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Combining Radiation Therapy With Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck
ctrrecruit@vcu.edu
NCT05721755
Inclusion Criteria:
* STEP 1 REGISTRATION:
* Patient must be \>= 18 years of age
* Patient must have biopsy-proven metastatic squamous cell carcinoma, originating in the oral cavity, larynx, oropharynx, or hypopharynx, with active disease present in both the head and neck and distant sites
* NOTE: The tumor from an oropharynx primary site must have known p16 status; p16 positive cancer of unknown primary is allowed as well, provided the disease presentation in consistent with a head and neck primary
* Patient can have prior surgical resection of a primary cancer in the head and neck at any previous time, however, residual/recurrent disease in the head and neck must be present on baseline imaging
* Any effects from prior cancer therapy for other diseases must be fully resolved and not pose a problem for giving the treatment on this trial
* Patient must have 4 or fewer metastatic sites prior to starting any treatment, with thoracic nodal disease considered a single site if encompassable in a tolerable radiotherapy hypofractionated field (i.e.,15 fractions or less)
* NOTE: Contiguous/adjacent metastases treatable in a single stereotactic field may be considered a single site
* NOTE: Patients with additional indeterminate findings such that the total number of metastatic sites would be more than 4 may be enrolled if a non-malignant etiology to these findings is a reasonable consideration
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patients must have measurable disease as follows:
* For patients who have not started any initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck and chest, and abdomen obtained within 28 days prior to Step 1 registration
* For patients who have started or completed their 3 cycles of initial systemic therapy (with pembrolizumab + chemotherapy) must have measurable disease documented by CT of the neck, chest and abdomen obtained within 28 days prior to the start of their initial systemic therapy
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Total bilirubin =\< institutional upper limit of normal (ULN). Patients with a total bilirubin \> 1.5 x ULN, that is attributed to confirmed Gilbert's syndrome, are allowed after consultation and approval from their treating physician (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional ULN (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Creatinine clearance: Glomerular filtration rate (GFR) \>= 50 mL/min/1.73m\^2 (for patients receiving carboplatin-based regimens, GFR \> 30 mL/min/1.73m\^2) (obtained =\< 28 days prior to Step 1 registration or prior to the start of any chemotherapy if on Arm T)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 1 registration are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with 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 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 on Arm S must have received chemoimmunotherapy
* Patients will be enrolled in the quality of life (QOL) study if the patient can read and understand English, Spanish, French or Chinese (simplified or traditional characters)
* NOTE: Sites cannot translate the associated QOL forms
* Patients of childbearing potential and/or sexually active patients must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. Patients of childbearing potential must continue contraceptive measures for 4 months after the last dose of protocol treatment and must not breastfeed while on study treatment through 4 months after the last dose of protocol treatment
* STEP 2 RANDOMIZATION:
* Patient must have ECOG performance status 0-2
* Patient must have completed 3 cycles of initial systemic chemotherapy
* For patients registered to Arm S on Step 1, patients must have at least stable disease after completing 3 cycles of pembrolizumab + chemotherapy
* Patient must have no signs of progression (complete response \[CR\]/partial response \[PR\] or stable disease \[SD\]) on restaging imaging (consisting of neck, chest, and abdomen CT). Restaging imaging must have been done after completion of initial systemic chemotherapy with pembrolizumab + chemotherapy on Step 1 and within 7 days prior to step 2 randomization. Patients with stable or responding radiologic response are eligible for Step 2
Exclusion Criteria:
* Patients must not have prior head and neck radiotherapy
* Patient must not have an active autoimmune disease (i.e., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, etc.) that has required systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) in past 2 years. Replacement therapy (i.e., thyroxine, insulin, physiologic corticosteroid replacement) is not considered a form of systemic treatment and is allowed
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 registration to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patient must not have received any live vaccine within 30 days prior to Step 1 registration and while participating in the study. Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist trademark are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Fluorouracil, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Pembrolizumab, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8
Nasal Steroids, Irrigation, Oral Antibiotics, and Subgroup Targeting for Effective Management of Sinusitis (NOSES)
Lead Project Coordinator - researchfammed@georgetown.edu
NCT06076304
Inclusion Criteria:
• 18-75 years old; AND are experiencing either:
• "persistent" symptoms or signs compatible with ARS or sinus infection lasting for 1-21 days without any evidence of clinical improvement (Symptoms include facial pain or pressure, facial congestion or fullness, nasal obstruction, nasal discharge, no or reduced sense of smell, fever ≤39°C or 102°F, headache, bad smelling breath, fatigue, ear pain or pressure, and dental pain); OR
• onset with worsening symptoms or signs characterized by the new onset of fever, headache, or increase in nasal discharge following a typical viral upper respiratory infection (URI) that lasted 5-6 days and were initially improving (''double-sickening'').
Exclusion Criteria:
* allergy or intolerance to penicillin
* received systemic antibiotic therapy in the past 4 weeks
* prior sinus surgery (cosmetic surgery, such as rhinoplasty, septal deviation, etc. are not exclusionary)
* complications of sinusitis (facial edema (swelling), cellulitis), or orbital, meningeal or cerebral signs)
* health care clinician determined IV (intravenous) antibiotics or hospital admission are required
* pregnancy or breastfeeding
* presence of a comorbidity or medication that may impair a patient's immune response as determined by a health care clinician
* hospitalization in past 5 days
* unable or unwilling to provide informed consent or comply with study protocol requirements
* fever \>39°C or 102°F today
* taking intranasal corticosteroids (INCS) regularly in the past two weeks and unwilling to stop its use while in the study; OR
* previously enrolled or participated in the feasibility phase or this stage of study DRUG: Amoxicillin/Clavulanate Potassium 875 MG-125 MG Oral Tablet, DRUG: Placebo, DRUG: Budesonide nasal spray, OTHER: C-reactive protein
Sinus Infection, Acute Sinusitis
sinusitis, antibiotics, intranasal corticosteroids, saline nasal irrigation, comparative effectiveness
Feasibility Study for the Comprehensive Overweight/Obesity Management Pre-Kidney Transplant (COMPKT) Program
Evan Sisson - emsisson@vcu.edu
NCT06688825
Inclusion Criteria:
* on the waiting list for kidney transplant at VCUHS
* BMI greater than 35 kg/m2
Exclusion Criteria:
* Children, prisoners, pregnant women BEHAVIORAL: Education regarding Weight loss, BEHAVIORAL: Lifestyle tools for weight loss, BIOLOGICAL: Blood draw
Kidney Transplant, Complications, Obesity
Long-Term Development of Muscular Dystrophy Outcome Assessments (GRASP-01-005)
Jennifer Raymond - Jennifer.Raymond@vcuhealth.org
NCT05989620
Inclusion Criteria:
• Age between 6-50 years at enrollment
• Clinically affected (defined as weakness on bedside evaluation in a pattern consistent with proximal weakness)
• Genetic confirmation of a LGMD, DM2, or LOPD
• FVC above 30% of predicted
Exclusion Criteria:
• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator
• Participation in a clinical trial receiving an investigational product
LGMD1B, LGMD1C, LGMD1D, LGMD1E, LGMD1F, LGMD1G, LGMD1H, LGMD2A, LGMD2B, LGMD2C, LGMD2D, LGMD2E, LGMD2F, LGMD2G, LGMD2I, LGMD2J, LGMD2K, LGMD2L, LGMD2M, LGMD2N, LGMD2O, LGMD2P, LGMD2Q, LGMD2S, LGMD2T, LGMD2U, LGMD2W, LGMD2X, LGMD2Y
Muscular Dystrophy, Myotonic Dystrophy, Limb Girdle Muscular Dystrophy, LGMD, LOPD, Late Onset Pompe Disease
Functional Outcomes in CondUction System Pacing and Right Ventricular Synchrony (FOCUS-Right) (FOCUS-Right)
Ajay Pillai - ajay.pillai@vcuhealth.org
NCT06601322
Inclusion Criteria:
* presence of dual chamber LBBAP implantation
* presence of anodal capture with bipolar pacing configuration as determined at pacing implant.
Exclusion Criteria:
* Known history of chronotropic incompetence
* high degree or complete heart block
* inability to tolerate NVP during initial device interrogation
* pregnancy
* inability to undergo MRI or exercise utilizing supine bicycle at target work-load
* presence of MRI unsafe pacemaker components. OTHER: Pacemaker Interrogation and Electrocardiogram (ECG):, OTHER: Cardiopulmonary Exercise Test (CPET) and Exercise Stress Cardiac Magnetic Resonance (ExeCMR, OTHER: Continuous pacemaker telemetry (CPT)
Left Branch Bundle Block, RV - Right Ventricular Abnormality
Pacemaker, CPET-CMR
Phase Ib/2a Drug-drug Interaction Study of a Combination of 45mg Dextromethorphan With 105 mg Bupropion
Tiffany Pignatello - Tfitz@vcu.edu
NCT05976646
Inclusion Criteria:
* Males and female subjects between 18 - 65 years of age;
* Understand the study procedures and provide written informed consent in the English language.
* Meet current DSM-5 criteria for OUD, of at least moderate severity, currently engaged in MOUD treatment at a buprenorphine-naloxone sublingual film total daily dose ranging from 8mg/2mg to 24mg/6mg or buprenorphine sublingual tablet 5.7mg/1.4mg to 17.1/4.3 daily for at least 2 weeks at screening. Or on a stable dose of depot injectable buprenorphine for at least four months, with at least one week since last depot buprenorphine injection.
* Have a positive urine drug screen for buprenorphine during screening and upon presenting for the first laboratory day on the clinical research unit to document buprenorphine use;
* Quick Inventory of Depressive Symptomatology (16-Item) (QIDS-SR16) score of mild or greater (\>6)
* Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (ie., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal), participants must agree to use an acceptable form of contraception during study participation and to continue its use for at least 30 days after the last dose of the study drug (e.g, abstinence, intrauterine device, hormonal implant, hormonal patch/ring/pill, condoms (male or female).
Exclusion Criteria:
* Contraindications for participation as determined by medical history and physical exam performed by study NP or study physician;
* Pregnant or nursing women;
* Baseline ECG with clinically significant abnormal conduction;
* Uncontrolled serious psychiatric or major medical disorder; including uncontrolled hypertension, seizure disorder, anorexia nervosa or bulimia, bipolar disorder, schizoaffective disorder, or schizophrenia;
* Taking antidepressant medications (tricyclic antidepressants, SSRIs, SNRIs, MAOIs), antibiotic linezolid, antiepileptics, or CNS stimulants (amphetamine, methylphenidate) within the two weeks prior to initiation of study medication
* History of adverse reaction or allergy to dextromethorphan or bupropion
* Current severe alcohol use disorder or current benzodiazepine use or recent (within last 3 months) discontinuation of alcohol with severe alcohol use disorder or discontinuation of benzodiazepines with severe benzodiazepine use disorder
* Current DSM-5 diagnosis of any psychoactive substance use disorder other than opioids, cocaine, marijuana, or nicotine, or mild or moderate alcohol use disorder. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
* Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months.
* Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. DRUG: Placebo, DRUG: Auvelity
Addiction, Opioid Use, Substance Use Disorders, Opioid Use Disorder
Brain Oxygen Optimization in Severe TBI, Phase 3 (BOOST3)
William Barsan, MD - wbarsan@umich.edu
NCT03754114
Inclusion Criteria:
* Non-penetrating traumatic brain injury
* Glasgow Coma Scale (GCS) 3-8 measured off paralytics
* Glasgow Coma Scale motor score \< 6 if endotracheally intubated
* Evidence of intracranial trauma on CT scan
* Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
* Able to place intracranial probes and randomize within 12 hours from injury
* Age greater than or equal to 14 years
Exclusion Criteria:
* Non-survivable injury
* Bilaterally absent pupillary response in the absence of paralytic medication
* Contraindication to the placement of intracranial probes
* Treatment of brain tissue oxygen values prior to randomization
* Planned use of devices which may unblind treating physicians to brain tissue hypoxia
* Systemic sepsis at screening
* Refractory hypotension
* Refractory systemic hypoxia
* PaO2/FiO2 ratio \< 150
* Known pre-existing neurologic disease with confounding residual neurological deficits
* Known inability to perform activities of daily living (ADL) without assistance prior to injury
* Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
* Pregnancy
* Prisoner
* On EFIC Opt-Out list as indicated by a bracelet or medical alert OTHER: ICP + PbtO2 guided management strategy, OTHER: ICP guided management strategy
Brain Injuries, Traumatic
intracranial pressure, hypoxia, brain, critical care, emergency treatment, monitoring, physiologic
A Study of ZN-c3 in Women With Recurrent or Persistent Uterine Serous Carcinoma
Project Director - medicalaffairs@zentalis.com
NCT04814108
INCLUSION CRITERIA
• Females ≥18 years of age at the time of informed consent.
• Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject. * Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible. * Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
• Measurable disease per RECIST Guideline Version 1.1
• Required prior therapy for endometrial cancer:
• Treatment with a platinum-based chemotherapy regimen.
• Treatment with a PD-(L)1 inhibitor
• Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
• Adequate hematologic and organ function EXCLUSION CRITERIA
• Any of the following treatment interventions within the specified time frame prior to C1D1:
• Major surgery within 28 days
• Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
• Radiation therapy within 21 days;
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
• Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
• A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.
• Females ≥18 years of age at the time of informed consent.
• Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject. * Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible. * Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
• Measurable disease per RECIST Guideline Version 1.1
• Required prior therapy for endometrial cancer:
• Treatment with a platinum-based chemotherapy regimen.
• Treatment with a PD-(L)1 inhibitor
• Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
• Adequate hematologic and organ function EXCLUSION CRITERIA
• Any of the following treatment interventions within the specified time frame prior to C1D1:
• Major surgery within 28 days
• Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
• Radiation therapy within 21 days;
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter).
• Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
• A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.
DRUG: ZN-c3
Uterine Serous Carcinoma
uterus, uterine, endometrial, endometrium, serous carcinoma, wee1, Wee-1, usc, Uterine Serous Carcinoma, serous
Pre-Operative Window of ET to Inform RT Decisions (POWER II) (POWER II)
Meagan Miller - aey8fc@uvahealth.org
NCT06507618
Inclusion Criteria (summary):
* Diagnosis of ER+, PR +/-, and HER2- non amplified invasive breast cancer and clinically negative nodes
* ECOG performance status 0-2
* Females, aged ≥ 65 years
* Patient is eligible for BCS and opted for BCS
* Patient is a candidate for radiation therapy
* Patient is a candidate for endocrine therapy (tamoxifen or an aromatase inhibitor)
* Ability to take oral medication and be willing to adhere to endocrine therapy for the 3-month period prior to BCS
* Agreement to adhere to Lifestyle Considerations (details in protocol) throughout study duration
* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria:
* Bilateral synchronous breast cancer
* Multicentric disease
* Prior use of Tamoxifen or aromatase inhibitors
* History of ipsilateral breast radiation therapy
* Has a known additional malignancy that is progressing and/or requires active treatment with cytotoxic chemotherapy or radiation therapy. Malignancies deemed stable and low risk for complication per investigator's judgment may be allowed after discussion with multi-site PI.
* Current or planned use of a strong CYP2D6 inhibitor (e.g., Fluvoxamine, Paroxetine) and is not able to receive an endocrine therapy agent that does not use the CYP2D6 pathway. DRUG: Tamoxifen, Letrozole, Anastrozole, or Exemestane
Breast Cancer Female
breast cancer, endocrine therapy, radiation, letrozole, anastrozole, exemestane, tamoxifen, survey, questionnaire, geriatric
Testing Whether the Addition of Carboplatin Chemotherapy to Cabazitaxel Chemotherapy Will Improve Outcomes Compared to Cabazitaxel Alone in People With Castrate-Resistant Prostate Cancer That Has Spread Beyond the Prostate to Other Parts of the Body
ctrrecruit@vcu.edu
NCT06470243
Inclusion Criteria:
* STEP 1 SCREENING REGISTRATION: NOTE: All participants must have biopsy tissue submitted to MD Anderson Cancer Center prior to randomization for alteration assessment. Participants must have determination of their AVPC-Molecular Pathologic Signature immunohistochemistry (MSIHC) status from central assessment by the MD Anderson Clinical Pathology Laboratory using Clinical Laboratory Improvement Act (CLIA) certified immunohistochemistry (IHC) assays for TP53, RB1 and PTEN. In addition, while not mandated, CLIA certified next generation sequencing (NGS) of tumor deoxyribonucleic acid (DNA) and/or circulating tumor derived DNA (ctDNA) assessment of AVPC-MS marker status will be collected from participants for whom it is available
* STEP 1 SCREENING REGISTRATION: Participants must have a histologically confirmed diagnosis of prostate cancer at the time of step 1 registration
* STEP 1 SCREENING REGISTRATION: Participants must have castrate-resistant prostate cancer and metastatic disease by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node)
* STEP 1 SCREENING REGISTRATION: Participants may have received any prior therapy, but one must be docetaxel or contain docetaxel in either the castrate-sensitive and/or castrate resistant disease state
* STEP 1 SCREENING REGISTRATION: Participants must be ≥ 18 years of age at the time of step 1 screening registration
* STEP 1 SCREENING REGISTRATION: Participants must have solid tumor biopsy material (formalin-fixed paraffin-embedded (FFPE) tissue blocks and/or 10 cut slides on four-micron thick unstained positive charged slides of FFPE tissue) available for submission for alterations in TP53, RB1 and PTEN by IHC using CLIA certified assays in the MD Anderson Clinical Pathology Laboratory. This specimen is required for central assessment of the AVPC-MSIHC regardless of whether the site has already locally evaluated the AVPC-MS status
* STEP 1 SCREENING REGISTRATION: Tumor samples submitted for analysis must have been collected within 12 months prior to step 1 screening registration. Samples from metastatic lesions collected in the castrate-resistant disease state are preferable but not mandatory. Samples obtained during the hormone-naive disease state are acceptable if collected within 12 months of step 1 screening registration. If more than one tumor sample exists, the sample obtained closest to the date of registration should be submitted to MDACC for analysis
* NOTE: Sites will receive an email from Southwest Oncology Group (SWOG) Statistics and Data Management Center containing participant results of Aggressive Variant Prostate Cancer Molecular Signature (AVPC-MS) assessment within 5-12 business days after tissue submission to MD Anderson Clinical Pathology Laboratory. The participant's AVPC-MS signature result (positive or negative) is required BEFORE randomization on to step 2. If sites receive a non-evaluable AVPC-MS signature result, SWOG Statistics and Data Management Center will provide instructions for resubmission
* STEP 1 SCREENING REGISTRATION: NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* STEP 1 SCREENING REGISTRATION: 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. Documentation of informed consent via remote consent is allowed
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2 RANDOMIZATION: NOTE: Participants must be registered to step 2 randomization within 70 days after registration to step 1. Participants must plan to start protocol therapy no more than 14 days after step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have castrate levels of testosterone with a baseline level \< 50ng/dL within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have evidence for metastatic prostate cancer by bone scan and/or CT/MRI (i.e., soft tissue, visceral, lymph node). Visceral and/or soft-tissue metastases must be ≥ 1.0 cm in diameter and lymph nodes must be \> 1.5 cm diameter in the short axis. Scans must be obtained within 28 days prior to randomization
* NOTE: All disease must be assessed and documented on the baseline/pre-registration tumor assessment form
* STEP 2 RANDOMZIATION: Participants must have progressive disease (PD) in the opinion of the treating investigator according to any of the following criteria
* Progression in measurable disease (RECIST 1.1 criteria). Patient with measurable disease must have at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) \[CT scan thickness no greater than 5 mm\] or magnetic resonance imaging (MRI). Lymph nodes should be ≥ 15 mm in short axis. Previously irradiated lesions, primary prostate lesion and bone lesions will be considered non-measurable disease
* Progression in bone as evidenced by:
* Appearance of 2 or more new bone lesions on bone scan (BS). If equivocal, they must be confirmed by other imaging modalities (CT; MRI), and/or repeat BS \> 4 weeks later
* Appearance of a new lytic lesion(s) and/or increasing size of an existing lesion by CT/MRI, since AVPC tumors may produce lytic bone lesions that are not detected on conventional bone scans
* Rising prostate-specific antigen (PSA) defined (Prostate Cancer Working Group 2 \[PCWG2\]) as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. In case of progression based on rising PSA only, the first rising PSA (measure 2) must be obtained within 6 months of initiation of androgen receptor (AR) targeted therapy (≤ 6 months)
* Clinical progression. Increasing symptoms unequivocally attributed to disease progression as judged by the treating physician
* STEP 2 RANDOMIZATION: Participants must not have received prior cabazitaxel or carboplatin
* STEP 2 RANDOMIZATION: Participants must not be receiving treatment on another therapeutic clinical trial at the time of randomization. Chemotherapies, bone targeting therapies, immunotherapies and clinical trial agents must be discontinued ≥ 21 days prior to randomization. Stereotactic radiation (SART) must be discontinued ≥ 3 days prior to randomization
* STEP 2 RANDOMIZATION: Participants must not be receiving radiation therapy or kyphoplasty-vertebroplasty within 14 days prior to randomization or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must not have untreated fractures and/or cord compression
* STEP 2 RANDOMIZATION: Participants must not have symptomatic uncontrolled brain metastases. Properly treated brain metastases (i.e., with stereotactic radiation) within 14 days are allowed
* STEP 2 RANDOMIZATION: Participants must have Zubrod performance status of 0 - 2 within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants must have a complete medical history and physical exam within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Platelets ≥ 100 x 10\^3/uL (unless clinical evidence of bone marrow infiltration by tumor in which case \> 75 x 10\^3/uL are allowed) (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Total bilirubin ≤ institutional upper limit of normal (ULN) with the exception of isolated hyperbilirubinemia due to Gilbert's syndrome or if the participant has liver metastases and/or acute tumor associated illness \< 4x ULN (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (or if participant has liver metastases and/or acute tumor-associated illness, ≤ 4x institutional ULN) (within 28 days prior to step 2 randomization)
* STEP 2 REGISTRATION: Participants must have a calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 randomization
* STEP 2 RANDOMIZATION: Participants with peripheral neuropathy must have ≤ grade 2 peripheral neuropathy (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) (within 28 days prior to step 2 randomization)
* STEP 2 RANDOMIZATION: Participants 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 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 vasectomy with testing showing no sperm in the semen
* STEP 2 RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the treatment regimen
* STEP 2 RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* STEP 2 RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the SWOG Specimen Tracking System PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabazitaxel, DRUG: Carboplatin, PROCEDURE: Chest Radiography, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, DRUG: Prednisone
Castration-Resistant Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8
A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
AskFirst Patient Engagement - AskFirst@askbio.com
NCT05230459
Inclusion Criteria:
• Male and female subjects aged 18 and 65 years with clinical diagnosis of LGMD2I/R9 and confirmation of FKRP gene mutation.
• Ability to walk/run 10 meters in \<30 seconds.
• Able to understand and comply with all study procedures.
• Sexually active females of childbearing potential and female and male partners of male subjects receiving study intervention must use a barrier method of contraception for the first 6 months after dosing.
Exclusion Criteria:
• Significant cardiomyopathy as defined by echocardiogram (left ventricular ejection fraction \<40%), evidence of conduction defect (increased PR and RR intervals, left bundle branch block and QTcF \>480m/sec), NYHA Class 3 or 4 heart failure, or MRI gadolinium enhancement evidence of clinically important myocardial fibrosis.
• Contraindication to MRI or hypersensitivity to contrast dyes, shellfish or iodine.
• Implanted spinal rods, cardiac pacemaker or other implantation that would distort cardiac MRI images.
• History of active, ongoing chronic liver disease (e.g. hepatitis, HIV-related liver disease, hemochromatosis, steatosis, etc.) or abnormal liver function tests (abnormal GGT and/or abnormal total/direct bilirubin \>upper limit of normal \[ULN\] and/or elevated AST and ALT \>2 ULN).
• Abnormal renal function (GFR \<60 ml/min, using the Modification of Diet in Renal Disease equation).
• Any life-threatening disease, including malignant neoplasms and medical history or malignant neoplasms within the past 5 years prior to screening (except basal and squamous cell skin cancer).
• In the opinion of the investigator, a pre-existing medical condition that predisposes the subject to risks that outweighs the potential benefits.
• Requirement for daytime ventilatory support.
• Change in glucocorticosteroid treatment within 3 months prior to screening visit.
• Exposure to another investigational drug within 3 months prior to study treatment or any previous treatment with gene therapy.
• Ongoing participation in any other therapeutic clinical trial.
• Neutralizing antibody titer to AAV9 \>1:5.
• Female subjects who are pregnant, plan to become pregnant in the next 12 months, or breastfeeding.
GENETIC: AB-1003 dose level 1, GENETIC: AB-1003 dose level 2, OTHER: Placebo
Limb Girdle Muscular Dystrophy, Limb-Girdle Muscular Dystrophy Type 2, LGMD2I, Muscular Dystrophy, LGMD2, LGMD, FKRP, FKRP Mutation, Fukutin Related Protein
gene therapy, LGMD2I, LGMD2I/R9, gene augmentation therapy, FKRP, fukutin related protein, FKRP mutation
Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma (STRASS2)
EORTC HQ - 1809@eortc.org
NCT04031677
• STRASS 2
Inclusion Criteria:
* Histologically proven primary high risk leiomyosarcoma (LMS) or Liposarcoma (LPS) of retroperitoneal space or infra-peritoneal spaces of pelvis.
* LMS:
* Any grade LMS can be included
* Minimum size of LMS tumor should be 5 cm
* LPS:
* Diagnosis should be confirmed based on MDM2 (Mouse double minute 2 homolog) and CDK4 (Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while proof of MDM2 amplification is highly recommended.
* All grade 3 DDLPS can be included.
* DDLPS with confirmed grade 2 on biopsy can be included when:
* The grade 2 DDLPS has an FNCLCC score=5 (Fédération Nationale des Centres de Lutte Contre Le Cancer), and clear necrosis on imaging (whether or not present on the biopsy).
* The tumors carry a high risk gene profile as determined by the Complexity INdex in SARComas (CINSARC-high)
* Unifocal tumour
* Resectable tumour: resectability is based on pre-operative imaging (CT-abdomen, potentially also with MRI) and has to be defined by the local treating sarcoma team. A patient is not considered resectable when the expectation is that only an R2 resection is feasible.
* Criteria for non-resectability are:
* Involvement of the superior mesenteric artery, aorta, coeliac trunk and/or portal vein
* Involvement of bone
* Growth into the spinal canal
* Progression of retro-hepatic inferior vena cava leiomyosarcoma towards the right atrium
* Infiltration of multiple major organs like liver, pancreas and or major vessels
* Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by imaging. CT thorax abdomen pelvis with IV contrast is the preferred imaging modality. In case of any contra-indications (medical or regulatory), it is allowed to perform a non-contrast CT thorax + MRI abdomen \& pelvis
* Collection of tumour tissue for central pathology review is mandatory.
* For patients with LMS: if there is not enough tissue for assessing the grading, this is acceptable.
* If tumour tissue is not available for the central pathology review, patient will not be eligible.
* If the biopsy was not done or the FFPE of the biopsy not available but at least 10 unstained slides or one pathological block are available for the central review, that will be considered as acceptable.
* For the biopsy if fine needle aspiration (FNA) is performed instead of core needle biopsy (CNB) recommended by the standard guidelines, please contact the EORTC medical monitors for further evaluation.
* Collection of tumour tissue and blood samples for translational research is mandatory.
* In case there is not enough tissue for TR, a new biopsy is not required and if the patient fulfils all other eligibility criteria, he/she will be eligible.
* If the blood samples are not collected, patient will not be eligible.
* If the patient refuses the collection of biomaterial for TR, patient will not be eligible even if he/she fulfils all other eligibility criteria
* ≥ 18 years old (no upper age limit)
* WHO performance status ≤ 2
* Adequate haematological and organ function
* American Society of Anaesthesiologist (ASA) score \< 3
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to randomization.
Note: a woman is considered of childbearing potential, i.e., fertile, if she is following menarche. She remains of childbearing potential until she becomes post-menopausal or permanently sterile.Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 consecutive months without menses, a single FSH measurement is insufficient.
* WOCBP in both arms should use highly effective birth control measures, during the study treatment period and for at least 6 months after the last dose of chemotherapy or date of surgery (except for women receiving chemotherapy with ifosfamide who should continue contraception until 1 year after last day of treatment). A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
* For men in the experimental arm: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm.
* Female subjects who are breast feeding should discontinue nursing prior to the first day of study treatment and until 6months after the last study treatment.
* Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Exclusion criteria:
* Sarcoma originating from bone structure, abdominal or gynecological viscera
* Extension through the sciatic notch or across the diaphragm
* Metastatic disease
* Any previous surgery (excluding diagnostic biopsy), radiotherapy or systemic therapy for the present tumour
* Hypersensitivity to doxorubicin, ifosfamide, dacarbazine or to any of their metabolites or to any of their excipients
* Congestive heart failure
* Angina pectoris
* Myocardial infarction within 1 year before randomization
* Uncontrolled arterial hypertension defined as blood pressure ≥ 150/100 mm Hg despite optimal medical therapy.
Note: in case of high blood pressure: 1) initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 2) blood pressure must be re-assessed on two occasions that are separated by a minimum of 1 hour. The mean SBP / DBP values from each blood pressure assessment must be ≤ 150/90mmHg in order for a patient to be eligible for the study.
* Uncontrolled cardiac arrhythmia
* Previous treatment with maximum cumulative doses (450mg/m² Doxorubicin or equivalent 900mg/m² Epirubicin) of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Active and uncontrolled infections
* Vaccination with live vaccines within 30 days prior to study entry
* Inflammation of the urinary bladder (interstitial cystitis) and/or obstructions of the urine flow.
* Other invasive malignancy within 5 years, with the exception of adequately treated non-melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer.
* Uncontrolled severe illness, infection, medical condition (including uncontrolled diabetes), other than the primary LPS or LMS of the retroperitoneum.
* Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control method.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial
* Known contraindication to imaging tracer and to MRI
• Selection criteria for STREXIT 2 * Patients with histologically proven primary resectable localized high-risk DDLPS or LMS of retroperitoneal space or infra-peritoneal spaces of pelvis (as described in the inclusion criteria of STRASS 2) and amenable to receive chemotherapy but for whom the list of eligibility criteria for the study is too restrictive (tumour grading not available, inadequate organ function, concomitant diseases) * Patients who meet all eligibility criteria of STRASS 2 but do not consent to randomization or are not enrolled for any other reason. * Patients enrolled in a Registry collecting data on primary RPS patients in the centres participating in STRASS 2 (e.g., RESAR) and who satisfy the above criteria.
• Selection criteria for preferences for neoadjuvant chemotherapy in STRASS 2 substudy All patients recruited to STRASS 2 in participating centres (Australia +/- international sites) that are able to read, comprehend and write in English at a sufficient level to complete study materials.
PROCEDURE: Surgery, DRUG: Preoperative chemotherapy
Retroperitoneal Sarcoma, Liposarcoma, Leiomyosarcoma
Testing Drug Treatments After CAR T-cell Therapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Erin Rogers - erogers@swog.org
NCT05633615
Inclusion Criteria:
* STEP 1: REGISTRATION: Participants must have a histologically confirmed diagnosis of diffuse large B-cell lymphoma or follicular lymphoma grade 3b or primary mediastinal large B-cell lymphoma (PMBCL)
* STEP 1: REGISTRATION: Participants with transformed DLBCL must have transformed DLBCL from follicular or marginal zone lymphoma
* STEP 1: REGISTRATION: Participant must have bi-dimensionally measurable systemic disease (at least one lesion with longest diameter \> 1.5 cm)
* STEP 1: REGISTRATION: Participants with secondary central nervous system (CNS) lymphoma (parenchymal, spinal cord, meningeal, cerebrospinal fluid involvement) must be asymptomatic from their CNS disease
* STEP 1: REGISTRATION: Participants must be registered for step 1 after they have signed institutional consent for CAR T-cell leukapheresis but prior to the start of lymphodepleting (LD) chemotherapy for commercial CAR T-cell product
* STEP 1: REGISTRATION: In the opinion of the enrolling physician, participants must be felt to be a candidate for CAR T-cell therapy with plans to be treated with Food and Drug Administration (FDA) approved commercially available CD19 CAR T-cell construct.
* Participants must qualify for commercially approved CD19 CAR T-cell therapy per FDA package insert.
* If the CAR T-cell product does not meet parameters to be given as an FDA approved product (i.e. does not meet specification criteria mandated by FDA and is infused under an expanded access protocol \[EAP\] or single participant investigational new drug \[IND\]) the participant will be taken off of study and no longer be eligible for step 2 randomization
* STEP 1: REGISTRATION: Participants are permitted to receive or have received 'bridging therapy' after CAR T-cell leukapheresis. However, participants must not receive polatuzumab vedotin, and/or mosunetuzumab as part of bridging therapy.
* Bridging therapy is defined as lymphoma directed therapy administered between leukapheresis and the start of LD chemotherapy. This includes cytotoxic chemotherapy (e.g.: bendamustine and rituximab \[BR\], rituximab, gemcitabine and oxaliplatin \[R-gem/ox\]), radiation, corticosteroids, as well as novel therapies such as BTK inhibitors (e.g.: Ibrutinib), immunomodulators (e.g.: lenalidomide), monoclonal antibodies (e.g.: rituximab, obinutuzumab, tafasitamab) antibody drug conjugates (e.g: loncastuximab), checkpoint inhibitors (e.g.: pembrolizumab, nivolumab), clinical trial treatments, etc.
* If a participant receives polatuzumab vedotin or mosunetuzumab as bridging they will ineligible to continue on step 1 registration portion of the study and be ineligible for step 2 randomization
* STEP 1: REGISTRATION: PET-CT scan must be planned for completion within 60 days prior to the start of LD chemotherapy.
* All pre-CAR T-cell therapy disease must be assessed and documented on the baseline/pre-registration tumor assessment form.
* If receiving bridging therapy, participants must have a PET-CT scan upon completion of all planned bridging therapy. If the PET-CT scan after completion of bridging therapy is consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* Participants are permitted to receive corticosteroids after leukapheresis without the need to repeat a PET-CT scan. If steroids are used, they must be planned to stop no later than 3 days before CAR -T cell infusion.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 1: REGISTRATION: Participants that have previously been treated with polatuzumab vedotin or mosunetuzumab prior to CAR T-cell leukapheresis for either indolent or aggressive NHL are eligible as long as the participant did not have refractory disease or progression/relapse within 6 months of the last infusion with either agent
* STEP 1: REGISTRATION: Participants must be planning to receive CAR T-cell infusion no earlier than 2 days and no later than 14 days after completion of the last day of lymphodepleting chemotherapy. Any participant receiving CAR T-cell infusion outside of this window will be ineligible for step 2 randomization
* STEP 1: REGISTRATION: LD chemotherapy prior to CAR T-cell infusion must be planned to start within 60 days after step 1 registration
* STEP 1: REGISTRATION: Participants must be \>= 18 years of age at the time of registration
* STEP 1: REGISTRATION: Participants must have Zubrod performance score (PS) of 0, 1, or 2
* STEP 1: REGISTRATION: Total bilirubin =\< 2 x institutional upper limit of normal (ULN) (within 14 days prior to registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 1: REGISTRATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 14 days prior to registration)
* STEP 1: REGISTRATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 14 days prior to registration. Estimated creatinine clearance is based on actual body weight
* STEP 1: REGISTRATION: Participants must have an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 60 days prior to registration with a cardiac ejection fraction \>= 40%.
* Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better.
* Participants must not have documented myocardial infarction and percutaneous coronary intervention (PCI) within 6 months prior to registration or myocardial infarction without PCI within 3 months of registration, or unstable angina
* STEP 1: REGISTRATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 1: REGISTRATION: Participants with hepatitis B virus infection must have undetectable viral load within 14 days prior to registration, be on suppressive therapy and have no evidence of hepatitis B virus (HBV) related hepatic damage
* STEP 1: REGISTRATION: Participants with hepatitis C infection must have eradication therapy completed, have no evidence of hepatitis C infection (HCV) related damage and have undetectable viral load within 14 days prior to registration
* STEP 1: REGISTRATION: Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* STEP 1: REGISTRATION: Participants must be offered the opportunity to participate in banking for planned translational medicine and future research. With participant consent, any residuals from the mandatory tissue submission will also be banked for future research.
* Note: Streck tubes must be ordered in advance. Please allow 5-7 days for shipment of the collection kits
* STEP 1: REGISTRATION: NOTE: As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2: RANDOMIZATION: Participants must have met all eligibility criteria for step 1 registration
* STEP 2: RANDOMIZATION: Participant's CAR T-cell product must have met specification parameters to be given as an FDA approved commercial product
* STEP 2: RANDOMIZATION: Participants must have a PET-CT scan between days 25-40 after CAR T-cell infusion and determined to have a response consistent with stable disease or partial remission by central review compared to most recent pre-LD chemo/CAR T-cell PET-CT scan.
* Note: Patients with delayed enrollment \> 21 days after 'day +30' PET-CT scan will necessitate a repeat PET-CT scan if concerning signs or symptoms of lymphoma progression develop.
* Note: If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Eligible participants must be randomized no later than 60 days after CAR -T infusion
* STEP 2: RANDOMIZATION: Participants must have started LD chemotherapy within 60 days of signing consent for step 1 registration
* STEP 2: RANDOMIZATION: Participants must have S2114 CAR T-cell therapy form submitted to Southwest Oncology Group (SWOG) prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants must have had a PET-CT scan upon completion of all planned bridging therapy if received, with the exception of up to 7 days of corticosteroids. If the PET-CT scan after completion of bridging therapy was consistent with complete remission per Lugano criteria as determined by enrolling physician, that participant will be ineligible for step 2 randomization.
* If response assessment by central review cannot be completed (I.e., poor quality of PET-CT scan, PET-CT performed out of window, etc.) this would be recorded as 'inadequate assessment' and patient would not be eligible for randomization
* STEP 2: RANDOMIZATION: Participants must have Zubrod PS of 0, 1, or 2
* STEP 2: RANDOMIZATION: Absolute neutrophil count (ANC) \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Total bilirubin =\< 2 x institutional ULN (within 7 days prior to step 2 randomization)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 2: RANDOMIZATION: AST and ALT =\< 3 x institutional ULN (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 7 days prior to step 2 randomization. Estimated creatinine clearance is based on actual body weight (within 7 days prior to step 2 randomization)
* STEP 2: RANDOMIZATION: Participants with peripheral neuropathy must have \< grade 2
* STEP 2: RANDOMIZATION: Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 2: RANDOMIZATION: Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 2 randomization and on suppressive therapy
* STEP 2: RANDOMIZATION: Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 2 randomization
* STEP 2: RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be continuing to receive anti-retroviral therapy and have an undetectable viral load test within 14 days prior to step 2 randomization
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have documented disease progression while on Arm 4 (observation) on this protocol. The follow-up tumor assessment form documenting disease progression must be submitted to SWOG prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must be registered within 28 days of the date of progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have imaging that clearly demonstrates progression compared to day +30 PET-CT scan
* Note: These scans should be performed as standard of care and only performed between scheduled response assessments required for study if symptoms arise that are concerning for progression
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants must have Zubrod PS of 0, 1, or 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): ANC \>= 1.0 x 10\^3/uL and participants must not have received myeloid growth factor within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Platelets \>= 75 x 10\^3/uL and participants must not have received platelet transfusion within 72 hours prior to this lab being drawn (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Total bilirubin =\< 2 x institutional ULN (within 14 days prior to step 3 crossover registration)
* Unless due to Gilbert's disease or lymphomatous involvement of liver
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): AST and ALT =\< 3 x institutional ULN
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Creatinine clearance \>= 40 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within days prior to step 3 crossover registration. Estimated creatinine clearance is based on actual body weight (within 14 days prior to step 3 crossover registration)
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with peripheral neuropathy must have \< grade 2
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with current symptoms of cardiac disease must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis B viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration and on suppressive therapy
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with history of hepatitis C viral infection must have undetectable viral load within 14 days prior to step 3 crossover registration
* STEP 3: CROSSOVER REGISTRATION (ARM 4 ONLY): Participants with known human immunodefici BIOLOGICAL: Axicabtagene Ciloleucel, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Fludarabine, BIOLOGICAL: Lisocabtagene Maraleucel, BIOLOGICAL: Mosunetuzumab, OTHER: Patient Observation, DRUG: Polatuzumab Vedotin, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tisagenlecleucel
Diffuse Large B-Cell Lymphoma, Grade 3b Follicular Lymphoma, Primary Mediastinal (Thymic) Large B-Cell Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Transformed Follic Lymph to Diff Large B-Cell Lymphoma, Transformed Marg Zone Lymph to Diff Large B-Cell Lymphoma
Evaluating the Impact of Social and Genetic Factors on Outcomes in Adolescent and Young Adult Cancer Survivors
ctrrecruit@vcu.edu
NCT06002828
Inclusion Criteria:
* Patient must be \>= 18 years of age at the time of registration
* Patient must have been between the ages of 15-39 at the time of their first primary cancer diagnosis of Hodgkin lymphoma or non-Hodgkin lymphoma (NHL)
* Patient must have completed therapy (with a complete response, per clinician determination) at the time of registration
* Patients last date of prior systemic therapy for first primary diagnosis for Hodgkin lymphoma or non-Hodgkin lymphoma must have been within one year prior to registration
* NOTE: Systemic therapy refers to all anti-cancer therapy, including but not limited to chemotherapy, intravenous (IV) or oral targeted medications, or radiation, and administered via a clinical trial or standard approach
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3
* Patient must be English speaking in order to be able to complete the required QOL forms on this study
* NOTE: Sites cannot translate the associated QOL forms
* Patient must not be receiving active therapy for Hodgkin lymphoma or non-Hodgkin lymphoma
* Patient must have internet access through computer, tablet, or smartphone
* Patient must have email address
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible PROCEDURE: Biospecimen Collection, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hodgkin Lymphoma, Non-Hodgkin Lymphoma
ULTRA-HFIB-Redo: Ultrasound-based Renal Sympathetic Denervation vs Control in Redo Ablation Patients
Jeff Lam, MS - jeff.lam@mountsinai.org
NCT05988411
Inclusion Criteria:
* Age ≥ 18;
* Planned for a redo AF ablation procedure (paroxysmal or persistent); (prior to randomization, a technically successful AF ablation procedure, defined as successful pulmonary vein isolation, if needed, as well as bidirectional block of any attempted anatomic lesion sets such as cavotricuspid isthmus line, roofline, mitral line and superior vena cava isolation, must have been completed). Note: the clinical recurrences must primarily be atrial fibrillation, and not atrial flutter/tachycardia (that is, a prospective patient may have a AFL/AT recurrences, but AF must be the dominant recurrent rhythm.)
* History of hypertension and either:
* Documented history of SBP≥160 or DBP≥100, or;
* Receiving ≥1 antihypertensive medication;
* Willingness to adhere to study restrictions and comply with all post-procedural follow-up requirements
Exclusion Criteria:
* Long-standing persistent AF (\>12 months); \>3 prior atrial fibrillation ablations (lifetime); AF ablation within 3 months of enrollment; extensive scar in left atrium.
* Individual with valvular AF or AF due to a reversible cause
* Prior treatment with other devices for hypertension including but not limited to ROX Coupler, Mobius stent, and/or the CVRx barostimulator device.
* NYHA class IV congestive heart failure;
* Individual has renal artery anatomy that is ineligible for treatment (as determined by renal angiography);
* Main renal artery diameter \<3mm or \>8.0 mm
* Main renal treatable artery length \< 20 mm (length may include proximal branches)
* Presence of renal artery stenosis of any origin ≥30%
* Calcification in renal arteries
* Prior renal denervation procedure
* Presence of abnormal kidney tumors
* Renal artery aneurysm
* Pre-existing renal stent or history of renal artery angioplasty
* Pre-existing aortic stent or history of aortic aneurysm
* Fibromuscular disease of the renal arteries
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Individual has an estimated glomerular filtration rate (eGFR) of less than 40mL/min/1.73m2, using the MDRD calculation;
* Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus, contraindication to all anticoagulation)
* Individual with known allergy to contrast medium not amendable to treatment.
* Life expectancy \<1 year for any medical condition
* Individual has experienced a myocardial infarction, unstable angina, cerebrovascular accident, or heart failure admission within 3 months of the baseline visit.
* Documented history of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis.
* Female participants who are pregnant or nursing.
* Individual has known secondary hypertension.
* Individual has a single functioning kidney (either congenitally or iatrogenically).
* Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
* Patients concurrently enrolled in any other investigational drug or device trial that would interfere with the conduction of this protocol. DEVICE: Renal Denervation, DEVICE: Catheter Ablation
Paroxysmal Atrial Fibrillation, Persistent Atrial Fibrillation
Comparing Brief Behavioral Therapy (BBT-CI) and Healthy Eating Education Learning (HEAL) for Cancer-Related Sleep Problems While Receiving Cancer Treatment
Brooke Burgess, MS - URCC_19185@urmc.rochester.edu
NCT04829539
Inclusion Criteria:
* Be at least 18 years of age
* Be diagnosed with cancer (stage I, II, III, or IV) with a life expectancy of at least 12 months
* Be currently receiving any cancer treatment (surgery alone is excluded)
* Report sleep disturbance of 3 or greater on the sleep disturbance question: "Rate your sleep disturbance in the past 2 weeks on a scale from 0-10, 0 is no problems and 10 is having the most severe problems"
* Have a score of 2, 1, or 0 on the Eastern Cooperative Oncology Group (ECOG) performance status scale
* Be able to speak, understand and read English to participate in the study assessments and interventions
Exclusion Criteria:
* Have a clinical diagnosis of obstructive sleep apnea or restless leg syndrome (even if controlled)
* Be engaged in a formal cognitive behavioral therapy for insomnia program presently or in the past 30 days. Use of sleep medications are allowed BEHAVIORAL: Behavioral Intervention, BEHAVIORAL: Behavioral Intervention, OTHER: Electronic Health Record Review, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration
Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Does a Periaqueductal Gray-vagus Nerve Interface Malfunction Explain the Nat hx With Its Numerous Co-morbidities?
Gisela Chelimsky - Gisela.Chelimsky@vcuhealth.org
NCT06616363
POTS sample
Inclusion Criteria:
* symptomatic ≥ 40 bpm rise in heart rate in the first 10 min of a tilt table study without a drop in blood pressure
* Clinical symptoms of orthostatic intolerance
Exclusion Criteria:
* Pregnant or breastfeeding
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic diseases
* Unstable medical conditions
* Use of narcotics
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
POST INFECTION
Inclusion Criteria:
* acute upper respiratory or gastrointestinal infection that required admission to the acute care units but not requiring an ICU stay
Exclusion Criteria:
* Pregnant or breastfeeding
* Chronic prescriptions, history of POTS or orthostatic symptoms, recent inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other unstable chronic diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software
HEALTHY CONTROLS
Inclusion Criteria:
* Apparently healthy with no known chronic illnesses
Exclusion Criteria:
* Pregnant or breastfeeding
* History of POTS or orthostatic symptoms, migraines, fibromyalgia, chronic fatigue, PTSD. Functional gastrointestinal disorders, fainting, dysmenorrhea, or other chronic pain syndrome, inpatient psychiatric admissions, substance use disorder, trauma such as a motor vehicle accident, surgery, or other significant physical or emotional trauma in the last 5 years
* Cognitive defects that preclude answering questionnaires or following assessment directions
* Other chronic unstable diseases
* Unstable medical conditions
* Use of narcotics
* Severe depression or anxiety (untreated / unstable)
* Limited English proficiency
* Investigator discretion that participant would not be suitable to participate
* A phone older than 5 years old or unable to support EMA software BEHAVIORAL: Questionnaires to be competed, BEHAVIORAL: Provide list of medication and lifetime events, BEHAVIORAL: Use phone App to record new life events, DEVICE: Will wear an activity monitor, OTHER: Periodic 24-hour urine sodium check, DIAGNOSTIC_TEST: A fMRI scan, DIAGNOSTIC_TEST: A bedside tilt test will be performed, OTHER: IV placed to collect blood samples, OTHER: Stool Sample
POTS - Postural Orthostatic Tachycardia Syndrome
PAG activation, Cardiovagal Modulation
Heuristic Tool To Improve Symptom Self-Management in Adolescents and Young Adults With Cancer
Grace Hodges - hodgesg@vcu.edu
NCT05958316
Inclusion Criteria:
* Has received at least 1 cycle of cancer treatment and is within 3 months of initial cancer diagnosis
* Receiving regularly scheduled cancer treatment and will be receiving at least three more cycles
* Reports at least 1 symptom related to cancer and/or its treatment
* Able to speak, read, and write English as required for completion of the C-SCAT and study measures
Exclusion Criteria:
\- Cognitive and/or physical inability to complete study measures. BEHAVIORAL: Computerized Symptom Capture Tool (C-SCAT) Intervention, BEHAVIORAL: Usual Care Control
Symptoms and Signs, Cancer, Childhood Cancer
Supportive Care, Symptom Management
Mobile Health for Adherence in Breast Cancer Patients
ctrrecruit@vcu.edu
NCT06112613
Inclusion Criteria:
* NON-PATIENT: Participants must be an oncology healthcare provider (i.e., oncologist, advanced practice provider, or oncology nurse)
* NON-PATIENT: Participants must have taken care of at least one patient randomized to Arm B (CONCURxP) who had less than 85% adherence rate at 12 months as measured by the WiseBag
* NON-PATIENT: Participant must speak English
* NON-PATIENT: Participant must be employed at an National Cancer Institute Community Oncology Research Program (NCORP) site for at least 6 months
* NON-PATIENT: Participant must be able to provide informed consent to participate in this study
* PATIENT STEP 0: Patient must be \>= 18 years of age
* PATIENT STEP 0: Patient must be fluent in written and spoken English OR patient must be fluent in written and spoken Spanish
* PATIENT STEP 0: Patient must present with new or established pathologically proven hormone receptor (HR)+ HER2- metastatic breast cancer at the time of Step 0
* PATIENT STEP 0: Patient must have initiated any of the CKD4/6 inhibitors (palbociclib or Ibrance, ribociclib or Kisqali, abemaciclib or Verzenio) within 30 days prior to consenting to Step 0 or have received a prescription order with stated intent to initiate within 30 days following Step 0 consent
* NOTE: Patients who have been treated previously with anticancer treatments other than CDK4/6 inhibitors are eligible
* NOTE: CDK4/6 inhibitors must be provided/supplied as a single agent blister pack. If the medication is supplied as capsules in a pill bottle (e.g., Ibrance capsules), patient is not eligible
* NOTE: Ribociclib (Kisqali) and abemaciclib (Verzenio) are only available in blister packs. Palbociclib (Ibrance) is the only CDK4/6 inhibitor that might be available in a capsule formulation. However, this is an outdated formulation and is rarely prescribed as a new start. The format of ordered palbociclib can be determined based on the prescription order
* PATIENT STEP 0: Patients must not have been previously treated with any of the following CDK4/6 inhibitors: Palbociclib or Ibrance, ribociclib or Kisqali, and abemaciclib or Verzenio
* PATIENT STEP 0: Patients must not already be enrolled in a therapeutic clinical trial that monitors CDK4/6 inhibitors
* PATIENT STEP 0: Patient must confirm that they intend to receive their care or monitoring at an NCORP site
* PATIENT STEP 0: Patient must have a personal mobile phone in which they are able and willing to send and receive text messages
* NOTE: The restriction to those with mobile phone access with text messaging is based on the primary intention of the study which involves the use of text messaging to improve adherence
* PATIENT STEP 0: Patient must have an email address
* NOTE: The restriction to those with an email address is based on the primary intention of the study which involves patients responding to questions regarding their reasons for non-adherence after every missed dose to improve adherence
* PATIENT STEP 0: Patient must have the ability to understand and the willingness to sign a written informed consent document
* NOTE: Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available are not eligible
* PATIENT STEP 0: Patient must not have an Eastern Cooperative Oncology Group (ECOG) performance status \>= 3 OR patient must not be deemed medically unable to participate in the study by the study investigators or an oncology clinician (i.e., referral to hospice)
* PATIENT STEP 0: Patient must not be enrolled in other trials offering financial assistance
* NOTE: Gift cards for survey completion, parking passes, or free medication provided as part of therapeutic trials are not considered financial assistance
* PATIENT STEP 1: Patient must meet all the eligibility criteria for Step 0
* PATIENT STEP 1: Patient must have signed a written informed consent form
* PATIENT STEP 1: Patient must have completed baseline survey within 30 days of the date of Step 0 Registration
* PATIENT STEP 1: Patients must have initiated their CDK 4/6 inhibitors within 30 days of the date of Step 0 registration OTHER: Electronic Health Record Review, OTHER: Health Promotion and Education, PROCEDURE: Health Telemonitoring, OTHER: Interview, BEHAVIORAL: Patient Navigation, OTHER: Survey Administration, OTHER: Text Message-Based Navigation Intervention
Anatomic Stage IV Breast Cancer AJCC v8, Breast Carcinoma, HER2-Negative Breast Carcinoma, Hormone Receptor-Positive Breast Carcinoma
Cardiovascular Health & Early Stress
Paula Rodriguez Miguelez - prodriguezmig@vcu.edu
NCT06557707
Inclusion Criteria:
Cohort 1
* Men and pre-menopausal women
* 18-30 years old
Cohort 2
* males and females
* 9-17 years old
Exclusion Criteria:
Cohort 1
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis
Cohort 2
* Evidence of cardiovascular, pulmonary, renal, hepatic or cerebral diseases
* Evidence of pregnancy or currently nursing.
* Having a history of chronic pain
* Having a history of rheumatoid arthritis OTHER: Childhood stress
Stress
Transdermal Rotigotine as Adjunct to Behavioral Therapy for Cocaine Use Disorder
Tiffany Pignatello, FNP - study4u@vcu.edu
NCT05886582
Inclusion Criteria:
* Male or female subjects between 25 and 70 years of age.
* Meet current DSM-5 criteria for Cocaine Use Disorder (CocUD), moderate or severe
* Able to understand and comply with study procedures
* Have positive urine result for cocaine metabolite benzoylecgonine (BE) during at least one screening visit (out of up to three visits, depending on participants' preference) AND/OR self-report of recent cocaine use (approximately past 30 days).
* Have hematology and chemistry laboratory tests that are within normal limits, except that liver function tests must be no more than 2x of the upper limit of normal (if any elevation is above the limit - must be judged by the study physician to be clinically insignificant).
* No clinically significant abnormalities on baseline ECG.
* Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory and fMRI testing.
* Women must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). Men will be advised to use condoms. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and the end of study participation.
* Body Mass Index (BMI) between 18-45kg/M2 and weight of at least 50kg at screening
Exclusion Criteria:
* Have concurrent secondary DSM-5 diagnosis of any psychoactive substance use disorder other than cocaine, alcohol, methamphetamine, nicotine, opioid, or marijuana use disorder.
* Have a DSM-5 axis I psychiatric disorder other than substance use disorder, including but not limited to Bipolar I Disorder, Schizophrenia, or other psychotic disorder that require treatment with antipsychotics, or a neurological disorder requiring ongoing treatment and/or making study participation unsafe. Comorbid PTSD, Generalized Anxiety Disorder and Major Depressive Disorder will be allowed.
* Consistent and regular (as opposed to intermittent, infrequent, or as needed) use of medications contraindicated for concurrent use along with RTG, or would confound the mechanism of RTG action and data interpretation. These include DA antagonists such as antipsychotic medications (especially neuroleptics) or metoclopramide.
* Subjects with evidence or history of any clinically significant medical disorder including biliary obstruction, clinically significant hepatic disease, severe cardiovascular or pulmonary disease, bronchial asthma, renal, or endocrine disease. However, controlled hypertension, controlled hypothyroidism, and cancer in remission over 5 years will not be excluded.
* Have a history of seizures (excluding childhood febrile seizures) or loss of consciousness (e.g. from traumatic brain injury) for more than 30 minutes.
* Have significant current suicidal or homicidal ideation or a suicide attempt within the past 6 months, based on the Columbia Suicide Severity Rating Scale (C-SSRS).
* Be HIV positive by self-report or history.
* Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and the end of study participation
* Have any other illness, or condition, which in the opinion of the clinical co-investigator (Arias) would preclude safe and/or successful completion of the study.
* Be allergic to rotigotine.
* Have taken any investigational drug within 45 days prior to baseline
* Demonstrate intolerance to, poor adherence to, or extreme skin irritation by daily application of known placebo "practice" skin patches during the screening phase
* Current/pending criminal charges that may result in incarceration within the next 60 days
* Self-report of allergic or other reactions to sulfites (e.g. in foods) DRUG: Rotigotine Transdermal System [Neupro], DRUG: Placebo
Substance-Related Disorders
Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)
Rachael Buckingham, BS - Rachael.buckingham@seattlechildrens.org
NCT05548283
Inclusion Criteria:
* All genders ≥ 6 years of age at Visit 1
* Documentation of a CF diagnosis
* Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
* At least one documented Pa positive culture within two years prior to Visit 1
Exclusion Criteria:
* Participant is not pregnant
* No known renal impairment or history of solid organ transplantation
* No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
* No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
* No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
* No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1 DRUG: Beta-lactam antibiotic, DRUG: Aminoglycoside
Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation
Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360
Comparing New Treatments for People With Newly Diagnosed Acute Myeloid Leukemia That Has an IDH2 Gene Change (A MyeloMATCH Treatment Trial)
ctrrecruit@vcu.edu
NCT06672146
Inclusion Criteria:
* Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have disease with a detectable IDH2 mutation based on central testing through the MYELOMATCH and be assigned to this clinical trial via MATCHBox prior to registration to this study
* Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH
* Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by having ≥ 20% blasts in the bone marrow and/or peripheral blood, excluding acute promyelocytic leukemia (APL) with PML-RARA
* Participants must not be receiving or planning to receive any other investigational agents while on protocol therapy
* Participants must not have received prior therapy for AML or myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN) with the exception of hydroxyurea, all-trans retinoic acid (ATRA), colony-stimulating factors, erythropoiesis-stimulating agents, immunosuppressive therapy, intrathecal chemotherapy, a single dose of cytarabine for cytoreduction, and/or leukapheresis
* Participants must not be currently receiving any cytarabine-containing therapy other than up to 1 g/m\^2 of cytarabine, which is allowed for urgent cytoreduction. The use of prior hydroxyurea, all-trans retinoic acid (ATRA), BCR-ABL directed tyrosine kinase inhibitor, erythropoiesis-stimulating agent, thrombopoietin receptor agonist and lenalidomide are allowed. Participants may receive hydroxyurea prior to treatment assignment on this substudy for cytoreduction but must agree to discontinue hydroxyurea prior to beginning treatment on this substudy
* White blood cell (WBC) must be \< 25 x 10\^9/L. Hydroxyurea, leukapheresis, and cytarabine \< 1 g/m\^2 are permitted to control the WBC prior to enrollment and initiation of protocol-defined therapy but must be stopped prior to initiation of protocol therapy
* Participants must be ≥ 60 years old; OR must be ≥ 18 years old and considered not eligible for cytarabine-based induction therapy
* Participants must have Zubrod Performance Status of 0-3 as determined by a history and physical (H\&P) exam completed within 14 days prior to registration
* Participants must have a complete medical history and physical exam within 14 days prior to registration
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's syndrome. Participants with history of Gilbert's syndrome must have total bilirubin ≤ 3 x institutional ULN (within 14 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN, unless considered to be elevated due to disease involvement (within 14 days prior to registration)
* Participants must have adequate kidney function as evidenced by creatinine clearance ≥ 30mL/min (by Cockcroft Gault) within 14 days prior to registration
* Participants must not have a baseline corrected QT interval ≥ 480 msec using Fridericia correction (QTcF).
* NOTE: Since older participants are at risk for prolonged QTc and may require supportive care with agents that affect QTc, an electrocardiogram (ECG) is recommended if clinically indicated. If the QTc is prolonged, they should be treated on MYELOMATCH TAP instead of MM1OA-S03
* Participants must have adequate cardiac function in the assessment of their treating physician. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2 or better
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications
* Participants must have agreed to have specimens submitted for translational medicine for MRD under MYELOMATCH and specimens must be submitted
* Enrollment to this treatment study requires prior enrollment into the myeloMATCH Master Protocol (MYELOMATCH). Participants enrolled in MYELOMATCH will submit bone marrow samples, peripheral blood samples, and buccal swabs to the Molecular Diagnostics Network (MDNet), the Clinical Laboratory Improvement Act (CLIA) laboratory network for myeloMATCH
* In addition to the MYELOMATCH specimens, there will be specimens obtained on treatment for this substudy. These specimens will be derived from procedures performed as part of standard assessments in the clinical care and management of AML with material being sent to the MDNet laboratories as specified. After performing the required tests on the specimens, the MDNet laboratories will send the residual material for biobanking and future research. Therefore, participants must be asked for their consent for the biobanking of specimens for future unspecified research. Participants may refuse this, but it is mandatory for sites to ask participants
* Participants must be offered the opportunity to participate in specimen banking
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Decitabine and Cedazuridine, DRUG: Enasidenib, DRUG: Venetoclax
Acute Myeloid Leukemia
Testing the Addition of the Anti-Cancer Drug Tivozanib to Immunotherapy (Pembrolizumab) After Surgery to Remove All Known Sites of Kidney Cancer (STRIKE)
Aishwarya Vijendran - guprotocols@alliancenctn.org
NCT06661720
Inclusion Criteria:
* • Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features following complete resection of the primary tumor (radical or partial nephrectomy)
* Note: Patients with microscopically positive soft tissue or vascular margins without gross residual disease are permitted
* Intermediate-high risk RCC:
* pT2 grade 4 or sarcomatoid features, N0M0
* pT3 any grade N0, M0
* High-risk RCC
* pT4, any grade, N0, M0
* pT, any stage., any grade, N+, M0
* cM1 no evidence of disease (NED) RCC
* Participants who have had resection of primary tumor (radical or partical nephrectomy) and resection or definitive radiation or ablation of solid, isolated, soft tissue metastases (excluding brain and bone lesions) at the time of primary tumor removal (synchronous) or ≤1 year from primary tumor removal (metachronous)
* Surgery (radical or partial nephrectomy or metastasectomy or ablation) \> 4 weeks but =\< 16 weeks prior to study registration with no ongoing complications from surgery
* No evidence of disease at time of randomization as assessed by investigator by either CT or MRI scan of the brain and chest, abdomen and pelvis
* No prior systemic treatment for RCC
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 8 g/dL
* Total bilirubin =\< 3 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x upper limit of normal (ULN)
* Calculated (calc.) creatinine clearance \>= 30 mL/min (using Cockcroft Gault equation or the estimated glomerular filtration rate from the modification of diet in renal disease trial)
* Urine protein =\< 1+ on urine analysis (UA) or urine protein creatinine ration (UPCR) \< 2mg/mg
* 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 pregnancy test is required =\< 14 days prior to registration
* HIV status: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Hepatitis
* Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with resolved HBV infection, defined as positive hepatitis B core antibody (anti-HBc) and negative hepatitis B surface antigen (HbsAg), are eligible
* Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Cardiac Disease: 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 IIB or better
* No history of myocarditis
* No history of clinically significant pneumonitis
* No uncontrolled hypertension (systolic blood pressure \[BP\] \> 150 mm Hg or diastolic BP \> 90 mm Hg) documented on 2 consecutive measurements taken at least 2 hours apart
* No serious non-healing wound, ulcer or bone fracture within 28 days prior to registration
* No serious/active infection requiring parenteral antibiotics
* No moderate or severe hepatic impairment (child-Pugh B or C)
* No significant bleeding disorders within 1 month prior to registration, for example:
* Hematemesis, hematochezia or other gastrointestinal bleeding grade 3 or higher
* Hemoptysis of pulmonary bleeding grade 3 or higher
* Hematuria or other genitourinary bleeding grade 3 or higher
* No history of allogeneic organ transplantation
* No history of allergy of hypersensitivity to study drugs or components
* No condition requiring systemic treatment with either corticosteroid (\> 10 mg daily or prednisone equivalent) within 14 days of treatment initiation or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids and adrenal replacement doses ≤10 mg daily prednisone equivalent are permitted in absence of active autoimmune disease
* No active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis or other gastrointestinal condition associated with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to registration
* 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 patients with a history of autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids \> 10 mg/day, or immunosuppressive drugs) with the following exceptions:
* Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
* Brief (\<7 days) use of systemic corticosteroids is allowed when use is considered standard of care
* Patients with vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy will not be excluded
* Patients requiring intermittent use of bronchodilators, inhaled steroids, or local steroid injections will not be excluded
* Patients with hypothyroidism that is stable with hormone replacement or Sjögren's syndrome will not be excluded • Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment BIOLOGICAL: Pembrolizumab, DRUG: Tivozanib, PROCEDURE: Biospecimen Collection, PROCEDURE: MRI, PROCEDURE: Computed Tomography, PROCEDURE: Biopsy, OTHER: Questionnaire Administration
Clear Cell Renal Cell Carcinoma, Renal Cell Carcinoma (RCC), Stage II Renal Pelvis Cancer AJCC v8, Stage III Renal Pelvis Cancer AJCC v8
A Study to Evaluate Del-brax (Also Referred to as AOC 1020) in Participants With FSHD (FORTITUDE-3)
Avidity Biosciences, Inc. - medinfo@aviditybio.com
NCT07038200
Inclusion Criteria:
* Clinical and genetic diagnosis of FSHD1 or FSHD2
* Ability to walk independently at pre-specified walking speed (orthoses and ankle braces allowed) for at least 10 meters at screening
* Adequate muscle strength based on QMT composite score
Exclusion Criteria:
* Breastfeeding, pregnancy, or intent to become pregnant during the study
* Unwilling or unable to comply with contraceptive requirements
* Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
* Blood Pressure \> 140/90 mmHg at Screening
* Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of the drug, whichever is longer
* Treatment with an oligonucleotide within 9 months of Screening DRUG: AOC-1020, DRUG: Placebo
Facioscapulohumeral Muscular Dystrophy, FSHD, FSHD - Facioscapulohumeral Muscular Dystrophy, FSHD1, FSHD2, Fascioscapulohumeral Muscular Dystrophy, Fascioscapulohumeral Muscular Dystrophy Type 1, Fascioscapulohumeral Muscular Dystrophy Type 2, Facioscapulohumeral Muscular Dystrophy 1, Facioscapulohumeral Dystrophy, Facio-Scapulo-Humeral Dystrophy, Facioscapulohumeral Muscular Dystrophy 2, Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1), FSH Muscular Dystrophy, Landouzy Dejerine Dystrophy, Landouzy-Dejerine Muscular Dystrophy, Landouzy-Dejerine Syndrome
Avidity, Avidity Biosciences, del-brax, del brax, delbrax, AOC1020, AOC 1020, delpacibart braxlosiran, FORTITUDE-3, FORTITUDE Phase 3, FORTITUDE, FORTITUDE 3
Effects of Lemborexant on Insomnia and Its Relationship to Mood and Behavior on Opioid Use Disorder Subjects
Joyce Ruddley, RN - study4u@vcu.edu
NCT06981195
Inclusion Criteria:
• Be 18 + years-of-age
• Meet current DSM-5 criteria for opioid use disorder (OUD) with at least moderate severity
• Receiving outpatient treatment for OUD with sublingual buprenorphine film/tablets ranging 8mg to 24mg or with extended-release injectable buprenorphine
• Stabilized on current buprenorphine dosage for at least 4 weeks without intention for dose change within next 3 months.
• Screening urine toxicology positive for buprenorphine and an appropriate norbuprenorphine level as determined by a study clinician
• A screening urine toxicology negative for non-prescribed substances (except cannabinoids) with a negative breath (or oral fluid) alcohol screen
• Screen positive for chronic insomnia on the Insomnia Symptom Questionnaire (ISQ)
• Have an Insomnia Severity Index score at screening and baseline of 13 or higher
• Have no clinically significant medical or psychiatric disorder or condition, based on physical exam and medical history performed by study clinician, that in the judgement of the investigator would prevent participation or heighten safety risks
• Understand the study procedures and provide written informed consent in English language
• Access to necessary resources for completing virtual surveys and monitoring (i.e., computer or smartphone, internet or cell service)
Exclusion Criteria:
• Current diagnosis of sleep-related breathing disorder, narcolepsy, somnambulism, or sleep paralysis
• A positive screen for sleep apnea by the following: Sleep Disorders Screening Battery (STOP-BAG \>5) OR home sleep apnea test using WatchPAT with Apnea Hypopnea Index (AHI) with 3% drop in oxygen saturation \> 10 OR \>50% of respiratory events being central if AHI is between 5-10 OR Oxygen Desaturation \< 88% for \> 10 minutes, OR oxygen desaturation index (ODI) using 3% drop in oxygen saturation \> 10
• Currently receiving treatment for insomnia (behavioral or pharmacologic)
• Currently taking a medication to treat a sleep-related condition (e.g., zolpidem) or unable to discontinue over-the-counter drug or supplement used to treat sleep-related condition
• Currently taking benzodiazepines or other CNS active medications that may increase risk to the participant, per PI discretion (e.g., opioids other than buprenorphine, antipsychotics)
• Current DSM-5 diagnosis (any severity) of alcohol or drug use disorder (e.g., benzodiazepine, stimulant) with non-prescribed substance use within last 3 months; nicotine use disorder is not considered exclusionary
• Cannabis use \> 3 days/week
• Uncontrolled serious psychiatric disorder that would make study participation unsafe (such as Bipolar I Disorder, ADHD, Schizophrenia, schizoaffective disorders, major depressive disorder with psychotic features, or a neurological disorder).
• Uncontrolled neurological, cardiovascular, or pulmonary medical condition such as seizure disorder, recent myocardial infarction, stroke, hospitalization for chronic obstructive pulmonary disease
• Baseline ECG with clinically significant abnormal conduction or with QTc of greater than 450ms
• Significant current suicidal or homicidal ideation (C-SSRS "yes" answers on questions 4 or 5) or a history of suicide attempt within the past 6 months
• Any of the following lab abnormalities: ALT/AST 2 or more times the upper limit of normal, Total bilirubin 2 or more times the upper limit of normal, Creatinine 1.5 or more times the upper limit of normal
• Pregnant or breastfeeding; Females who are having sex that includes penile penetration must be non-pregnant, non-lactating, and either be of non-childbearing potential (e.g., sterilized via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal) or of childbearing potential, and agree to use an acceptable form of contraception (e.g., IUD, hormonal implant, hormonal patch/ring/pill, condoms (male or female), etc.)
• Currently taking prescription or over-the counter drugs or dietary supplements known to significantly inhibit CYP3A4 (such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir); or CYP3A4 inducers (such as phenobarbital, phenytoin, rifampicin, St. John's Wort, and glucocorticoids)
• Currently taking lemborexant or any previous medically adverse reaction to lemborexant or other dual orexin receptor antagonists
• Currently incarcerated or pending incarceration
DRUG: Placebo, DRUG: Lemborexant 10 MG
Opioid Use Disorder, Opioid Use, Insomnia, Orexin Antagonist
buprenorphine, lemborexant
TIDES 2.0: Prevalence and Longitudinal Course of Depression, Anxiety, and Behavior Problems in Children With Cystic Fibrosis Under 12 Years of Age (TIDES 2)
Beth A Smith, MD - balucas@buffalo.edu
NCT07048574
Inclusion Criteria:
• Child with a diagnosis of Cystic fibrosis (CF) actively followed by the CF care team at a participating site
• Child is age 18 months thru 11 years
• English and/or Spanish speaking
• Parent/legal guardian willing and able to give informed consent, and for minor participants ages 7 thru 11 years able to give assent.
Exclusion Criteria:
* Unable or unwilling to participate in study procedures, or at Site PI discretion. Cystic Fibrosis (CF)
Cystic Fibrosis, Children, Mental health screening, Depression, Anxiety, CFTR modulators, Neuropsychiatric adverse events
Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to Radiation Therapy Compared to the Usual Chemotherapy Treatment During Radiation Therapy for Bladder Cancer, PARRC Trial
ctrrecruit@vcu.edu
NCT06770582
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of T1 high-grade non-muscle invasive urothelial carcinoma of the bladder without radiographic evidence of regional nodal disease or metastatic disease (N0, M0) on CT, MRI, or positron emission tomography (PET)/CT scan who would otherwise be treated with cystectomy off-trial. Patients should have cystectomy recommended disease but do not need to be medically operable for a cystectomy to be eligible for the trial.
* NOTE: Patients with nodal disease ≥ 1 cm on short-axis or with suspicious nodes that are PET-avid of any size are not eligible
* High grade T1 disease history that must meet at least ONE of the three criteria below:
* Histologically confirmed recurrence with high-grade T1 urothelial carcinoma (+/- focal carcinoma in situ \[CIS\]) in the bladder following initial transurethral resection of bladder tumor (TURBT) and at least one induction course of intravesical therapy. Adequate induction course is defined as ≥ 5 doses of intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy when BCG is not available.
* T1 with pathologic high-risk features (lymphovascular invasion \[LVI\] or variant histology of micropapillary, sarcomatoid, or plasmacytoid features) post initial TURBT. (No prior intravesical therapy required)
* Persistent high-grade T1 urothelial carcinoma at repeat TURBT (+/- focal CIS) in the bladder. (No prior intravesical therapy required)
* Restaging TURBT must be performed and must meet ALL of the following criteria below:
* If there is absence of muscularis propria in the initial TURBT, there must be uninvolved muscularis propria in the restaging TURBT.
* All grossly visible papillary tumors must be removed
* Note: If the restaging TURBT is performed outside of the enrolling institution, an office cystoscopy should be performed by a Urologist who will be following the patient as part of the clinical trial
* No pure squamous cell carcinoma or adenocarcinoma of the bladder
* No neuroendocrine (small or large cell) features
* No diffuse carcinoma in situ determined on cystoscopy and biopsy (i.e. extensive carcinoma in situ that is not just tumor-associated CIS in the opinion of the site investigator)
* No prostatic urethral involvement
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 9 g/dl is acceptable)
* Adequate renal function defined as creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula, ≤ 1.5 × upper limit of normal (ULN) or creatinine levels \> 1.5 × institutional ULN
* Total bilirubin ≤ institutional upper limit of normal (ULN) (Not applicable to patients with known Gilbert's syndrome)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x institutional ULN
* All adverse events of their most recent therapy/intervention must have resolved to \< grade 3 or returned to baseline prior to registration
* No history of pelvic radiation therapy
* No prior systemic chemotherapy or immunotherapy for urothelial carcinoma. Prior treatment with local intravesical therapy including BCG or chemotherapy is allowed
* No prior treatment with anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4 antibody or any other antibody or drug targeting T-cell co-stimulation
* No live vaccine administered within 30 days of registration. All non live vaccines (including the coronavirus disease \[COVID\] vaccine) are allowed at any time during the study. Timing should minimize confusion with drug-related toxicities where possible
* Patients must have recovered from acute cardiac illness
* New York Heart Association Functional Classification II or better (New York Heart Association \[NYHA\] Functional Classification III/IV are not eligible) (Note: 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.)
* No active infection requiring IV antibiotics
* No active autoimmune disease that required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* No history of idiopathic pulmonary fibrosis, organizing pneumonia, (non-infectious) pneumonitis that required steroids or current pneumonitis
* No history of allogeneic bone marrow transplant or prior solid organ transplant
* No active tuberculosis
* No evidence of hydronephrosis
* No history of upper tract urothelial carcinoma within 24 months of registration
* No patients with a prior diagnosis of prostate cancer who have not received definitive treatment for their prostate cancer (e.g. on active surveillance)
* 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 glucocorticoids except physiologic doses are allowed. The use of doses of corticosteroids (defined as 10 mg prednisone or equivalent) is acceptable
* No history of allergic reaction to the drug excipients PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Fluorouracil, DRUG: Gemcitabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mitomycin, BIOLOGICAL: Pembrolizumab, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy
Non-Muscle Invasive Bladder Urothelial Carcinoma, Recurrent Non-Muscle Invasive Bladder Urothelial Carcinoma, Stage I Bladder Cancer AJCC v8
PAS 1ml Magtrace® for Sentinel Lymph Node Biopsy in Breast Cancer Patients (MAGProm)
Vicky Crawford - vcrawford@endomag.com
NCT06610539
Inclusion Criteria:
* Patient is willing and able to give informed consent for participation in the study
* Patient is aged 18 years or older at the time of consent
* Patients undergoing planned breast conserving surgery (for example, lumpectomy or partial mastectomy) and SLNB with Magtrace
Exclusion Criteria:
* The patient is pregnant or lactating
* The patient has had prior breast radiation to the ipsilateral breast
* The patient has clinical or radiological evidence of metastatic cancer including palpably abnormal or enlarged lymph nodes
* The patient has recevied a Feraheme (ferumoxytol) injection within the past 6 months
* The patient has intolerance or hypersensitivity to iron or dextran compounds or to Magtrace
* The patient has iron overload disease
* The patient has discoloration on the breast (such as tattoo, birthmark, tanning, rash etc.), that in the Investigator's opinion, could impact the clinical trial results, specifically the assessment of any skin discoloration, or plans to have a tattoo on the breast post-operatively. Breast Cancer
Magtrace, Sentinel Lymph Node Biopsy
A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
ctrrecruit@vcu.edu
NCT06124157
Inclusion Criteria:
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria:
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Imatinib, DRUG: Leucovorin, DRUG: Mercaptopurine, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Pegaspargase, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine
B Acute Lymphoblastic Leukemia