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Testing the Use of Chemotherapy After Surgery for High-Risk Pancreatic Neuroendocrine Tumors
ctrrecruit@vcu.edu
NCT05040360
Inclusion Criteria:
* Participants must have a histologic diagnosis of well-differentiated pancreatic neuroendocrine tumor (pNET) that was resected between 14 and 120 days prior to registration. Participants must have a scan within 90 days prior to registration without evidence of metastatic disease. Acceptable scans are multiphase computed tomography (CT) abdomen, magnetic resonance imaging (MRI) with intravenous (IV) contrast of the abdomen, or positron emission tomography (PET)-CT DOTATATE imaging if the DOTATATE PET-CT included IV iodine contrast for the CT portion of the exam
* Resection must have been an R0 or R1 per treating investigator's assessment and/or pathology report
* Ki-67 testing, which is considered part of standard of care in the pathology report, must have been performed between 14 and 90 days prior to registration and the result must be \>= 3% and =\< 55%. Treating investigators are encouraged to contact the S2104 Study Chairs and/or the study pathology chair with questions. If more than one Ki-67 is reported (e.g., primary tumor versus lymph node or metastatic site), the highest one should be considered for the study eligibility criteria
* Participants with localized resected pNETS must have a Zaidi score of \>= 3 derived by the following factors and points:
* 1 point; symptomatic tumor defined as one of the following:
* Gastrointestinal bleed
* Jaundice
* Gastrointestinal obstruction
* Pain from primary tumor prior to surgical resection
* Pancreatitis
* 2 points; primary pancreas tumor size \> 2 cm
* 1 point; Ki-67 3% to 20%
* 1 point; lymph node positivity = 1
* 6 points; Ki-67 21% to 55%
* Participants may have received resection/ablation of liver oligo-metastatic disease (up to 5 liver metastases) at the time of well-differentiated pNET resection
* Participants must have recovered from effects of surgery as determined by the treating investigator
* Participants must be \>= 18 years old
* Participants must have Zubrod performance status of 0-2
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Leukocytes \>= 3 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count \>= 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelets \>= 100 x 10\^3/uL (within 28 days prior to registration)
* 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 registration)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 28 days prior to registration)
* Serum creatinine =\< 1.5 x institutional ULN (within 28 days prior to registration)
* Calculated creatinine clearance \>= 50 ml/min (within 28 days prior to registration)
* Participants must be able to swallow pills
* Participants must be able to tolerate CT or magnetic resonance (MR) imaging including contrast agents as required for their treatment and the protocol
* No other active malignancy or history of prior malignancy is allowed, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
* 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
Exclusion Criteria:
* Participants must not have unresected or unablated metastatic disease
* Participants must not have clinically apparent central nervous system metastases or carcinomatous meningitis
* Participants must not have received prior neoadjuvant therapy for treatment of pancreatic neuroendocrine tumor. Use of somatostatin analogs prior to surgery is permitted
* Participants must not have received somatostatin analogs after surgery
* Participants must not be planning to receive warfarin while on protocol treatment. Other anticoagulants are allowed
* Participants must not have history of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or capecitabine
* Participants must not have known absorption issues that would limit the ability to absorb study agents
* Participants must not have had an arterial thromboembolic event, unstable angina, or myocardial infarction within 12 months prior to registration
* Participants must not have active or uncontrolled infection
* Participants must not have serious medical or psychiatric illness that could affect study participation in the judgement of the treating investigator
* Participants must not be pregnant due to the possibility of harm to the fetus. 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 DRUG: Capecitabine, DRUG: Temozolomide
Metastatic Malignant Neoplasm in the Liver, Pancreatic Neuroendocrine Tumor, Stage I Pancreatic Neuroendocrine Tumor AJCC v8, Stage II Pancreatic Neuroendocrine Tumor AJCC v8, Stage III Pancreatic Neuroendocrine Tumor AJCC v8
Evaluate the Safety, Tolerability, Pharmacodynamics and Efficacy of CNP-106 in Subjects With Myasthenia Gravis
Joseph Mide - jmide@courpharma.com
NCT06106672
Inclusion Criteria:
• Subjects who are willing and able to provide Institutional Review Board (IRB) approved written informed consent and privacy language as per national regulations.
• Men and non-pregnant women, ages 18-75 years inclusive.
• Female subjects of childbearing potential must agree not to become pregnant during the clinical study, have a negative pregnancy test at the Screening Visit, and agree to one of the following: * Use two highly effective forms of birth control starting at initial screening and continuing throughout the study duration. * Practice abstinence starting at initial screening and continuing throughout the study duration.
• Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class III-IV (Cohort 1). Upon successful DMC review and approval of preliminary safety data obtained from Cohort 1 through Day 15, Cohort 2 will enroll subjects with MGFA Clinical Classification Class II-IV.
• Subjects positive for anti-AChR antibodies by radioimmunoassay (RIA) (Mayo Clinic). 6, Subjects with MG-ADL Score ≥ 6 at Screening and Baseline Visit with ≥ 50% of the score derived from non-ocular symptoms.
• Subjects with QMG Score ≥ 11 at Screening and Baseline Visit. 8. For subjects on any medication used to treat the symptoms of MG (ex. Corticosteroids, pyridostigmine), subjects must be on a stable dose for a minimum of 90 days prior to enrollment and must agree not to increase their dose through clinical study duration unless reviewed and approved by the medical monitor and the site investigator.
• Female subjects who agree to not breastfeed starting at initial screening and throughout the study duration.
• Female subjects who agree to not donate ova starting at initial screening and throughout the study duration.
• Male subjects with a spouse or partner of childbearing potential, who themselves and their spouse or partner agree to practice an effective form of birth control as discussed with the study doctor or study staff starting at Screening and throughout the study duration.
Exclusion Criteria:
• Subjects with a Myasthenia Gravis Foundation of America Clinical Classification Class I or V.
• Subjects with a history of cerebrovascular accident in the past 12 months.
• Subjects with MG-ADL Score \< 6 at Screen or Subjects with MG-ADL Score ≥ 6 at Screen with ˂ 50% of the score derived from non-ocular symptoms.
• Subjects with QMG Score \< 11 at Screen.
• Subjects who have used the following medications: * Tacrolimus within 6 months prior to the first dosing; * Methotrexate within 5 half-lives or 90 days after last dose (whichever is longer); * Anti-FcRn inhibitors (ex. Efgartigimod) within 5 half-lives or 90 days after last dose (whichever is longer); * C5 complement inhibitor (ex. Eculizumab) within 5 half-lives or 90 days after last dose (whichever is longer); * Anti-CD20 (ex. Rituximab) within 5 half-lives for 90 days after last dose (whichever is longer); * Inclusion of subjects on other immunomodulatory drugs will be at the discretion of the medical monitor and study site investigator.
• Subjects who have used immunoglobulins given SC or IV (SCIg or IVIg) or plasmapheresis/plasma exchange (PE) within 4 weeks before Screening.
• Subjects who have had thymectomy or any other thymic surgery performed within 12 months prior to Screening.
• Subjects with untreated thymic malignancy, carcinoma, or thymoma.
• Subjects with a history of tuberculosis or positive PPD skin test.
• Subjects who have received administration of any live vaccine (other than intranasal Influenza) within 28 days or subunit vaccine within 14 days prior to Screening or are planning to receive any vaccination throughout the study duration.
• Subjects who have received any COVID-19 vaccine within 14 days prior to Screening. Subjects who have received the first dose of any COVID-19 vaccine may not screen for the study until 14 days following their last dose of the vaccine if applicable.
• Subjects with laboratory test results at Screening or prior to study dosing that are outside the normal limits and considered by the investigator to be clinically significant. Note: Clinically significant laboratory test results at screening that are related to the condition (MG) are acceptable as long as all inclusion and no other exclusion criteria are met.
• Subjects with positive test results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antigen/antibody as determined at Screening.
• Subjects with a history of or currently active immune disorders other than MG (including autoimmune disease) unless the condition, after discussion with the medical monitor and study site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
• Subjects with a history of or current active diseases other than myasthenia gravis requiring immunosuppressive drugs (including azathioprine, prednisone, prednisolone, budesonide, cyclosporine, tacrolimus, methotrexate, or mycophenolate mofetil) unless the condition, after discussion with the medical monitor and site investigator, has been deemed to be acceptable for the subject's participation in this clinical study.
• Subjects with a clinical history of significant cardiovascular disease as determined by the Investigator.
• Subjects with a complication or medical history of malignancy within the past 5 years which, in the investigator's opinion, makes the subject unsuitable for study participation.
• Subjects with a history of mast cell activation disease.
• Subjects who, in the investigator's opinion, will be unable to adhere to study procedures.
• Subjects who have received an investigational therapy other than CNP-106 within 28 days or 5 half-lives, whichever is longer, prior to Screening.
• Subjects with any known active condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
• Known sensitivity to any components of CNP-106 (PLGA, sucrose, mannitol or sodium citrate).
DRUG: CNP-106, OTHER: Placebo
Myasthenia Gravis, Generalized Myasthenia, AChR Myasthenia Gravis, MuSK MG
Addition of Antibiotics to Upfront Treatment Regimen for Colorectal Cancer
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06728072
Inclusion Criteria:
* Diagnosis of stage IV colorectal cancer
* Measurable disease by Response evaluation criteria in solid tumors (RECIST) 1.1 criteria
* Planned first-line treatment with a 5FU-based doublet chemotherapy regimen for colon cancer, specifics of the regimen at the discretion of the treating physician Note: Patients who have received adjuvant therapy \>6 months prior are eligible
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
* Absolute neutrophil count (ANC) ≥1,500 cells/μL
* Platelet count ≥100,000 cells/μL
* Hemoglobin ≥8 g/dL Note: The use of transfusion or other intervention to achieve hemoglobin ≥8 g/dL is acceptable.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) Note: Patients with documented liver metastases: AST and ALT ≤5 × ULN
* Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥40 mL/min using the Cockcroft-Gault equation: (140 - age) × body weight/plasma creatinine × 72 (× 0.85 if female)
* Radiographically measurable disease by RECIST 1.1
* Nonpregnant and not actively breastfeeding
* Sexually active patients of childbearing potential and their partners must agree to use medically acceptable form of contraception, per treating investigator, throughout the study Patients should continue to use medically acceptable methods of contraception after study treatment ends, following the guidance for their specific chemotherapy regimen.
Childbearing potential excludes:
Age \> 50 years and naturally amenorrhoeic for \> 1 year OR previous hysterectomy or bilateral salpingo-oophorectomy
Exclusion Criteria:
* ongoing full dose anticoagulation Note: Patients on full dose anticoagulation may be approached to discuss study participation if lowering anticoagulation dose is feasible per the discretion of the treating investigator. Patients will be required to lower the anticoagulation dose by half 48 hours before beginning study drugs
* Total colectomy
* Diagnosed with Cockayne Syndrome
* Using disulfiram, tizanidine, or theophylline and unable to stop taking these medications for the length of the microbiome modulation therapy
* On methotrexate doses of 15 mg/week or more
* History of allergic reaction to ciprofloxacin, metronidazole, or aspirin
* Antibiotic use in the 30 days before chemotherapy start Note: Use of antibiotics intended for prophylaxis at the time of surgery is allowed
* Corrected QT interval (QTc) \>480 on baseline ECG
* Clinically significant hematuria, hematemesis, or hemoptysis of \>0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of microbiome modulation therapy (significance determined by treating investigator)
* Diagnosed with a malabsorptive syndrome
* Inability to swallow tablets DRUG: Standard of Care Chemotherapy + Metronidazole, ciprofloxacin, aspirin
Colorectal Cancer, CRC
Colorectal Cancer, CRC
A Single-session Intervention Adaptation of the Habit Framework for the Prevention of Eating Disorders
Courtney Breiner - breinerc@vcu.edu
NCT06861608
Inclusion Criteria:
* EAT-26 score ≥ 20 ( EAT-26, participants will meet the "referral criteria" which includes a score of 20 or more or meeting frequency criteria on bingeing, purging, laxative/diuretic use, and/or exercise.)
* English-language fluency, self-reported3
* Access to a phone, tablet, or computer
Exclusion Criteria:
* Failure to correctly complete one of the attention checks in the survey prior to the intervention
* Failure to correctly complete both anagram tasks in the survey prior to the intervention
* Completion of the screening survey or pre-intervention surveys in an improbably fast time BEHAVIORAL: Screening Questionnaire, BEHAVIORAL: Pre-Intervention Questionnaires (~10 minutes), BEHAVIORAL: SSI (Single-session intervention (~30 minutes) Active arm, BEHAVIORAL: SSI (Single-session intervention (~30 minutes) control arm, BEHAVIORAL: End-of-Intervention Questionnaires (~5 minutes)
Eating Disorder Not Otherwise Specified
prevention of eating disorders
A Study of the TactiFlex SE Catheter and Volt PFA Generator in Subjects With PAF: (FlexPulse IDE)
Todd Stirman - todd.stirman@abbott.com
NCT06676072
Inclusion Criteria:
• Documented symptomatic paroxysmal atrial fibrillation (PAF). Documentation requirements are as follows:
• Physician's note indicating recurrent self-terminating AF with ≥ 2 episodes of PAF within the 6 months prior to enrollment AND
• One electrocardiographically documented PAF episode within 12 months prior to enrollment. NOTE: Documented evidence of the AF episode must either be continuous AF on a 12-lead ECG or include at least 30 seconds of continuous AF from another ECG device.
• Plans to undergo a catheter ablation procedure due to symptomatic PAF and is refractory, intolerant, or contraindicated to at least one Class I-IV AAD medication
• At least 18 years of age
• Able and willing to comply with all trial requirements including pre- procedure, post-procedure, and follow-up testing and requirements
• Informed of the nature of the trial, agreed to its provisions, and has provided written informed consent as approved by the Institutional Review Board/Ethics Committee (IRB/EC) of the respective clinical trial site.
Exclusion Criteria:
• Previously diagnosed persistent or long-standing persistent atrial fibrillation (Continuous AF greater than 1 year in duration)
• Arrhythmia due to reversible causes including thyroid disorders, acute alcohol intoxication, electrolyte imbalance, severe untreated sleep apnea, and other major surgical procedures in the preceding 90 days
• Known presence of cardiac thrombus
• Left atrial diameter (LAD) \> or equal to 5.0 cm (anteroposterior diameter) within 180 days prior to the index procedure
• Left ventricular ejection fraction (LVEF) \< or equal to 35% as assessed with echocardiography or computerized tomography (CT) within 180 days prior to the index procedure
• New York Heart Association (NYHA) class III or IV heart failure
• Body mass index \> or equal to 40 kg/m2
• Pregnant or nursing
• Patients who have had a ventriculotomy or atriotomy within the preceding 28 days of procedure
• Myocardial infarction (MI), acute coronary syndrome, percutaneous coronary intervention (PCI), or valve or coronary bypass grafting surgery within preceding 90 days
• Stroke or TIA (transient ischemic attack) within the last 90 days
• Heart disease in which corrective surgery is anticipated within 180 days after procedure
• History of blood clotting or bleeding abnormalities including thrombocytosis, thrombocytopenia, bleeding diathesis, or suspected anti- coagulant state
• Contraindication to long-term anti-thromboembolic therapy
• Patient unable to receive heparin or an acceptable alternative to achieve adequate anticoagulation
• Known sensitivity to contrast media (if needed during the procedure) that cannot be controlled with pre-medication
• Previous left atrial surgical or left atrial catheter ablation procedure (including left atrial appendage (LAA) closure device)
• Plans to have an LAA closure device implanted during the follow-up period
• Presence of any condition that precludes appropriate vascular access
• Severe mitral regurgitation (regurgitant volume ≥ 60 mL/beat, regurgitant fraction ≥ 50%, and/or effective regurgitant orifice area ≥ 0.40cm2)
• Previous tricuspid or mitral valve replacement or repair
• Patients with prosthetic valves
• Patients with a myxoma
• Patients with an interatrial baffle or patch as the transseptal puncture could persist and produce an iatrogenic atrial shunt
• Stent, constriction, or stenosis in a pulmonary vein
• Rheumatic heart disease
• Hypertrophic cardiomyopathy
• Active systemic infection
• Renal failure requiring dialysis
• Severe pulmonary disease (e.g., restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces severe chronic symptoms
• Presence of an implantable therapeutic cardiac device including permanent pacemaker, biventricular pacemaker, or any type of implantable cardiac defibrillator (with or without biventricular pacing function) or planned implant of such a device for any time during the follow-up period. Presence of an implantable loop recorder is acceptable as long as it is removed prior to insertion of the investigational device.
• Patient is currently participating in another clinical trial or has participated in a clinical trial within 30 days prior to screening that may interfere with this clinical trial without pre-approval from this study Sponsor
• Unlikely to survive the protocol follow up period of 12 months
• Presence of other medical, anatomic, comorbid, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
• Individuals without legal authority
• Individuals unable to read or write
DEVICE: PFA Ablation catheter
Atrial Fibrillation (AF), Atrial Arrhythmia, Paroxysmal AF, Drug Refractory Paroxysmal Atrial Fibrillation
Symptomatic, recurrent, drug refractory PAF, Atrial Fibrillation, Paroxysmal AF, Pulsed Field Ablation, Radio Frequency, PFA
Oral Health In Cirrhosis of the Liver (ORACLE) (ORACLE)
Jasmohan Bajaj, MD - jasmohan.bajaj@vcuhealth.org
NCT06052150
Inclusion Criteria:
* Age\>18 years
* Cirrhosis confirmed (liver biopsy, signs of current or prior decompensation, varices in patients with chronic liver disease, nodular liver on imaging, AST\>ALT and platelet count \>150K in patients with chronic liver disease, ultrasound, or MR elastography suggestive of cirrhosis).
* Willing and able to give consent
Exclusion Criteria:
* Unclear diagnosis of cirrhosis
* Unable or unwilling to consent
* Edentulous
* Prior organ transplant
* On anticoagulant therapy PROCEDURE: Dental exam and periodontal cleaning if needed
Cirrhosis, Periodontal Diseases
Safety and Tolerability Study of GIM-531 in Advanced Solid Tumors
Jayadev Sureddi, CBCC CRO - jayadev.sureddi@cbcc.global
NCT06425926
Key
Inclusion Criteria:
* Written informed consent
* Cytologically or histologically confirmed locally advanced or metastatic solid tumor that has progressed on standard therapy or for which no standard therapy exist; or be intolerant of standard therapy
* Have not received an experimental drug within 4 weeks or 5 half-lives (whichever is shorter) of study drug treatment or already be enrolled in a clinical study
* ECOG performance status 0-1
* Laboratory and ECG assessments within 28 days of enrollment including acceptable cardiac, renal, and hepatic functions
* Agree to baseline core needle biopsy or archival (within 12 months of screening) tumor submission; Note: Participants whose only site(s) of disease are in areas considered moderate or high risk for biopsy complications may be enrolled without a fresh biopsy upon Sponsor approval.
* Non pregnant participants; female participants of child bearing potential with non-sterile partners agree to use an effective form of contraception from the time of first dose of study drug (or 14 days prior to first dose for oral contraception) until 7 months after the last dose of study drug. Effective forms of contraception include hormonal (injection or oral), double barrier method, or intrauterine device. Non-sterile male participants with sexual partners of childbearing potential agree to use a barrier contraception method and agree to not donate sperm from the time of first dose of study drug until 4 months after the last dose of study drug.
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Phase 1 Expansion Cohorts Specific Inclusion Criteria (in addition to above inclusion criteria):
* NSCLC: Participants must have locally advanced/unresectable or metastatic NSCLC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
* TNBC: Participants must have locally advanced unresectable, recurrent, or metastatic TNBC. Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
* Ovarian Cancer: Participants must have locally advanced unresectable, recurrent, or metastatic ovarian cancer. Participants must have platinum-resistant ovarian cancer defined as disease recurrence or within 6 months after the last administration of platinum-based chemotherapy. Participants must have received no more than 1 line of therapy after development of platinum resistance. Maintenance treatment with Poly(ADP-ribose) polymerase inhibitors (PARPi) or bevacizumab are not counted as separate lines of therapy.
* Tumors with AKT3 mutation/amplification: Participants must have a locally advanced unresectable, recurrent, or metastatic solid malignancy. Participants with known AKT3 mutation/amplification based on next generation sequencing (NGS) performed per local standard of care.
Phase 2 Specific Inclusion Criteria (in addition to above inclusion criteria):
* Have confirmed unresectable Stage III or metastatic Stage IV cutaneous melanoma, NSCLC, or RCC that has radiographically progressed (as confirmed by imaging assessed by the Investigator) on an approved single-agent or combination anti-PD-1 therapy
* Must have received the anti-PD-1 therapy containing regimen as the latest line of treatment and be eligible to restart or to continue anti-PD-1 therapy in combination with GIM-531
* BRAF wild-type melanoma or RCC: Participants must have received no more than 2 prior lines of therapy in the advanced/metastatic setting
* BRAF (V600) mutant melanoma or NSCLC: Participants must have received no more than 3 prior lines of therapy in the advanced/metastatic setting.
Key Exclusion Criteria:
* Ongoing \>Grade 1 toxicity from prior therapy according to Common Terminology Criteria for Adverse Events v5.0 (Note: Grade 2 alopecia and Grade 2 sensory neuropathy are not exclusionary)
* Has known leptomeningeal disease, spinal cord compression, or brain metastases, except participants with the following:
* Brain metastases that have been treated and are clinically stable for at least 4 weeks prior to the first administration of study drug; Note: Participants receiving steroids for brain metastases must be either off steroids or on a stable, or decreasing dose, of \<10 mg daily of prednisone (or equivalent) in order to be eligible for enrollment; and
* No ongoing neurological symptoms related to the anatomic location of the brain metastases.
Note: Neurological symptoms that are considered sequelae to treatment for brain metastases are allowed.
* Has known structural cardiac disease
* Has known serious arrythmia, serious dysrhythmia, history of long QT syndrome, or clinically relevant cardiac conduction abnormalities
* Has an active autoimmune disease that has required systemic treatment in the past 12 months (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* At time of screening, is receiving systemic steroid therapy (greater than or equal to 10 mg/day of prednisone or equivalent) or is taking any immunosuppressive therapy; Note: Use of topical, inhaled, nasal, or ophthalmic steroids is allowed.
* Has active and clinically significant bacterial, fungal, or viral infection, including known hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
* Has a history of, or currently has, an acquired or primary (congenital) immunodeficiency;
* Has had prior anti-cancer treatment with chemotherapeutic agents or immune modulating agents within \<4 weeks or 5 half-lives, whichever is shorter, prior to the first dose of study drug.
* Has received a live vaccine within 30 days of first dose of study drug;
* Has had or has planned major surgery within 2 weeks of the first dose of study drug;
* Inability to swallow an oral dose of a medication (eg, oral capsules)
* Is taking medications that are considered strong inducers or inhibitors of CYP2C8 or CYP3A4/5, P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), or sensitive substrates of P-gp and BCRP (Appendix C) that cannot be discontinued at least 1 week prior to first dose of study drug and for the duration of the study.
* Is taking drugs that modify gastric pH, such as proton-pump inhibitors (PPIs) or H2 blockers. Antacids such as calcium carbonate or aluminum hydroxide-based products are permitted. DRUG: GIM-531, DRUG: Anti-PD-1 monoclonal antibody
Melanoma Stage IV, Solid Tumor
PD-1 resistance, PD-1 resistant/refractory, AKT3
Left vs Left Randomized Clinical Trial
Mihail G Chelu, MD, PhD - leftvsleft@bcm.edu
NCT05650658
Inclusion Criteria:
* Men and women 18 years of age or older.
* A LVEF ≤ 50% within 6 months prior to enrollment.
* Resting QRS duration ≥130 ms as evidenced by a historical 12-lead ECG prior to enrollment OR anticipated right ventricular pacing \>40% OR device in place with right ventricular pacing \> 40%.
* Are optimized on HF guideline directed medical therapy according to current HF published guidelines OR patient's physician will make an effort to start all guideline-directed medical therapy and titrate doses up as permitted by the participant clinical status and co-morbidities prior to implantation procedure.
Exclusion Criteria:
* Women who are pregnant, lactating, or plan to become pregnant during the course of the trial.
* Participants with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary, intervention in the next three (3) months.
* Enzyme-positive myocardial infarction within the past three (3) months prior to enrollment.
* Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past three (3) months prior to enrollment.
* Reversible non-ischemic cardiomyopathy (e.g., acute viral myocarditis).
* Participants with Chagas disease, cardiac sarcoidosis or amyloidosis.
* Expected to receive left ventricular assist device or heart transplantation within 6 months.
* Participants with primary severe valvular disease (e.g., aortic stenosis).
* Have a life expectancy of less than 12 months.
* Participants with irreversible brain damage from preexisting cerebral disease.
* Participants with a contrast dye allergy unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine.
* Participants participating in any other interventional cardiovascular clinical trial.
* Participants who would be unable to comply with the study's follow-up visit schedule; or
* Participants who had any prior unsuccessful attempt at implantation of biventricular pacing (BiVP), His Bundle Pacing (HBP), or Left Bundle Branch Pacing (LBBP) device. DEVICE: His/LBBP, DEVICE: BiVP
Heart Failure, Heart Failure With Reduced Ejection Fraction, AV Block, LBBB, RBBB, Intraventricular Conduction Delay, Pacing-Induced Cardiomyopathy
CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy for Relapsed/Refractory B Cell Non-Hodgkin Lymphoma (ANTLER)
Socorro Portella, MD - clinicaltrials@cariboubio.com
NCT04637763
Inclusion Criteria:
* Age greater than or equal to 18 at the time of enrollment
* Documented diagnosis of relapsed or refractory non-Hodgkin lymphoma after prior standard of care
* Eastern Cooperative Oncology Group performance status 0 or 1
* Adequate hematologic, renal, liver, cardiac and pulmonary organ function
Exclusion Criteria:
* Prior therapy with an anti-CD19 targeting agent
* Active or chronic graft versus host disease requiring therapy
* Prior allogeneic stem cell transplantation
* Central nervous system (CNS) lymphoma, prior CNS malignancy
* Prior seizure disorder, cerebrovascular ischemia, dementia, cerebellar disease or autoimmune disease with CNS involvement.
* Primary immunodeficiency
* Current or expected need for systemic corticosteroid therapy
* Current thyroid disorder. Hypothyroidism controlled with stable hormone replacement is permitted
* Other malignancy within 2 years of study entry, except curatively treated malignancies or malignancies with low risk of recurrence
* Unwillingness to follow extended safety monitoring GENETIC: CB-010, DRUG: Cyclophosphamide, DRUG: Fludarabine
Lymphoma, Non-Hodgkin, Relapsed Non Hodgkin Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Non Hodgkin Lymphoma, Lymphoma, B Cell Lymphoma, B Cell Non-Hodgkin's Lymphoma
Patient-reported Outcomes of Donor Site Healing Using Different Palatal Protection Techniques
Rafael Amorim Cavalcanti de Siqueira - amorimcavalr@vcu.edu
NCT06892496
Inclusion Criteria:
* At least 18 years of age
* Healthy or Mild controlled systemic diseases with no functional limitations (ASA I or ASA II)
* Sites with 1 to 3 teeth or implants requiring soft-tissue grafting
* Minimum palatal thickness of 2 mm
* Willing to participate and sign an informed consent
Exclusion Criteria:
* Patients with systemic conditions that could impair wound healing (i.e. diabetes, immunosuppressive, chemotherapy, etc.)
* Pregnant patients
* Patients with bleeding disorders or taking anticoagulants
* Smokers
* Patients with a history of palatal graft harvesting OTHER: Visual Analog scale (VAS) questionnaire, OTHER: Vacuum-formed retainer (VFR) technique, OTHER: 3-D printed acrylic resin stent (3DS) technique, OTHER: Flowable resin composite stent (FRC) technique, OTHER: Photographs of the patient's palate, OTHER: Measuring graft dimensions
Mucosal Erosion, Gingival Recession
soft tissue graft, pain, wound healing
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
BMS Study Connect Contact Center www.BMSStudyConnect.com - Clinical.Trials@bms.com
NCT04094610
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
ctrrecruit@vcu.edu
NCT02523014
* Documentation of disease:
* Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review
* Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3, or CCNE1 copy number gain in tumor sample as documented specifically by the central laboratory, regardless of whether prior genotype testing outside of the central laboratory was performed
* Progressive OR residual disease, as defined by the following:
* Residual measurable disease: residual measurable disease immediately after surgery without requirement for progression; for grade I disease, progression pre-operatively needs to be documented, with an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months; for patients with SMO/PTCH1 mutations enrolling to receive vismodegib, the change can occur between scans separated by up to 25 months; residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10 mm in both dimensions
* Progressive measurable disease: progression defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area); the change must occur between scans separated by no more than 25 months
* Post radiation patients: patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease after completion of radiation; if the progressive meningioma lesion has been radiated, at least 24 weeks must have elapsed from completion of radiation to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Measurable disease: measurable disease is defined by a bidimensionally measurable main lesion on MRI or computed tomography (CT) images (MRI preferred) with clearly defined margins and a minimum diameter of 10 mm in both dimensions; multifocal disease is allowed
* Prior treatment
* Prior medical therapy is allowed but not required
* No limit on number of prior therapies
* No chemotherapy, or other investigational agents within 28 days prior to registration
* No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study; additionally, no cases of nitrosourea or mitomycin C within 6 weeks prior to registration
* For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval \> 4 weeks must have elapsed from completion of radiation therapy to registration; if the progressive lesion is outside of the radiation field, then an interval of at least 2 weeks must have elapsed from completion of radiation to registration
* Steroid dosing stable for at least 4 days
* Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue
* No craniotomy 28 days prior to and after registration
* Not pregnant and not nursing:
\* A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* For patients with NF2/CDKN2A/AKT1/PIK3CA/PTEN mutation, CKDN2A copy number loss, or CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1 copy number gain: Age \>= 18 years
* For patients with SMO/PTCH1 mutation: Age \>= 30 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Patient history:
* Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months
* No metastatic meningiomas (as defined by extracranial meningiomas outside of CNS) allowed; spinal meningiomas are allowed
* No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug
* No known active hepatitis B or C
* No current Child Pugh class B or C liver disease
* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)
* No uncontrolled hypertension defined as blood pressure (BP) \> 140/90
* No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration
* No major surgery within 28 days prior to registration for any patients with AKT1/PIK3CA/PTEN mutations receiving capivasertib
* For patients going on to receive capivasertib (i.e. enrolled after Update #08)
* Patients should not have any of the following cardiac criteria:
* Any clinically important abnormalities in rhythm, conduction, or morphology of resting electrocardiogram (EKG) (e.g., complete left bundle branch block, third degree heart block)
* Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for Torsade de Pointes, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
* Experience any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure New York Heart Association (NYHA) class \>= II
* Uncontrolled hypertension (systolic blood pressure \[SBP\] \< 90 mmHg and/or diastolic blood pressure \[DBP\] \< 50 mmHg)
* Cardiac ejection fraction outside institutional range of normal or \< 50% (whichever is higher) as measured by echocardiogram (or multigated acquisition \[MUGA\] scan if an echocardiogram can't be performed or is inconclusive); left ventricular ejection fraction (LVEF) below lower limit of normal for site
* Patients should not have any of the following criteria:
* With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of registration
* Hemoglobin \< 9 g/dL (\< 5.59 mmol/L); note: any blood transfusion must be \>= 14 days prior to the determination of a hemoglobin \>= 9 g/dL (\>= 5.59 mmol/L)
* Proteinuria 3+ on dipstick analysis or \> 500 mg/24 hours
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of capivasertib
* History of hypersensitivity to active or inactive excipients of capivasertib or drugs with a similar chemical structure or class to capivasertib
* Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
* Previous allogeneic bone marrow transplant
* Known immunodeficiency syndrome
* Concomitant medications (only regarding NF2/CDKN2A/CDK4/CDK6/CCND1/CCND2/CCND3/CCNE1/AKT1/PIK3CA/PTEN genetic alterations):
* Chronic concomitant treatment with strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors must discontinue the drug for 14 days prior to registration on the study for patients with NF2 mutation enrolled to GSK2256098, as well as for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib
* For NF2 patients going on to receive GSK2256098 and for patients with AKT1/PIK3CA/PTEN mutations enrolled to capivasertib: concomitant treatment with strong CYP3A4 inducers or CYP2D6 substrates is not allowed; patients must discontinue the drug 14 days prior to registration
* For NF2 patients going on to receive abemaciclib: avoid concomitant use of CYP3A inducers and strong CYP3A inhibitors; use caution with coadministered moderate or weak CYP3A inhibitors
* Diabetic status:
* For patients with NF2 or SMO/PTCH1 mutations: No uncontrolled diabetes defined as a known diabetic with HBA1C \> 7.5 OR fasting glucose \> 140 mg/dL.
* For patients with AKT1/PIK3CA/PTEN mutations:
* Glycosylated hemoglobin (HbA1C) \< 8.0% (63.9 mmol/mol)
* No type 1 diabetes mellitus
* No requirement for insulin for routine diabetic management and control
* No requirement for more than two oral hypoglycemic medications for routine diabetic management and control
* Patients with a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose \< 9.3 mmol/L (167mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Patients without a pre-existing diagnosis of type 2 diabetes mellitus must have fasting glucose =\< 7.0 mmol/L (126 mg/dL); fasting is defined as no caloric intake for at least 8 hours
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine OR =\< 1.5 mg/dl x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \> 50 mL/min
* Urine protein:creatinine ratio (UPC) =\< 45 mg/mmol
* Total bilirubin =\< 1.5 x upper limit of normal (ULN); except in case of Gilbert's disease
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x ULN
* Sodium, potassium, total calcium (corrected for serum albumin) \& phosphorus within normal limits per institutional guidelines
* QTcF \< 450 msec (QT calculated using Fridericia formula)
* Mean resting heart rate (determined from EKG) 50-100 beats per minute (BMP) (must be obtained from 12-lead EKG defined by a triplicate EKG for patients assigned to the capivasertib arm; patients assigned to all other arms will require a single EKG
* No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Hemoglobin \>= 8 g/dL
\* Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must not begin earlier than the day after the erythrocyte transfusion
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: Prior Treatment
* Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy prior to registration; a washout period of at least 28 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy)
* Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy; a washout period of at least 28 days is required between end of radiotherapy and registration
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]); screening is not required for enrollment in the absence of symptoms
* ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR ABEMACICLIB ARM: No personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
DRUG: Vismodegib, DRUG: FAK Inhibitor GSK2256098, DRUG: Capivasertib, DRUG: Abemaciclib
Intracranial Meningioma, Recurrent Meningioma, NF2 Gene Mutation
Research Participation With Transgender and Gender-Diverse Youth
An Pham, MD - an.pham@vcuhealth.org
NCT05927350
Inclusion Criteria:
* Gender identity different then sex assigned at birth
* Between the ages 15-21 years
Exclusion Criteria:
* Gender identity the same as their sex assigned at birth
* Younger than 15 years of age, and older than 21 years of age OTHER: Survey
Transgender Persons
Using Dichoptic Therapy to Treat Intermittent Exotropia
Evan Silverstein - evan.silverstein@vcuhealth.org
NCT06529016
Inclusion Criteria:
* Diagnosed with IXT
* one eye that is their preferred eye
* ages 4-7
* distance control scores of \<= 4
Exclusion Criteria:
* distance control scores of 5
* patients with visual acuity with vision that is worse in one eye by greater than two lines
* no preferred eye
* patients who would be unable to tolerate wearing the headset for 1 hour/day, 6 days/week, for 12 weeks. DEVICE: Luminopia, a virtual reality headset, OTHER: Paper pre- survey, OTHER: Paper Survey
Exotropia Intermittent
Dichoptic therapy
National Liver Cancer Screening Trial (TRACER)
Amit Singal, MD, MS - Amit.Singal@UTSouthwestern.edu
NCT06084234
Inclusion Criteria:
Patient must meet all of the following inclusion criteria:
• Adult patients ages 18-85 with cirrhosis from any etiology or with chronic hepatitis B with a PAGE-B score greater than 9 within 12 months of enrollment
• Patient is eligible for HCC surveillance according to treating physician or by the site investigator
• Able to provide informed consent
• Life expectancy \>6 months (after consent) as determined by the treating provider or site investigator
Exclusion Criteria:
Patient will be excluded for any of the following exclusion criteria:
• Child Pugh C cirrhosis
• History or clinical symptoms of hepatocellular carcinoma or cholangiocarcinoma
• History of solid nodule on baseline ultrasound (i.e., lesion 1cm or greater) within 9 months prior to consent without subsequent diagnostic CT/MRI demonstrating benign nature)
• AFP \>20 ng/mL within 6 months prior to consent, in the absence of a contrast-enhanced CT or MRI within 6 months of AFP (before or after) level demonstrating lack of suspicious liver lesions
• Newly diagnosed LR-3 greater than or equal to 1 cm within 6 months prior to consent
• History of LR-4, LR-5, or LR-M on multi-phase CT or contrast-enhanced MRI within 6 months prior to consent
• Presence of another active cancer besides non-melanomatous skin cancer or indolent cancer under active surveillance (e.g., prostate cancer or renal cell carcinoma) within the 2 years prior to consent
• Patient's provider is planning to use MRI- or CT- based surveillance moving forward
• History of a transjugular intrahepatic portosystemic shunt (TIPS)
• History of Fontan associated liver disease or cardiac cirrhosis
• History of solid organ transplantation
• Actively listed for liver transplantation
• Diagnosis of alcohol-associated hepatitis within 3 months prior to consent
• Documented current or continued signs and symptoms of acute Wilson disease (acute liver failure, acute neurological deficits, hemolysis)
• In patients with primary sclerosing cholangitis (PSC): Current active cholangitis within 90 days prior to consent
• Known or documented habitual non-adherence to previous research studies or medical procedures or unwillingness to adhere to protocol (e.g., unwilling to obtain consent or samples)
• In patients living with HIV: CD4+ T cell count less than 100 cells/mm3 within 60 days prior to consent
• Known pregnancy at consent
• Active warfarin use
DIAGNOSTIC_TEST: GALAD, DIAGNOSTIC_TEST: Liver Ultrasound with or without AFP
Carcinoma, Hepatocellular, Liver Cancer, Liver Cirrhosis, Hepatitis B
Hepatocellular carcinoma surveillance, GALAD, Alpha Fetoprotein
TAK-243 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes With Increased Blasts
ctrrecruit@vcu.edu
NCT03816319
Inclusion Criteria:
* Diagnosis of AML or MDS with increased blasts (MDS-IB) assessed by local laboratory review according to the 2022 World Health Organization (WHO) criteria for myeloid neoplasms. Both patients with MDS-IB1 (5-9% bone marrow blasts) and MDS-IB2 (10-19% bone marrow blasts) are eligible.
* Patients must have relapsed or refractory disease after receiving at least one prior line of therapy
* AML-specific inclusion criteria: Patients with relapsed or refractory AML with \>= 5% bone marrow blasts after receiving at least two courses of intensive induction chemotherapy (including, but not limited to, 7+3 regimen, fludarabine, cytarabine, idarubicin and filgrastim \[FLAG-Ida\] and mitoxantrone, etoposide, and cytarabine \[MEC\]) or 2 cycles of venetoclax-based lower intensity regimen (azacitidine plus venetoclax or low-dose cytarabine plus venetoclax), and without any other approved therapies available that would be more appropriate in the investigator's judgment. Patients who have received only one course of intensive induction chemotherapy but are not eligible for a second course because of decreased performance status or clear disease progression may be eligible for participation after discussion with the study principal investigator (PI). Patients with concomitant extramedullary disease relapse are eligible to participate, but not patients with isolated extramedullary relapse without bone marrow disease.
* MDS-specific inclusion criteria: Patients with relapsed or refractory MDS-IB with \>= 5% bone marrow blasts after at least 4 cycles of hypomethylating agent (HMA)-based therapy or at least two courses of intensive induction chemotherapy and meet criteria for stable disease (SD), progressive disease (PD) or disease relapse according to the International Working Group 2023 response criteria for higher-risk MDS. Patients must not have access to any other approved therapies that would be more appropriate in the investigator's judgment. Patients who have received less than 4 cycles of HMA-based therapy may be eligible to participate after discussion with the study PI if there is clear evidence of progression or intolerance to HMA-based therapy that precludes its continuation.
* Patients must have recovered from the effects of any prior systemic therapy, radiotherapy or surgery:
* Patients should not have received other investigational therapy within 2 weeks.
* Patients should not have received standard chemotherapy within 1 week of administration of study drug; hydroxyurea administration (for leukocyte count control) is permitted.
* Age \>=18 years. Because no dosing or adverse event data are currently available on the use of TAK-243 in patients \<18 years of age, children are excluded from this study.
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%).
* Serum bilirubin =\< 1.5 × institutional upper limit of normal (ULN).
* Patients with a known history of Gilbert's syndrome may enroll.
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 × institutional ULN.
* Serum creatinine \< 176 mcmol/L (2 mg/dL) OR
* Creatinine clearance \> 60 mL/min based on the Cockcroft-Gault equation.
* Documented normal cardiac function (\>= 50%) by echocardiogram or multi-gated acquisition (MUGA) scan.
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load withing 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, 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.
* The effects of TAK-243 on the developing human fetus are unknown and ubiquitin-activating enzyme inhibitors are known to be teratogenic. For this reason, female patients must be:
* Postmenopausal (age-related amenorrhea \>= 12 consecutive months or follicle-stimulating hormone \> 40 mIU/mL), for at least 1 year before the screening visit, OR
* Surgically sterile (i.e., who had undergone hysterectomy or bilateral oophorectomy), OR
If they are of childbearing potential:
* Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
* Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), OR
* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
* 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.
* Patients should have a minimum life expectancy of 1 month.
Exclusion Criteria:
* Patients with acute promyelocytic leukemia (APL) or AML with t(15;17)(q22;q12) - PML::RARA).
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), except anemia, neutropenia or thrombocytopenia of any grade and grade 2 peripheral neuropathy.
* Presence of any other malignancy requiring active therapy.
* Patients who are receiving any other investigational agents.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAK-243.
* Concomitant treatment with organic anion transport protein (OATP) and BCRP inhibitors or strong inducers/inhibitors of cytochrome P450 (CYP)3A4/5. Treatment with these agents must be discontinued at least 14 days prior to TAK-243 dosing. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product.
* Presence of an active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
* Presence of active graft-versus-host disease (GVHD) or continued treatment with systemic immunosuppressive agents following allogeneic hematopoietic stem cell transplantation (HSCT).
* Presence of any co-morbid condition that, in the opinion of the investigator, might compromise the patient's safety, might interfere with participation in the trial or might interfere with the interpretation of trial results.
* Pregnant and lactating/breast-feeding women are excluded from this study because TAK-243 is a UAE-inhibiting agent with the potential for teratogenic or abortifacient effects and there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TAK-243. Females of child-bearing potential must have a negative serum pregnancy test within 7 days before enrollment and should not be lactating/breast-feeding. Breastfeeding should be discontinued if the mother is treated with TAK-243.
* Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period.
* Patients with uncontrolled coagulopathy or bleeding disorder.
* Patients with known hepatic cirrhosis.
* Patients with known active cardiopulmonary disease defined as:
* Unstable angina withing 3 months prior to first dose of TAK-243;
* Myocardial infarction (MI) within 6 months prior to first dose of TAK-243 (patients who had MI and/or coronary revascularization more than 6 months before screening and who are without cardiac symptoms may enroll);
* Congestive heart failure (New York Heart Association \[NYHA\] Class III or IV;
* Cardiomyopathy with left ventricular ejection fraction (LVEF) \< 50%;
* Symptomatic pulmonary hypertension.
* Presence of active central nervous system (CNS) involvement (patients with prior CNS leukemia who have negative CNS cytology and who receive periodic prophylactic intrathecal chemotherapy are eligible).
* Patients with clinically significant arrhythmia:
* History of ventricular fibrillation or torsade de pointes at any time,
* Episode of grade \>= 3 atrial fibrillation or flutter in the last 3 months, defined as symptomatic episode, requiring urgent intervention (cardioversion, pacemaker or ablation) or with life-threatening consequences.
* Uncontrolled high blood pressure (i.e., systolic blood pressure \>180 mm Hg, diastolic blood pressure \> 95 mm Hg).
* Prolonged rate corrected QT (QTc) interval \>= 480 msec, calculated using the Fridericia method.
* Patients with known severe or very severe chronic obstructive pulmonary disease (defined as forced expiratory volume in one second (FEV1) less than 30% or less than 50% of predicted), interstitial lung disease, or pulmonary fibrosis.
* Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
* Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
* Patients with history of neutrophilic dermatosis (e.g. Sweet syndrome, pyoderma gangrenosum), relapsing polychondritis, polyarteritis nodosa and/or giant cell arteritis.
* Patients with VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) or any other autoinflammatory disease. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Echocardiography Test, PROCEDURE: Multigated Acquisition Scan, DRUG: UAE Inhibitor TAK-243
Myelodysplastic Syndrome With Excess Blasts, Recurrent Acute Myeloid Leukemia, Recurrent Myelodysplastic Syndrome, Recurrent Myelodysplastic Syndrome/Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia, Refractory Myelodysplastic Syndrome, Refractory Myelodysplastic Syndrome/Acute Myeloid Leukemia
CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma (CaMMouflage)
Caribou Biosciences - clinicaltrials@cariboubio.com
NCT05722418
Inclusion Criteria:
• Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable disease (according to IMWG diagnostic criteria.)
• Received at least 3 prior MM treatment lines of therapy which must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody as part of a prior line of therapy, either in monotherapy or in combination.
• Eastern Cooperative Oncology Group performance status grade of 0 or 1.
• Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.
Exclusion Criteria:
• Prior treatment with CAR-T cell therapy directed at any target.
• Autologous stem cell transplant within the last 6 weeks before lymphodepletion.
• Allogeneic stem cell transplant within 6 months before lymphodepletion.
• Known active or prior history of CNS involvement.
• Stroke or seizure within 6 months of signing ICF.
• Seropositive for or history of human immunodeficiency virus.
• Vaccinated with live, attenuated vaccine within 4 weeks prior to lymphodepletion.
• Hepatitis B infection.
• Hepatitis C infection.
• Known life-threatening allergies, hypersensitivity, or intolerance to CB-011 or its excipients.
BIOLOGICAL: CB-011
Relapsed/Refractory Multiple Myeloma
CaMMouflage, Allogeneic, Multiple Myeloma, Relapse Refractory Multiple Myeloma, CAR-T Cells, BCMA, Cell Therapy, Cellular Immuno-therapy, CB11A, CB-011, CB-011A, CAR-T, Anti BCMA, ALLO CAR T
Safety and Effectiveness of Valbenazine as Adjunct Therapy to Botulinum Toxin Injections in Cervical Dystonia
Ananna Zaman - Ananna.Zaman@vcuhealth.org
NCT06771323
Inclusion Criteria:
* Idiopathic CD (neck musculature first and most prominently affected)
* 18-75 years old (participants excluded if their dystonia symptoms began before age 18 as childhood-onset dystonia typically represents a genetic and/or primary generalized form of dystonia)
* Onset of dystonia ≥18 years old, no known hyperkinetic movement disorder-related genetic mutation
* Dystonia severity more than minimal and not very severe as defined by Toronto Western Spasmodic Torticollis Rating Scale-2 Motor Severity (TWSTRS-2-Severity) score ≥ 5 and ≤ 20.
* Stable on botulinum toxin injections last 90 days (BoNT dose change \<10% and patient reported stability of response over last two injection cycles)
* Stable on other neuroactive medications.
Exclusion Criteria:
* History of deep brain stimulation
* History of uncontrolled or untreated depression in the prior 3 months, suicidality, or history of suicide attempts
* History of uncontrolled liver disease or failure
* History of tardive dyskinesia or tardive dystonia
* Currently taking dopaminergic and/or anti-dopaminergic medications including VMAT2 inhibitors or other antipsychotic medications
* Exposure to dopaminergic and/or anti-dopaminergic medications including VMAT2 inhibitors or other antipsychotic medications in the last 30 days -Presence of parkinsonism or other movement disorder other than dystonia on exam -Receiving botulinum toxin injections at a planned frequency other than every 3 months or typically receive injections at intervals \<11 weeks or \>13 weeks -Known history of long QT syndrome or cardiac tachyarrhythmia or any clinically significant cardiac abnormality.
* Prolonged QTc as defined by \> 450 msec for men and \> 470 msec for women DRUG: Valbenazine, DRUG: Placebo
Cervical Dystonia
Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06731413
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous)
* Stage IV disease OR have recurrent disease and not be candidates for curative treatment such as combined chemo-radiation
* No previous line of treatment in the recurrent or metastatic setting. Neoadjuvant or adjuvant treatment more than 6 months before enrollment is acceptable.
* Age 70 or meeting frailty definition or above at the date of signing informed consent
* Absence of driver mutations that have first line Food and Drug Administration (FDA) approved targeted therapy
* PD-L1 tumor proportion score (TPS) of less than 50%
* Eastern Cooperative Oncology Group (ECOG) PS of 0-3
* Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment
* Absolute neutrophil count (ANC) ≥ 1,000/μL
* Platelets ≥ 75,000/μL
* Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion permitted)
* Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)
* Aspartate amino transferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT)serum glutamic-pyruvic transaminase (SGPT) ≤ 5.0 × institutional ULN
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* Participants with life expectancy of less than 3 months at the time of enrollment
* Has active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, or immunosuppressive drugs)
* Diagnosis of interstitial lung disease
* Creatinine clearance of \<30 mL/min
* Symptomatic, untreated central nervous system (CNS) disease or leptomeningeal disease. Patients with asymptomatic or treated CNS disease are eligible
* Required ongoing use of immunosuppressive medication, including steroids, with the following allowable exceptions:
* Doses less than or equal to the equivalent of prednisone 10 mg daily
* Short courses of steroids that are discontinued prior to enrollment
* Inhaled, intranasal and/or topical steroids
* Dexamethasone taper for treating vasogenic edema associated with CNS disease DRUG: Reduced Dose of Chemotherapy and Immunotherapy
Non-small Cell Lung Cancer, NSCLC, Advanced Non-small Cell Lung Cancer, Metastatic Non Small Cell Lung Cancer
Non-Small Cell Lung Cancer, NSCLC
HPV DNA-Guided Radiotherapy De-intensification of Head and Neck Squamous Cell Carcinoma (HN001)
Song W - UVARADONCClinicalTrials@uvahealth.org
NCT05962242
Inclusion Criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, ≥ 18 years of age
• Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx of any AJCC 8th edition stage.
• Eligible for and planning to receive definitive treatment or adjuvant treatment with radiotherapy.
• Participants who are receiving concurrent systemic anticancer therapy (e.g. chemotherapy or immunotherapy) for oropharyngeal cancer are eligible.
• For participants with T1-2 and N0 disease, chemotherapy is not required for eligibility. Participants may or may not receive chemotherapy per physician discretion.
• For participants with T3-4 and/or N+ disease, chemotherapy is required for eligibility.
• Participants may receive investigational agents with prior approval from the Principal Investigator.
• ECOG Performance Status of 0-2.
• p16 positive HPV as determined by NavDx and immunohistochemistry
• For females of reproductive potential: agreement to use adequate contraception during radiation treatment and for 6 months (or more if applicable based on other medications) after the end of radiation treatment.
Exclusion Criteria:
• Evidence of distant metastatic disease
• Prior history of radiotherapy to the head and/or neck
• Had surgery for oropharyngeal cancer within 8 months of enrollment unless it was an incomplete oncologic surgery. Participant is eligible if the gross tumor was not completely removed.
• Diagnosis of T3-4 and/or N+ disease with no plans to receive concurrent chemotherapy.
• Diagnosis of a current or prior invasive malignancy (except non-melanoma skin cancer) unless the participant has been disease free for at least 3 years.
• Participant is a prisoner
• Known contraindications to head and neck radiation therapy such as ataxia telangiectasia or scleroderma.
• Pregnancy or lactation
• Active or severe co-morbidities as defined by the following:
• Unstable angina and/or congestive heart failure requiring hospitalization up to 180 days before registration
• Transmural myocardial infarction up to 180 days before registration
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency as determined by the treating clinician resulting in clinical jaundice and/or coagulation effects or severe liver dysfunction.
• Acquired immune deficiency syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be slightly immunosuppressive. Protocol-specific requirements may also exclude immuno-compromised patients.
• Tobacco smoking history of 10 pack years or greater, or ≥ 20 pack years if smoking cessation occurred at least 1 year prior to enrollment
• Current use of antineoplastic drugs for other malignancies.
RADIATION: Radiation Therapy
Squamous Cell Carcinoma of the Oropharynx
Radiation Therapy, Radiotherapy, Head Cancer, Neck Cancer, Low Dose Radiation, HPV
mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma
Aishwarya Vijendran - aishwaryav@bsd.uchicago.edu
NCT05677490
Inclusion Criteria:
* Histologic documentation: HER2 negative adenocarcinoma as defined by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines (Bartley et al., Journal of Clinical Oncology \[JCO\] 2017) with known PD-L1 CPS (Any CPS is allowed, but should be known prior to registration)
* Stage: unresectable or metastatic
* Tumor site: esophagus, gastroesophageal junction, or stomach
* Measurable disease or non-measurable but evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No prior treatment for unresectable or metastatic disease
* Prior neoadjuvant or adjuvant cytotoxic chemotherapy or adjuvant immunotherapy is allowed as long as it was completed at least 1 year prior to registration
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance \>= 30 mL/min
* Total bilirubin =\< 1.5 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (in patients with liver metastasis: =\< 5 x ULN if clearly attributable to liver metastases)
* 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
* Patients positive for human immunodeficiency virus (HIV) are eligible only if they meet all of the following:
* On effective anti-retroviral therapy
* Undetectable HIV viral load by standard clinical assay =\< 6 months of registration
* 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 2B or better
* Patients who will receive nivolumab in addition to chemotherapy must not have any contraindications to immune checkpoint inhibitors
* Patients must not have active autoimmune disease that has required systemic treatment within 6 months prior to registration. Patients are permitted to receive immunotherapy if they have vitiligo, type I diabetes, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
* Patients must not have a condition requiring systemic treatment with either corticosteroids (\>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses (=\< 10mg/day prednisone equivalent) are permitted
* Patients must not have a history of noninfectious pneumonitis requiring steroids
* Patients with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents are ineligible
* This study includes the use of the mandatory patient completed measure, PRO-CTCAE. For this study the PRO-CTCAE is available in English, Spanish, Korean, Chinese (Simplified), and Russian, hence patients must be able to speak, understand and read in these languages. Ad-hoc translation of patient-reported measures is not permitted
Exclusion Criteria:
* Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
\* Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to registration is required
* No known Gilbert's syndrome or known homozygosity for UGAT1A1\*28 polymorphism
* No baseline grade \>= 2 peripheral neuropathy, neurosensory toxicity, or neuromotor toxicity per CTCAE version (v) 5.0 regardless of causality
* No medical condition such as uncontrolled infection or uncontrolled diabetes mellitus which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* No untreated, symptomatic brain metastasis. Patients with treated brain metastases are eligible if the following criteria are met: 1) follow-up brain imaging done at least in 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and 2) the patient no longer requires steroids, or is on a stable steroid dose for more than four weeks
* No allogeneic tissue/organ transplant DRUG: Fluorouracil, DRUG: Leucovorin Calcium, DRUG: Oxaliplatin, DRUG: Irinotecan, BIOLOGICAL: Nivolumab, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Advanced Esophageal Adenocarcinoma, Advanced Gastric Adenocarcinoma, Advanced Gastroesophageal Junction Adenocarcinoma, Clinical Stage III Esophageal Adenocarcinoma AJCC v8, Clinical Stage III Gastric Cancer AJCC v8, Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8, Clinical Stage IV Esophageal Adenocarcinoma AJCC v8, Clinical Stage IV Gastric Cancer AJCC v8, Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
Behavioral Exercise Training to Reduce Cardiovascular Disease Risk (EXTRA-PC)
Alexander R Lucas, PhD - Alexander.Lucas@vcuhealth.org
NCT06237179
Inclusion Criteria:
* Be diagnosed with stage II/III/IV prostate cancer
* Be currently undergoing treatment with ADT (intermittent or prolonged)
* Have completed local curative-intent treatment, including prostatectomy or definitive radiation;
* Be \>40 years of age up to 85;
* Be willing to sign an informed consent with HIPAA authorization form;
* Not have any hearing or sight impairments that result in the inability to use the telephone or hear normal conversation;
* Must be able to join an intervention group by personal computer, smartphone or telephone call and should agree to recording of an interview;
* Be without any serious medical condition that precludes safe participation in an exercise program;
* Speak English
Exclusion Criteria:
* Be unable to undergo MRI (i.e., ferromagnetic materials in body, inability to lie flat, claustrophobia);
* Have contraindications to exercise testing;
* Have pre-existing overt cardiovascular disease/heart failure;
* Active illness/infection;
* Hemoglobin \< 7.0 grams/dL
* Platelet count \< 10 x 109/L BEHAVIORAL: Exercise Training Intervention, BEHAVIORAL: Healthy Living Education
Prostate Cancer, Supportive Care
Prostate Cancer, Supportive Care, Exercise
Examining Lateralized Aspects of Motor Control Using Non-invasive Neural Stimulation
Brooke Dexheimer, PhD, OTD, OTR/L - dexheimerb@vcu.edu
NCT05947279
Inclusion Criteria:
* Right-handed as determined by the short-form Edinburgh Handedness Inventory
* Between the ages of 18 and 40
Exclusion Criteria:
* Mixed- or left-handed as determined by the short-form Edinburgh Handedness Inventory
* Self-reported history of any of the following:
Seizure and/or diagnosis of epilepsy Fainting spells Concussion with loss of consciousness Ringing in the ears (tinnitus) Cochlear implants Migraines Diagnosed psychological or neurological condition Metal in the scalp
* Any previous adverse reaction to a brain stimulation technique
* Any previous adverse reaction to 3D virtual reality environments (i.e. 'cybersickness')
* Possibility of being currently pregnant (for females only)
* Current open head wound or skin condition of the scalp
* Current implanted device(s) (i.e. cardiac pacemaker) BEHAVIORAL: Comparing motor adaptation reaching performance
Motor Adaptation and Generalization, Posterior Parietal Cortex, Cerebellum
Testing Continuous Versus Intermittent Treatment With the Study Drug Zanubrutinib for Older Patients With Previously Untreated Mantle Cell Lymphoma
Anne Beaven, MD - anne_beaven@med.unc.edu
NCT05976763
Inclusion Criteria:
* • Histologically confirmed mantle cell lymphoma with cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (FISH) as confirmed by the enrolling center
* Any stage allowed (stage I-IV)
* Presence of measurable disease, defined as \>= 1 nodal lesion that is \> 1.5 cm in longest diameter or \>= 1 extranodal lesion that is \> 1 cm in longest diameter
* Steroids for management of mantle cell lymphoma are allowed up to a dose of prednisone 100mg/day (or equivalent) for up to 7 days
* No prior systemic treatment for mantle cell lymphoma
* No prior radiation treatment for stage I MCL
* No prior exposure to a BTK inhibitor or anti-CD20 monoclonal antibody
* No prior stem cell transplant
* Age \>= 70 years OR age \>= 60 to \< 70 years with comorbidities precluding autologous stem cell transplantation (autoSCT) including at least one of the following: a) cardiac ejection fraction (EF) \< 45%, b) diffusing capacity for carbon monoxide \< 60% predicted; c) creatinine clearance \< 70 but \> 30ml/minute (min); d) Eastern Cooperative Oncology Group (ECOG) performance status of 2, which poses an unacceptable risk of toxicity for high-dose therapy and stem cell transplantation; or e) Cumulative Illness Rating Scales (CIRS) total score \> 6
* ECOG Performance Status 0-2
* Absolute neutrophil count (ANC) \>= 750/mm\^3 (without growth factor support within 7 days)
* Platelet count \>= 75,000/mm\^3 (or \>= 50,000/mm\^3 for patients with bone marrow involvement of lymphoma) without growth factor support or transfusion within 7 days
* Creatinine clearance \>= 30 mL/ min determined by either: a) Estimation using the Cockcroft-Gault equation or b) Measurement by nuclear medicine scan or 24 hour urine collection
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
* Aspartate transferase (AST) / alanine transaminase (ALT) =\< 3 x ULN
* Patients should not be considered candidates for stem cell transplant or must have declined a stem cell transplant strategy
* No clinically significant cardiovascular disease including the following
* Unstable angina within 3 months before registration
* New York Heart Association class III or IV congestive heart failure
* History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
* QT correction formula (QTcF) \> 480 msecs based on Fredericia's formula
* History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* No active Hepatitis B or Hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have an undetectable HCV viral load
* 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
* No history of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention
* No history of stroke or intracranial hemorrhage within 6 months prior to registration
* No disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction. Patient must be able to swallow pills
* Potential trial participants should have recovered from major surgery
* No vaccination with a live vaccine within 35 days prior to registration
* No hypersensitivity to zanubrutinib or rituximab or any of the other ingredients of the study drugs
* Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study.
* Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
* Avoid use of moderate CYP3A4 inhibitors, PGP inhibitors, and moderate CYP3A4 inducers
* Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional DRUG: Zanubrutinib, BIOLOGICAL: Rituximab, OTHER: Patient Observation, PROCEDURE: Bone Marrow Biopsy, OTHER: Fludeoxyglucose F-18, PROCEDURE: Positron Emission Tomography, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Esophagogastroduodenoscopy, PROCEDURE: Colonoscopy, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Mantle Cell Lymphoma
Health Education Approach to Lung Screening (HEALS)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06070870
Inclusion Criteria:
* Meets current USPSTF guidelines for lung cancer screening (LCS)
* 20 pack-year smoking history Note: A pack-year is a way of calculating how much a person has smoked in their lifetime.
One pack-year is the equivalent of smoking an average of 20 cigarettes-1 pack-per day for a year.
* Currently smokes or has quit smoking within the past 15 years
* Identifies as Black or African-American Note: Both Hispanic/Latino and Non-Hispanic/Latino patients are eligible as long as they also identify as Black or African-American (eg, Afro-Latino).
* Willing to complete all navigation-related study activities
* Able to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
A patient who meets any of the following exclusion criteria is ineligible to participate in the study:
* Known history of cancer (except squamous cell skin cancer), or coughing up blood in the past 5 years, as reported by the individual
* Has undergone a previous lung cancer screening
* Inability to speak English
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements BEHAVIORAL: Patient Navigation
Lung Cancer
Lung cancer, Screening
Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality (REMAIN1)
Massey IIT Research Operations - masseyepd@vcu.edu
NCT06370000
Inclusion Criteria:
* Patients must have histologically or cytologically confirmed non-Acute Promyelocytic (APL) FLT3 negative AML and have completed induction and consolidation as defined by the treating physician and must be in complete response (CR), Complete response with partial hematologic recovery (CRh), or Complete response with incomplete count recovery (CRi) at time of study enrollment
* For patients in CR1, AML disease phenotype must be one that is considered for allo HCT in CR1 (intermediate or high risk by European Leukemia Net (ELN), MRD+ CR, slow clearance of MRD) or any AML phenotype (aside from FLT3+ and APL) in CR2 and beyond
* Medically eligible for allogeneic hematopoietic cell transplant (allo HCT) as defined by either: treating physician discretion, transplant physician discretion, or hematopoietic cell transplantation-specific Comorbidity index (HCT-CI) index of 5 or less
* Age ≥ 18 years
* Enrollment must occur within 4 months of completion of therapy
* A patient or staff identified health disparity in 1 of the 5 Centers for Disease Control (CDC) defined social determinants of health (SDOH). This may include financial difficulties, lack of caregiver support, difficulties with medical literacy, rurality, appropriate access to health care, lack of an appropriate allogeneic hematopoietic cell transplant (allo HCT) donor, substance abuse
* Patient must have adequate organ function defined as: Creatinine clearance (by Cockroft-Gault formula) greater than or equal to 29 mL/min, total bilirubin and aspartate aminotransferase/ alanine transaminase (AST/ALT) ≤ to institutional 2x upper limit of normal (except Gilbert's syndrome, which may enroll if \< 2x patient's baseline total bilirubin)
* Eastern Cooperative Oncology Group (ECOG) 0,1,2,3
* Ability to take oral medications
* No history of malabsorption syndrome which, in the investigator's opinion, may inhibit absorption of oral medications
* Women of childbearing potential must consent to effective contraception during study treatment and at least 6 months following the last dose. Women who are breastfeeding are also excluded
* Male patients must consent to effective contraception during study and at least 3 months after last dose
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria A patient who meets any of the following exclusion criteria is ineligible to participate in the study.
* FMS-like tyrosine kinase 3 (FLT3 ITD) or tyrosine kinase domain (TKD) mutation
* Uncontrolled central nervous system (CNS) involvement
* History of hypersensitivity or allergic reaction to azacitidine or its components
* Stem cell transplant within previous 3 months prior to initiation of study therapy
* Uncontrolled intercurrent illness or infection
* History of prior therapy with oral azacitidine
* Female patients who are pregnant or intend to donate eggs during the study or for 6 months after receiving their last dose of study drug
* Male patients who intend to donate sperm during the course of this study or for 3 months after last dose
* Other malignancy for which the patient is currently receiving therapy (except excisable skin cancer)
* Medical, psychological, or social condition that, in the opinion of the investigator, may increase the participant's risk or limit the participant's adherence with study requirements DRUG: Oral Azacitidine
Acute Myeloid Leukemia
miroliverELAP® for the Treatment of Acute Liver Failure: A Phase 1 Trial
Joshua Carlson - jcarlson@miromatrix.com
NCT06285253
Inclusion Criteria:
• 18 years to 80 years old at the time of signing the informed consent
• Subject must:
• be deemed competent to consent by an independent qualified practitioner, or
• have consent given by a Legally Authorized Representative
• Subject should be in the intensive care unit
• Be diagnosed with 4.1. Acute Liver Failure defined as:
• INR ≥ 2.0, and
• Hepatic Encephalopathy Grade II-III (West Haven Criteria), and
• Less than 4 weeks (28 days) of disease duration 4.2. Severe Acute Alcohol-Associated Hepatitis as defined as:
• Hepatic Encephalopathy Grade I-III (West Haven Criteria), and
• Model for End-Stage Liver Disease (MELD) Score ≥ 20, and
• INR ≥ 2.0, and
• No overt evidence of cirrhosis 4.3. Acute on Chronic Liver Failure:
• Hepatic Encephalopathy Grade I-III (West Haven Criteria), and
• Model for End-Stage Liver Disease (MELD) Score ≥ 20, and
• INR ≥ 2.0, 5\. Subject is not a candidate for liver transplant and will not become a candidate in the event of worsening conditions. Exclusion Criteria
• Grade IV West Haven Encephalopathy Criteria
• Previous liver transplant
• Currently requires chronic hemodialysis (CRRT or other forms of continuous renal replacement are allowed).
• Uncontrolled documented infection, hypotension, or refractory shock. This is defined as a need for a single vasopressor, or combination of vasopressors, that exceed a norepinephrine equivalent of 0.5 mcg/kg/min.
• Liver injury due to trauma
• Any current liver cancer
• Currently on medications with a narrow therapeutic index
• Platelet count \< 40,000 μL
• If the subject is intubated and has an acute lung injury
• Experiencing a bleeding event, defined as:
• Active gastrointestinal or other overt bleeding event, or
• Hemoglobin drop \> 3g/dL within the past 24 hours, or
• Received ≥ 3 units of red blood cell transfusion within the past 24 hours
• Female that is currently pregnant, planning to be pregnant, or currently breastfeeding
• Refusal to receive blood products
COMBINATION_PRODUCT: miroliverELAP treatment
Acute Liver Failure, Acute Liver Injury, Drug Induced, Acute on Chronic Liver Failure (ACLF), Acute Alcoholic Hepatitis
Acute liver failure, Extracorporeal liver assist, Bioengineered liver
Targeted Treatment for Metastatic Prostate Cancer, The PREDICT Trial (PREDICT)
Rana McKay, MD - rmckay@health.ucsd.edu
NCT06632977
Inclusion Criteria:
* PRE-REGISTRATION: Histological or cytological evidence of prostate cancer. Patients with variant histologies including neuroendocrine, small cell and sarcomatoid prostate cancer are allowed to enroll and these will not be used as selection criteria for individual arms. Central pathology review is not required.
* PRE-REGISTRATION: Measurable disease and/or non-measurable metastatic disease per RECIST version 1.1.
* PRE-REGISTRATION: Tissue procured within 12 months of pre-registration (metastatic disease preferred over primary tissue, though both are acceptable) available for submission per Section 6.2. For patients who have progressed on A032102 and are pre-registering again, repeat tissue procurement will not be mandated.
* PRE-REGISTRATION: Molecular report available performed as part of standard of care testing via any Clinical Laboratory Improvement Act (CLIA)-certified next generation sequencing (NGS) assay. Patients may be assigned based on pre-determined qualifying molecular/DNA alterations as stated in Section 4.8 after receipt of local molecular testing by the A032102 molecular tumor board (MTB). Final determination of arm assignment will be determined by the MTB. For qualifying DNA alteration determined by the MTB, testing may be from tumor tissue collected at any time or circulating tumor DNA (ctDNA) within 12 months of pre-registration. If no qualifying DNA alteration is identified based on the CLIA-certified next generation sequencing assay and MTB review, Caris testing, should be performed for both DNA/RNA profiling. Arm assignment based RNA requires testing of tumor tissue collected within 12 months of pre-registration and MTB review.
* PRE-REGISTRATION: Age ≥ 18 years.
* REGISTRATION: Progressive mCRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND one or more of the following criteria (choose all the apply):
* PSA progression, defined by at least 2 consecutive rising PSA values at a minimum of 1-week intervals with the most recent PSA value being 2.0 ng/mL or higher, if confirmed PSA rise is the only indication of progression. Patients who received an anti-androgen must have PSA progression after withdrawal of anti-androgen therapy.
* Radiographic progression per RECIST 1.1 criteria for soft tissue lesions
* Bone metastasis progression per Prostate Cancer Working Group 3 (PCWG3) criteria.
* REGISTRATION: Patients selected to receive lutetium Lu 177 vipivotide tetraxetan treatment are required to have prostate-specific membrane antigen (PSMA) positive mCRPC as determined by investigator assessment. For reference, in the VISION trial this was defined as at least 1 PSMA+ metastatic lesion (defined as uptake greater than that of liver parenchyma in lesions of any size in any organ system) and no PSMA- lesions (defined as uptake equal to or lower than that of liver parenchyma in any lymph node with a short axis of at least 2.5 cm, in any solid organ lesion with a short axis of at least 1.0 cm, or in any bone lesion with a soft-tissue component of at least 1.0 cm in the short axis).
* REGISTRATION: Prior treatment with androgen receptor signaling inhibitor (ARSI) in either the metastatic hormone sensitive setting or mCRPC is required. Prior taxane therapy in either metastatic hormone sensitive setting or mCRPC is mandated unless patient is taxane ineligible or the patient refuses taxane therapy. Prior lutetium LU177 vipivotide tetraxetan treatment is permitted but not mandated. Patients with known germline or somatic deleterious BRCA 1/2 mutations must have received a prior PARPi.
* REGISTRATION: Resolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to \> grade 2 for at least 3 months prior to registration and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of:
* Chemotherapy-induced neuropathy
* Fatigue
* Residual toxicities from prior treatment: Grade 1 or grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism. type I diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation (vitiligo)
* REGISTRATION: No cytotoxic, biologic, radiopharmaceutical or other non-kinase inhibitor investigational agent within 4 weeks of registration. Treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitor) within 2 weeks of registration. Treatment with abiraterone acetate, apalutamide, or darolutamide within 2 weeks of registration. Treatment with enzalutamide within 4 weeks of registration. No treatment with radiation therapy within 2 weeks of registration.
* REGISTRATION: No major surgery within 4 weeks of registration.
* REGISTRATION: No prior treatment with EZH inhibitors.
* REGISTRATION: Prior treatment with cabazitaxel + carboplatin.
* REGISTRATION: None of the following conditions:
* Current use of moderate or strong cytochrome P450 (CYP)3A inducers.
* Known or suspected hypersensitivity to valemetostat tosylate (DS-3201b) or any of the excipients.
* 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.
\* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to registration after radiotherapy or at least 4 weeks prior to registration after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before registration.
* Significant cardiovascular defined as:
* Myocardial infarction within 6 months prior to enrollment.
* Uncontrolled angina pectoris within 6 months prior to enrollment.
* New York Heart Association Class 3 or 4 congestive heart failure.
* Corrected QT interval calculated by the Fridericia\'s formula (QTcF) ≥ 470 ms per electrocardiogram (ECG) within 42 days before randomization in any individual with any history of any cardiac disease or medication which can impact QTcF. Patients with known history or current symptoms of cardiac disease, history of treatment with cardiotoxic agents, or agents/conditions known to impact QTcF should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and ECG.
* Uncontrolled hypertension (resting systolic blood pressure \>160 mmHg or diastolic blood pressure \> 100 mmHg).
* Clinically significant acute infection requiring systemic antibacterial, antifungal or antiviral therapy.
* Moderate to severe hepatic impairment (Child-Pugh Class C)
* REGISTRATION: No freezing or donating sperm ≤ 14 days prior to registration.
* REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* REGISTRATION: No granulocyte colony-stimulating factor (GCSF) within 2 weeks of registration.
* REGISTRATION: No red blood cell (RBC) transfusions within 2 weeks of registration.
* REGISTRATION: No platelet transfusions within 2 weeks of registration.
* REGISTRATION: No bleeding diathesis.
* REGISTRATION: White blood cell count (WBC) ≥ 2,500/mcL.
* REGISTRATION: Absolute neutrophil count (ANC) ≥ 1,500/mcL.
* REGISTRATION: Hemoglobin ≥ 9 g/dL.
* REGISTRATION: Platelet count ≥ 100,000/mcL.
* REGISTRATION: Creatinine clearance ≥ 30 mL/min as defined by Cockcroft-Gault equation.
* REGISTRATION: Total bilirubin ≤ 1.5 x ULN (≤ 3 x upper limit of normal \[ULN\] for subjects with documented Gilbert\'s disease).
* REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
* REGISTRATION: Albumin ≥ 2.8 g/dL.
* REGISTRATION: The A032102 molecular tumor board will review the local pathology report and molecular sequencing report, and the Alliance registration/randomization office will relay the assignment to the submitting site. Once the site receives this assignment, they can register the patient to A032102. Any questions about the molecular board treatment assignments can be directed to A032102@alliancenctn.org.
* RE-REGISTRATION: Progressive mCRPC (after receiving the tumor board assigned therapy) as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease defined by radiographic progression on conventional imaging (CT/MRI chest, abdomen and pelvis and bone scan within 42 days of re-registration).
* RE-REGISTRATION: Resolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) resolved to CTCAE version 5.0, grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable grade 2 toxicities (defined as no worsening to \> grade 2 for at least 3 months prior to registration and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, comprised of:
* Chemotherapy-induced neuropathy
* Fatigue
* Residual toxicities from prior treatment: Grade 1 or grade 2 endocrinopathies which may include: Hypothyroidism/hyperthyroidism. type I diabetes, hyperglycemia, adrenal insufficiency, adrenalitis, skin hypopigmentation (vitiligo).
* RE-REGISTRATION: None of the following conditions:
* Imminent or established spinal cord compression based on clinical and/or imaging findings.
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to registration after radiotherapy or at least 4 weeks prior to re-registration after major surgery (e.g., removal or biopsy of brain metastasis). Patients must have complete wound healing from major surgery or minor surgery before re-registration.
* Corrected QT interval calculated by the Fridericia\'s formula (QTcF) \< 470 ms per ECG within 42 days before randomization in any individual with any history of any cardiac disease or medication which can impact QTcF.
* Significant cardiovascular defined as:
* Myocardial infarction within 6 months prior to enrollment.
* Uncontrolled angina pectoris within 6 months prior to enrollment.
* New York Heart Association Class 3 or 4 congestive heart failure.
* Uncontrolled hypertension (resting systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
* RE-REGISTRATION: ECOG Performance Status 0-2.
* RE-REGISTRATION: No GCSF within 2 weeks of registration.
* RE-REGISTRATION: No RBC transfusions within 2 weeks of registration.
* RE-REGISTRATION: No platelet transfusions within 2 weeks of registration.
* RE-REGISTRATION: WBC ≥ 2,500/mcL.
* RE-REGISTRATION: ANC ≥ 1,500/mcL.
* RE-REGISTRATION: Hemoglobin ≥ 9 g/dL (transfusions permitted).
* RE-REGISTRATION: Platelet count ≥ 100,000/mcL.
* RE-REGISTRATION: Creatinine clearance ≥ 30 mL/min as defined by Cockcroft-Gault equation.
* RE-REGISTRATION: Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN for subjects with documented Gilbert\'s disease).
* RE-REGISTRATION: AST and ALT ≤ 3 x ULN.
* RE-REGISTRATION: Albumin ≥ 2.8 g/dL.
* RE-REGISTRATION: QT Interval (QTcF) \< 470 ms (in individuals with any cardiac history of any medication or condition known to impact QTcF).
* RE-REGISTRATION: The A032102 molecular tumor board will review the CARIS molecular sequencing report, the Alliance registration/randomization office will relay the assignment to the site. Any questions about the molecular board treatment assignments can be directed to A032102@alliancenctn.org.
Exclusion Criteria:
\- OTHER: Genetic testing, DRUG: Valemetostat Tosylate, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Computed Tomography, PROCEDURE: Bone scan, PROCEDURE: FDG-Positron Emission Tomography, PROCEDURE: PSMA PET Scan, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cabazitaxel, DRUG: Abiraterone Acetate, DRUG: Enzalutamide, DRUG: Lutetium Lu 177 Vipivotide Tetraxetan
Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
Comparison of EVAR and ESAR for Infrarenal Aortic Aneurysms With a Wide Proximal Neck (HERCULES)
Suzanne Holewijn, PhD - herculestrial@rijnstate.nl
NCT05484115
Inclusion Criteria:
* Age 18 years or older
* Provided written informed consent
* Clinical necessity for treatment of the AAA, according to the current guidelines in the geographies participating
* Elective repair
* Eligible anatomy for treatment with the Endurant II/IIs stent graft system and Heli-FX EndoAnchor system according to the IFU of both devices
* Infrarenal neck diameter ≥ 28 mm and ≤32 mm
* Proximal neck length ≥10mm
Exclusion Criteria:
* Anatomy outside the IFU of the ndurant II/IIs stent graft system and Heli-FX EndoAnchor system
* Planned use of AUI main body device
* Patient is participating in another clinical study, potentially conflicting with the outcomes of the current study.
* Patient with eGFR \< 30 ml/min/1.73m2 before the intervention
* Patient's life expectancy \<2 years as judged by the investigator
* Patient has a psychiatric or other condition that may interfere with the study
* Patient has a known allergy to any device component
* Patients with a systemic infection who may be at increased risk of endovascular graft infection.
* Patient has a coagulopathy or uncontrolled bleeding disorder
* Patient has a ruptured, leaking, or mycotic aneurysm
* Patient is not eligible for standard EVAR
* Patient had a Cerebro Vascular Accident (CVA) or a myocardial infarction (MI) within the prior three months
* Patient is pregnant (Female patients of childbearing potential only)
* Patient has active COVID-19 infection or has been diagnosed with long COVID-19 requiring hospitalization within the 6 months prior to procedure.
* Patient has previously been treated with stent grafts in the aorto-iliac arteries DEVICE: endovascular aneurysm repair (EVAR) using the Endurant II/IIs stent graft system, DEVICE: endosuture aneurysm repair (ESAR) using Heli-FX EndoAnchor system
Aortic Aneurysm, Abdominal
AAA, Endovascular treatment, Wide proximal neck, EndoAnchors, Infrarenal, EVAR (Endovascular aneurysm repair), ESAR (Endosuture aneurysm repair), Endurant II/IIs stent graft system, Heli-FX EndoAnchor system
Selinexor With Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients
Study Coordinator - dfunes@wakehealth.edu
NCT02835222
Inclusion Criteria:
* Patients must have histologically or cytologically documented newly diagnosed de novo Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea,cytarabine and ATRA previous treatments are acceptable.
* Patients with core binding factor acute myeloid leukemia (AML) (ie AML with t(8;21) or t(16;16) or i16) are not eligible.
* Patients must not have a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, CMML or MDS not treated with a hypomethylating agent) however history of previous MDS treated with a hypomethylating agent IS allowed.
* Patients with de novo AML must not have partial or total monosomy 5 or 7 or i(17q) or t(17p). Negative FISH studies are sufficient for enrollment (i.e. FISH for -5, -7, +8, inv(16), t(8;21) and 17p).
* Patients must not have mutated FLT3 (either ITD OR TKD mutations).
* Hydroxyurea, leukapheresis or cytarabine may be used to control leukocytosis, provided that it is without Grade \>2 non-hematologic toxicity, and can be taken until start of therapy.
* Age \>18 years.
* ECOG performance status of ≤ 2 and fit for induction therapy in the opinion of the treating physician.
* Laboratory values ≤2 weeks must be:
* AST(SGOT)/ALT(SGPT)≤ 2.5 X institutional upper limit of normal
* Bilirubin ≤ 2 X ULN (3X if known history of Gilbert'syndrome)
* Creatinine clearance (CrCl) must be \> 20 mL/min
* Baseline left ventricular ejection fraction of at least 40% by MUGA or ECHO.
* Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
* Ability to understand and the willingness to sign an IRB-approved informed consent document.
Exclusion Criteria:
* Patients who have received any therapy other than hydroxyurea, cytarabine or ATRA with the purpose of treating their AML or patients with core binding factor AML or Acute Promyelocytic Leukemia are not eligible.
* Patients with a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, CMML or MDS not treated with a hypomethylating agent) however history of previous MDS treated with a hypomethylating agent IS allowed.
* Patients having received prior radiotherapy, treatment with cytotoxic agents, treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 4 weeks prior to treatment with selinexor, or those who have not fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment).
* Patients with another active malignancy that requires treatment excluding non-melanoma skin cancers.
* Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.
* Patients with known central nervous system involvement should be excluded from this clinical trial because the penetration of selinexor into the CNS is not currently known.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor.
* Uncontrolled concurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with known HIV infection or hepatitis (Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy.
* Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
* Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
* Prior exposure to a SINE compound DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Selinexor
Untreated Adult Acute Myeloid Leukemia