemotherapy for treatment of endometrial cancer OR
* Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\]) provided adjuvant chemotherapy was completed ≥ 12 months prior to registration
* Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to registration. For patients with recent radiation, they must have RECIST-evaluable disease outside of the radiation field and have recovered their marrow function
* Patients may have received prior hormonal (endocrine) therapy. All hormonal (endocrine) therapy must have been completed at least 1 week prior to registration
* NO prior pembrolizumab (or other anti-PD1, anti-PDL1 or anti-CTLA4 therapy) or bevacizumab (or other antiangiogenic therapy)
* Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dl
* Creatinine clearance (CrCl) of ≥ 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* No active infection requiring parenteral antibiotics
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No clinically significant bleeding within 28 days prior to registration
* No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg
* No major surgery within 28 days of initiation of bevacizumab
* No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease
* Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
* Topical or inhaled steroids are allowed
* Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), and anti-thyroid antibodies should be evaluated with the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* No history of stem cell or solid organ transplant
* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients) BIOLOGICAL: Bevacizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab
Advanced Endometrial Carcinoma, Recurrent Endometrial Carcinoma
Study of Izalontamab Brengitecan (BMS-986507) Versus Platinum-Pemetrexed for EGFR-mutated Non-small Cell Lung Cancer After Failure of EGFR TKI Therapy (IZABRIGHT-Lung01)
BMS Clinical Trials Contact Center www.BMSClinicalTrials.com - Clinical.Trials@bms.com
NCT07100080
Inclusion Criteria:
* Non-squamous NSCLC, not amenable to treatment in curative intent.
* Documented evidence of EGFR mutation (exon 19 deletion, L858R mutation).
* Progressive disease on a 3rd-generation (such as osimertinib, furmonertinib, lazertinib,...) EGFR-TKI-based mono- or combination therapy regimen as the most recent line of therapy in an adjuvant, locally advanced, or metastatic treatment setting.
* Eligible to receive a platinum-based doublet chemotherapy regimen (either cisplatin or carboplatin in combination with pemetrexed).
Exclusion criteria:
* Inadequate organ function and/or bone marrow reserve.
* Leptomeningeal metastases or spinal cord compression.
* Poorly controlled systemic medical conditions.
* Other protocol-defined inclusion/exclusion criteria apply. DRUG: Iza-bren, DRUG: Carboplatin, DRUG: Cisplatin, DRUG: Pemetrexed
Non-small Cell Lung Cancer
Epidermal Growth Factor Receptor, Tyrosine Kinase Inhibitors, Osimertinib, Standard of Care, Lung Neoplasms, Antineoplastic Agents, Izalontamab brengitecan, Iza-bren, BL-B01D1, Carboplatin, Cisplatin, Pemetrexed
Testing the Addition of Docetaxel (Chemotherapy) to the Usual Treatment (Hormonal Therapy and Apalutamide) for Metastatic Prostate Cancer, ASPIRE Trial
Shiva Baghaie, MPH - GUprotocols@alliancenctn.org
NCT06931340
Inclusion Criteria:
* Documentation of disease:
\* Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology
* Must have had evidence of metastatic disease (American Joint Committee on Cancer \[AJCC\] metastasis \[M\]1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
* Bone metastases detected by CT, radionuclide technetium-99 (99Tc)- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria; OR
* Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥ 15 mm) detected on CT or MRI as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Subjects with regional lymph node metastases only (nodes \[N\]1, below the aortic bifurcation) will not be eligible for the study; OR
* Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥ 10 mm
* Evidence of metastatic disease by PSMA-PET only and not visible by CT, radionuclide bone scan, or MRI will not satisfy eligibility criteria
* No metachronous low-volume disease (defined as recurrent metastatic disease after definitive treatment of prostate primary) and with ≤ 4 bone metastasis and no visceral metastasis on conventional imaging by CT, radionuclide 99Tc-biphosphonate bone scan, or MRI)
* Next generation sequencing (NGS) results from any tissue based Clinical Laboratory Improvement Act (CLIA) test must be available at the time of registration. NGS from soft tissue or visceral lesion if available is preferred. NGS from bone or primary prostate will be accepted. Patients with failed NGS testing are not eligible
* Prior treatment
* ADT (luteinizing hormone-releasing hormone \[LHRH\] agonist/antagonist or orchiectomy) with or without first generation anti-androgen, or second-generation androgen receptor signaling inhibitor (ARSI) within 120 days of registration is permitted. No washout period will be needed for the first generation- androgen or ARSI prior to registration. Anti-androgen treatment is only permitted if used within 120 days of registration
* No prior chemotherapy for prostate cancer
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Absolute neutrophil count (ANC) ≥ 1,500/mm\^3
* Hemoglobin ≥ 9.0 g/dL
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 1 x upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤ 1 × ULN, subject may be eligible)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate transaminase \[SGT\]) ≤ 1.5 x upper limit of normal (ULN)
* Calculated (Calc.) creatinine clearance \> 30 mL/min
* Serum potassium ≥ 3.5 mmol/L
* Comorbid conditions
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Leptomeningeal metastases: Patients with treated leptomeningeal metastases are eligible if follow-up brain imaging 30 days after central nervous system (CNS)-directed therapy shows no evidence of progression
* HIV: Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* No seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year to randomization, brain arteriovenous malformation or condition requiring CNS surgery or radiation therapy)
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class II or better. Any condition that in the opinion of the investigator, would preclude participation in this study. Patients with stable asymptomatic deep venous thromboembolism on stable anti-coagulation will be eligible
* Hypertension: Subjects with uncontrolled hypertension as indicated by a resting systolic blood pressure (BP) \>= 160 mmHg or diastolic BP \>= 100 mmHg despite medical management are not permitted to register
* Allergies: Subjects with known hypersensitivity to any of the study drugs, or excipients in the formulation of the study drugs are not permitted to register
* Concomitant medications
* Chronic concomitant treatment with strong inhibitors of cytochrome P450 3A4 (CYP3A4) is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration on the study. See Section 8.1.9 for more information
* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* Medications known to lower the seizure threshold must be discontinued or substituted prior to study entry. See Section 8.1.9 for more information
* Patient agrees to use a condom (even men with vasectomies) and another effective method of birth control if having sex with a woman of childbearing potential or agrees to use a condom if having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug. Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug DRUG: Androgen Therapy, DRUG: Apalutamide, DRUG: Docetaxel, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Bone Scan, PROCEDURE: PSMA PET Scan, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Castration-Sensitive Prostate Carcinoma, Metastatic Prostate Adenocarcinoma, Stage IVB Prostate Cancer AJCC v8
Symbiotic-Lung-20: A Study to Learn About the Study Medicine Called PF-08634404 in Combination With Different Anticancer Agents in Advanced Cancers
Pfizer CT.gov Call Center - ClinicalTrials.gov_Inquiries@pfizer.com
NCT07227298
Inclusion Criteria:
* Pathologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) squamous or non-squamous NSCLC and are not a candidate for complete surgical resection and curative concurrent/sequential chemoradiotherapy
* PD-L1 status available
* Part B only: PD-L1 ≥ TPS 1%
* Measurable disease based on RECIST v1.1 per investigator.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* Adequate organ function
Exclusion Criteria:
* Participants with known AGAs including EGFR, ALK and ROS1, NTRK, BRAF, and MET
* History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy
* Known active CNS lesions, including brainstem, meningeal, or spinal cord metastases or compression
* Leptomeningeal disease
* Active autoimmune diseases requiring systemic treatment within the past 2 years
* Previous systemic anti-tumor therapy for locally advanced, unresectable, or metastatic NSCLC
* Previous treatment with immunotherapy (exception is (neo)adjuvant anti-PD-(L)1), ADCs containing MMAE payload, systemic anti-angiogenic therapy, or prior radiotherapy to the lung within 6 months of first dose of study intervention BIOLOGICAL: PF-08634404, BIOLOGICAL: Sigvotatug Vedotin, BIOLOGICAL: Combination Agent 1
Advanced/Metastatic Non-Small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, Non-small Cell Lung Cancer
non-small cell lung cancer, NSCLC, advanced solid tumors, metastatic non-small cell lung cancer, locally advanced non-small cell lung cancer, squamous non-small cell lung cancer, non-squamous non-small cell lung cancer
Ketamine add-on Therapy for Established Status Epilepticus Treatment Trial (KESETT) (KESETT)
Megan Wardius - mew5j@virginia.edu
NCT06907173
Inclusion Criteria:
* The patient was witnessed to have a convulsive seizure for greater than 5-minute duration
* The patient received an adequate dose of benzodiazepines. The doses may be divided.
* The last dose of a benzodiazepine was administered 5-30 minutes before study drug administration.
* Continued or recurring seizures in the Emergency Department.
* Age 1 years or older
* Known or estimated weight ≥10 Kg
Exclusion Criteria:
* Known pregnancy
* Prisoner
* Opt-out identification or otherwise known to be previously enrolled in KESETT
* Treatment with a second line anticonvulsant (FOS, PHT, VPA, LEV, phenobarbital, or other agents defined in the MoP) for this episode of SE
* Treatment with sedatives with anticonvulsant properties other than benzodiazepines for this episode of SE(propofol, etomidate, ketamine or other agents defined in the MoP)
* Endotracheal intubation prior to enrollment
* Acute traumatic brain injury clearly precedes seizures
* Scalp injury or burn preventing EEG placement
* Known allergy or other known contraindication to KET or LEV
* Hypoglycemia \< 50 mg/dL
* Hyperglycemia \> 400 mg/dL
* Cardiac arrest / post-anoxic seizures DRUG: Levetiracetam (LEV) (60 mg/Kg) + 1 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg) + 3 mg/kg Ketamine (KET), DRUG: Levetiracetam (LEV) (60 mg/Kg)
Status Epilepticus
Evaluating the Safety and Efficacy of dNerva Lung Denervation System in Patients With COPD (AIRFLOW-4)
John Carline - jcarline@nuvaira.com
NCT07051707
Inclusion Criteria:
* ≥ 40 and ≤ 80 years of age at the time of consent.
* Women of childbearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study.
* Smoking history of at least 10 pack years.
* Not smoking or using any other inhaled substance (e.g. cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study.
* Resting SpO2 ≥ 89% on room air.
* MMRC ≥ 2; CAT score ≥ 10.
* Diagnosis of moderate to severe COPD as defined by FEV1/FVC \< 70% (post-bronchodilator), 25% ≤ FEV1 ≤ 70% predicted, and PaCO2 \< 50 (if FEV1 \< 30%).
* RV ≥ 175% of predicted and RV/TLC \> 55% (post-bronchodilator).
* Participant is on standard medical care, defined as a minimum of therapy with LABA/ICS, LAMA/LABA, or LAMA/LABA/ICS for at least 2 months prior to consent.
* If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit; NOTE: Prior participation in a pulmonary rehabilitation program is not required for inclusion in the study.
* Participant is a candidate for bronchoscopy in the opinion of the investigator or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally.
* Participant is able and agrees to complete all protocol required baseline and follow up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone).
Exclusion Criteria:
* Body Mass Index (BMI) \<18 or \>32.
* Participant has an implantable electronic device and has not received appropriate medical clearance.
* Uncontrolled diabetes in the opinion of the investigator.
* 4 or more respiratory related hospitalizations within 1 year of consent.
* Malignancy treated with radiation or chemotherapy within 1 year of consent.
* Participant diagnosed with a dominant non-COPD lung disease, or condition affecting the lungs, which is the main driver of the participant's clinical symptoms (e.g., cystic fibrosis, paradoxical vocal cord motion, eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis, interstitial lung disease or active tuberculosis or Asthma) or has a documented medical history of pneumothorax within 1 year of consent.
* Clinically relevant bronchiectasis, defined as \> 1/3 cup mucous expectoration daily.
* Pre-existing diagnosis of pulmonary hypertension, clinical evidence of pulmonary hypertension (e.g., cardiovascular function impairment including peripheral edema) and mPAP ≥25 mmHg at rest by right heart catheterization (or estimated right ventricular systolic pressure \>50 mmHg by echocardiogram if no previous right heart catheterization).
* Myocardial infarction within last 6 months, evidence of life-threatening arrhythmias or acute ischemia, pre-existing documented evidence of a LVEF \< 40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure.
* Surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent, or ongoing related symptoms within the past year.
* Symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm). NOTE: Participants with a hiatal hernia are allowed if Participant meets all other enrollment criteria.
* Any disease or condition that might interfere with completion of a procedure or this study (e.g., structural esophageal disorder, life expectancy \<3 years).
* Prior lung or chest procedure (e.g., BLVR explant procedure, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent? Participants with lung transplant, BLVR valves, LVRS, metal stents within 5cm of the anticipated treatment location; presence of lung volume reduction valves, coils or other lung implants.
* Daily use of \>20 mg of prednisone or its equivalent at the time of consent.
* Known contraindication or allergy to medications required for bronchoscopy or general anesthesia (e.g., lidocaine, atropine, propofol, sevoflurane) that cannot be medically controlled.
* Baseline chest CT scan reveals bronchial anatomy cannot be treated with available catheter sizes; presence of whole lung emphysema \>20% (-950 HU), single lung emphysema \>26% (-950 HU), severe bullous disease (\>1/3 hemithorax) or discovery of a mass that requires treatment.
* Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up. DEVICE: Targeted Lung Denervation (TLD)
COPD, Chronic Obstructive Pulmonary Disease
Optimal Medical Care, Device: dNerva Lung Denervation System, Device: Targeted Lung Denervation (TLD)
A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease (PARAISO)
Reference Study ID Number: BN44715 https://forpatients.roche.com/ - global-roche-genentech-trials@gene.com
NCT07174310
Inclusion Criteria:
* Body weight within 40-110 kilograms (kg) (88-242 pounds \[lbs\]) and a body mass index within the range 18-34 kg/m2
* Diagnosis of idiopathic PD based on Movement Disorder Society (MDS) criteria
* Has received monotherapy treatment
* An MDS-UPDRS Part IV score of 0 at screening and prior to randomization
* Hoehn and Yahr (H\&Y) Stage 1 or 2 off medication at screening and prior to randomization
* Agreement to adhere to the contraception requirements
Exclusion Criteria:
* Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
* Medical history indicating a parkinsonian syndrome other than idiopathic PD
* Diagnosis of a significant neurologic disease other than PD
* Chronic uncontrolled hypertension DRUG: Prasinezumab, DRUG: Placebo
Parkinson's Disease
Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial)
ctrrecruit@vcu.edu
NCT06116682
Inclusion Criteria:
* Participants must have been assigned to S1900J by the Southwest Oncology Group (SWOG) Statistics and Data Management Center (SDMC). Assignment to S1900J is determined by the LUNGMAP protocol
* Participants must have documentation of NSCLC with MET amplification determined by FMI tissue-based next generation sequencing (NGS) assay
* Participants must have measurable disease documented by CT or MRI. The CT from a combined positron emission tomography (PET)/CT may be used to document measurable disease ONLY if it is of diagnostic quality: otherwise, it may be used to document non-measurable disease only. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to sub-study registration to be considered measurable
* Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration
* Participants with asymptomatic CNS metastasis (brain metastases or leptomeningeal disease) must be clinically stable and asymptomatic for at least 14 days prior to sub-study registration
* NOTE: Participants can be on a low-dose corticosteroid treatment (≤ 10 mg prednisone or equivalent) for at least 14 days prior to study treatment
* Participants must not have other known actionable oncogenic alterations, such as (but not limited to) EGFR sensitizing mutations, EGFR T790M mutation, MET Exon-14 skipping mutant NSCLC, ALK gene fusion, ROS1 gene rearrangement, RET gene rearrangement, NTRK rearrangement, HER2 mutation, KRAS activating mutations, and BRAF V600E mutation
* Participants must have progressed (in the opinion of the treating physician) following the most recent line of therapy
* Participants must have received at least one line of systemic treatment for Stage IV or recurrent NSCLC
* Participants must have recovered (≤ Grade 1) from any side effects of prior therapy. The exception is if a side effect from a prior treatment is known to be permanent without expected further recovery or resolution (i.e., endocrinopathy from immunotherapy or cisplatin neurotoxicity)
* Participants must not have been previously treated for any cancer with MET tyrosine kinase inhibitors (TKIs) such as tepotinib, capmatinib, and crizotinib
* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration
* Participants must not have a prior treatment with anti-PD-1 or anti-PD-L1 antibody within 6 weeks of sub-study registration
* Participants must not have received any radiation therapy within 14 days prior to sub-study registration
* Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
* Participants must not have had major surgery excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 28 days prior to sub-study registration, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study
* NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to sub-study registration)
* Hemoglobin \>= 10.0 g/dL (within 28 days prior to sub-study registration)
* Platelets ≥ 75 x 10\^3/uL (within 28 days prior to sub-study registration)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to sub-study registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional ULN. Participants with history of liver metastasis must have AST and ALT ≤ 5 x ULN (within 28 days prior to sub-study registration)
* Participants must have a serum creatinine ≤ the institutional upper limit of normal (IULN) or calculated creatinine clearance ≥ 45 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration. For creatinine clearance formula see the tools on the CRA Workbench
* Participants' most recent Zubrod performance status must be 0-2 and be documented within 28 days prior to sub-study registration
* Participants must have a completed medical history and physical exam within 28 days prior to sub-study registration
* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy and have undetectable viral load test on the most recent test results obtained within 6 months prior to sub-study registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to sub-study registration
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to sub-study registration
* Participants with known diabetes as determined by the treating investigator must show evidence of controlled disease within 14 days prior to sub-study registration
* Participants of reproductive potential must have a negative serum pregnancy test within 7 days prior to sub-study registration
* Participants must not have other clinically active infectious liver disease
* Participants must not have clinically significant hypertension within 28 days prior to sub-study registration as determined by the treating investigator
* Participants must not have a history of pneumonitis that required drug therapy or an active symptomatic interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis
* Participants must not have ongoing or active infection or be diagnosed or suspected viral infection as determined by the treating investigator. NOTE: Participants that have an infection requiring antimicrobial therapy will be required to complete antibiotics 1 week prior to starting treatment
* Participants must not have active bleeding diathesis as determined by the treating investigator
* Participants must not have impaired oxygenation requiring continuous oxygen supplementation as determined by the treating investigator
* Participants must not have psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements as determined by the treating investigator
* Participants must not have any ophthalmologic condition that is unstable in the opinion of the treating investigator
* Participants must not be pregnant or breastfeeding (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
* Participants must also be offered participation in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* NOTE: Participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations BIOLOGICAL: Amivantamab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging
Lung Non-Small Cell Carcinoma
Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays
Lilli Johnson - cancercontrolprotocols@allinancenctn.org
NCT07283939
Inclusion Criteria:
* \* REGISTRATION ELIGIBILITY CRITERIA (STEP 1)
* Histologic confirmation of invasive cancer that is confirmed or suspected to arise from the gastrointestinal (GI) tract
* Any stage for which FOLFOX-based chemotherapy is a clinically-indicated, standard-of-care treatment (adjuvant, neoadjuvant, or first-line chemotherapy)
* Eligible primary tumor sites include the esophagus, gastroesophageal junction, stomach, small intestine, ampulla of Vater, appendix, colon, rectum, and cancers of unknown primary with suspected GI origin
* Prior systemic therapy for GI cancer (other than cycle 1 of FOLFOX-based chemotherapy) is not allowed. Prior radiation-sensitizing chemotherapy is permitted
* The planned duration of FOLFOX-based chemotherapy must be at least four cycles (1 cycle = 14 days)
* Cycle 1, day 1 of FOLFOX-based chemotherapy must be completed 1 to 8 days prior to registration
* Cycle 1, day 1 of FOLFOX-based chemotherapy must include minimum ordered doses of oxaliplatin (≥ 65 mg/m\^2) and infusional 5-FU (2400 mg/m\^2/46 hours). Use of the 5-FU bolus is at the discretion of the treating physician
* Patients who require primary prophylactic white blood cell growth factor with cycle 1 of FOLFOX chemotherapy due to high risk for fever and neutropenia are not eligible
* History of hypersensitivity reaction to oxaliplatin or other platinum-based drugs, to fluorouracil, or to leucovorin, and the excipients in their formulations are not eligible
* Age ≥ 18 years
* ECOG performance status ≤ 2
* Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Total bilirubin ≤ 3 x upper limit of normal (ULN)
* AST (SGOT)/ALT (SGPT) ≤ 5 x upper limit of normal (ULN)
* Calc. creatinine clearance ≥ 30 mL/min
* Not pregnant and not nursing, because this study involves agents that have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 30 days prior to registration is required
* Patients with treated brain metastases are eligible if follow-up brain imaging after CNS-directed therapy shows no evidence of progression
* Patients with known HIV infection are eligible if receiving effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration
* Patients with known chronic hepatitis B virus (HBV) infection are eligible if HBV DNA is undetectable when measured within 6 months prior to registration
* Patients with a known history of hepatitis C virus (HCV) infection are eligible if HCV RNA is undetectable when measured at least 12 weeks after completion of antiviral therapy
* Patients with known history or current symptoms of cardiac disease are eligible if the New York Heart Association Functional Classification is class I or II
* Patients with a known history of congenital long QT syndrome are ineligible
* Patients with known DPD deficiency are ineligible
* \* NON-PATIENT (ONCOLOGY PHYSICIAN OR ONCOLOGY ADVANCED PRACTICE PROVIDER ELIGIBILITY:
* The non-patient provider participant is a medical oncologist or oncology advanced practice provider with responsibility for signing and making necessary modifications to chemotherapy orders for a subject assigned to the intervention arm (Arm B). Non-patient participants may not be enrolled more than once over the course of the study
* The non-patient participant must be proficient in the English language
* The non-patient participant must be age 21 years or older OTHER: PAGODA algorithm, DRUG: Oxaliplatin, DRUG: Folinic Acid, DRUG: Fluorouracil
Ampulla of Vater Carcinoma, Appendix Carcinoma, Carcinoma of Unknown Primary With Gastrointestinal Profile, Colon Carcinoma, Esophageal Carcinoma, Gastric Carcinoma, Gastroesophageal Junction Carcinoma, Malignant Digestive System Neoplasm, Rectal Carcinoma, Small Intestinal Carcinoma
A Study of Suvorexant (MK-4305) for the Treatment of Insomnia Disorder in Participants With Opioid Use Disorder (MK-4305-098)
Toll Free Number - Trialsites@msd.com
NCT06655883
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a primary diagnosis of OUD according to Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM-5), and confirmed through the Mini International Neuropsychiatric Interview (MINI).
* Is on a verified, stable dose of medications for opioid use disorder (MOUD) treatment.
* Meets DSM-5 criteria for the diagnosis of Insomnia Disorder
* Has a regular bedtime between 8 PM (20:00) and 1 AM (01:00) and is willing to maintain it for the duration of the study.
* Has not used opioids for a period of at least 4 weeks before entering the study.
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has current uncontrolled major co-morbid psychiatric illness including major depressive disorder, bipolar disorder, schizophrenia, or any psychiatric condition with psychotic features.
* Has current diagnosis or history within 5 years of any of the following: narcolepsy, sleep paralysis, severe periodic limb movement disorder, restless leg syndrome, cataplexy, circadian rhythm sleep disorder, parasomnia including nightmare disorder, sleep terror disorder, sleepwalking disorder, rapid eye movement (REM) behavior disorder, significant degree of sleep-related breathing disorder, excessive daytime sleepiness (EDS), or primary hypersomnia.
* Is at imminent risk of self-harm.
* Has a known history of stroke that may confound the diagnosis of insomnia.
* Has a clinically significant movement disorder such as akinesia.
* Has a history of hepatitis or live disease.
* Has habitual use of central nervous system (CNS)-depressants or stimulants that may be responsible for the participant's disturbed sleep.
* Has a history of malignancy, ≤3 years prior to start of study, with the exception of nonmelanoma skin cancer, prostate cancer or localized carcinoma in situ of the cervix.
* Has a history of hypersensitivity to more than 3 chemical classes of drugs, including prescription and over-the-counter medications.
* Has donated blood products or had phlebotomy within 8 weeks prior to start of study.
* Has a history of transmeridian travel within 2 weeks prior to start of study. DRUG: Suvorexant, DRUG: Placebo
Insomnia
Testing Whether High Dose Chemotherapy and Infusion of the Patients' Own Stem Cells Improves Survival in Patients With Peripheral T-cell Lymphoma Who Achieved a Complete Response at the End of the Initial Chemotherapy
Pamela Cogliano - ecog.rss@jimmy.harvard.edu
NCT06724237
Inclusion Criteria:
* Patient must be 18 to 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patient must have histologically proven peripheral T-cell lymphoma (PTCL) in one of the following categories:
* Anaplastic large cell lymphoma (ALCL) ALK-negative
* Angioimmunoblastic T-cell lymphoma (AITL)
* Nodal PTCL with follicular helper T cell (TFH) phenotype
* Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)
* Patient must have undergone induction treatment with an anthracycline based chemotherapy.
* NOTE: Patients who discontinued anthracycline during treatment are eligible as long as they received at least one dose and achieved complete remission
* Patient must have achieved radiologic complete remission following induction therapy as defined by the Lugano criteria with a Deauville score between 1-3 by PET-CT
* NOTE: There is no central review required. Confirmation of complete remission status is determined by the enrolling institution's review
* NOTE: If a patient had a positive bone marrow biopsy at the time of initial diagnosis (pre-induction), a repeat biopsy must be completed post induction to confirm complete remission (CR)
* Patient must be eligible for high dose chemotherapy and autologous stem cell transplant (ASCT) per the enrolling institutional guidelines at the transplant center and be ready to proceed with ASCT if randomized to the ASCT arm
* Patient must not have active infection requiring intravenous systemic antimicrobial at time of randomization. Antibiotic prophylaxis is acceptable as long as the dose of the medication has been stable for at least 7 days prior to randomization
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse during the treatment phase of the study and thereafter according to institutional guidelines
* Absolute neutrophil count (ANC) ≥ 1000/mcL (obtained ≤ 14 days prior to protocol randomization)
* Platelets ≥ 75,000/mcL (obtained ≤ 14 days prior to protocol randomization)
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3.0 x institutional ULN (obtained ≤ 14 days prior to protocol randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, OTHER: Best Practice, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: High Dose Chemotherapy, PROCEDURE: Leukapheresis, PROCEDURE: Positron Emission Tomography, DRUG: Stem Cell Mobilization Therapy
Anaplastic Large Cell Lymphoma, ALK-Negative, Follicular Helper T-Cell Lymphoma, Follicular Helper T-Cell Lymphoma, Angioimmunoblastic-Type, Peripheral T-Cell Lymphoma, Not Otherwise Specified
DCIS: RECAST Trial Ductal Carcinoma In Situ: Re-Evaluating Conditions for Active Surveillance Suitability as Treatment
Kim Nelson, RN - k.nelson@qlhc.org
NCT06075953
Inclusion Criteria:
A. Female, at least 18 years old
B. Previous diagnosis of HR+ DCIS (at least 50% ER or PR; biopsy will have been performed previously at diagnosis) with or without microinvasion
* Patients with a diagnosis of hormone positive DCIS who have undergone surgery with positive margins that have not been re-excised are candidates to enroll in the trial.
C. Patients who have previously received endocrine therapy should have a washout period of at minimum 4-6 weeks prior to the screening MRI on the RECAST-DCIS trial
D. Bilateral mammogram performed within up to 6 months (180 days) of the start of trial treatment may be used for screening evaluation. If a bilateral mammogram has been performed within 1 year (12 months) of the start of trial treatment, then a diagnostic unilateral mammogram within 6 months (180 days) of the start of trial treatment will be acceptable for screening evaluation.
E. MRI performed on an I SPY (RECAST) approved scanner within 2 months (60 days) of the start of trial treatment for lesion evaluation may be used for screening evaluation.
F. CBC w/ diff, CMP, and Lipid Panel within normal limits within a year of the start of trial treatment. Abnormal labs to be repeated within 60 days prior to the start of trial treatment. Patients will be considered eligible for screening labs that are abnormal or out-of-range if the investigator has deemed the lab results not-clinically significant
G. Negative urine or serum pregnancy test within 1 month of the start of trial treatment
H. Controlled HIV positive patients are allowed as long as their current medication does not contraindicate the study's investigational agent
I. Willingness and ability to provide tumor samples for research
Exclusion Criteria:
A. Pregnant or actively breastfeeding women
B. History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent based on review of the medical record and patient history
C. Invasive carcinoma or identification of a mass on MRI that is subsequently biopsied and found to be invasive cancer
D. Co-enrollment in clinical trials of pharmacologic agents requiring an IND
E. Ongoing treatment for DCIS other than what is specified in this protocol
F. Uncontrolled intercurrent illness, including psychiatric conditions, that would limit compliance with study requirements
G. Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of investigational agent and/or tamoxifen. Active inflammatory bowel disease or chronic diarrhea, known active hepatitis A/B/C\*, hepatic cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection or banding procedures
\*Active hepatitis, defined as: A (positive HA antigen or positive IgM); B (either positive HBs antigen or positive hepatitis B viral DNA test above the lower limit of detection of the assay); C (positive hepatitis C antibody result, and quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay)
H. Participants who are unable to swallow normally or unable to take tablets and capsules. Predictable poor compliance with oral treatment DRUG: Tamoxifen, DRUG: Exemestane, DRUG: Letrozole, DRUG: Anastrazole, DRUG: Testosterone + Anastrazole, DRUG: Elacestrant, DRUG: Z-endoxifen
Ductal Carcinoma in Situ
active surveillance, hormone therapy, endocrine therapy