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A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
ALL
2 Years to 21 Years old
PHASE3
NCT04166409
STU-2020-0013
Inclusion Criteria:
* Patients must be \>= 2 years and =\< 21 years at the time of enrollment
* Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
* Patients must have non-neurofibromatosis type 1 (non-NF1) low-grade glioma (LGG) without a BRAFV600E mutation as confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1 (NCT02402244) Childhood Cancer Data Initiative (CCDI)-MCI, or accepted Clinical Laboratory Improvement Act (CLIA)-certified test and that has not been treated with any modality besides surgery. Note: Patients may be newly-diagnosed OR previously diagnosed, and there is no required time frame between biopsy/surgery and treatment initiation.
* Patients with residual tumor after resection or progressive tumor after initial diagnosis (with or without surgery) who have not received treatment (chemotherapy and/or radiation) are eligible
* Patients must have two-dimensional measurable tumor \>= 1 cm\^2 to be eligible
* Patients with ependymoma are not eligible
* Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade I and II) by 5th edition WHO classification of central nervous system (CNS) tumors with the exception of subependymal giant cell astrocytoma
* Patients with metastatic disease or multiple independent primary LGG are eligible
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (performed within 7 days prior to enrollment):
* Age: Maximum Serum Creatinine (mg/dL)
* 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female)
* 6 to \< 10 years: 1 mg/dL (male); 1 mg/dL (female)
* 10 to \< 13 years: 1.2 mg/dL (male); 1.2 mg/dL (female)
* 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
* \>= 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (performed within 7 days prior to enrollment) (children with a diagnosis of Gilbert's syndrome will be allowed on study regardless of their total and indirect \[unconjugated\] bilirubin levels as long as their direct \[conjugated\] bilirubin is \< 3.1 mg/dL)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (performed within 7 days prior to enrollment)
* Left ventricular ejection fraction (LVEF) \>= 53% (or institutional normal; if the LVEF result is given as a range of values, then the upper value of the range will be used) by echocardiogram (performed within 4 weeks prior to enrollment)
* Corrected QT (QTc) interval =\< 450 msec by electrocardiography (EKG) (performed within 4 weeks prior to enrollment)
* Absolute neutrophil count \>= 1,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Platelets \>= 100,000/uL (unsupported) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8 g/dL (may be supported) (performed within 7 days prior to enrollment)
* Patients with a known seizure disorder must be stable and must not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
* Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and sex at the time of enrollment (with or without the use of anti-hypertensive medications)
* Patients \>= 18 years of age must have a blood pressure =\< 130/80 mmHg at the time of enrollment (with or without the use of anti-hypertensive medications)
* Note for patients of all ages: Adequate blood pressure can be achieved using medication for the treatment of hypertension
* All patients must have ophthalmology toxicity assessments performed within 8 weeks prior to enrollment
* For all patients, an MRI of the brain (with orbital cuts for optic pathway tumors) and/or spine (depending on the site(s) of primary disease) with and without contrast must be performed within 8 weeks prior to enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have the ability to swallow whole capsules
* 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
* All patients have signed an appropriate consent form and Health Insurance Portability and Accountability Act (HIPAA) authorization form (if applicable)
* All patients have been consented and enrolled on APEC14B1 (NCT02402244) Part A for Pre-Enrollment Eligibility Screening for ACNS1833
Exclusion Criteria:
* Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant. Prior surgical intervention (with the exclusion of laser interstitial thermal therapy \[LITT\]) is permitted
* Patients with a concurrent malignancy or history of treatment (other than surgery) for another tumor within the last year are ineligible
* Patients with diffuse intrinsic pontine tumors as seen on MRI (\> 2/3 of pons involvement on imaging) are not eligible even if biopsy reveals grade I/II histology
* Patients may not be receiving any other investigational agents
* Patients with any serious medical or psychiatric illness/condition, including substance use disorders or ophthalmological conditions, likely in the judgment of the investigator to interfere or limit compliance with study requirements/treatment
* Patients who, in the opinion of the investigator, are not able to comply with the study procedures are not eligible
* Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are not eligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 1 week after stopping study therapy are not eligible.
* Note: Women study participants of child-bearing potential must use acceptable contraception during the study and for 1 week (7 days) after the last dose of selumetinib. Men study participants with sexual partners who are pregnant or who are of child-bearing potential must use acceptable contraception during the study and for 1 week (7 days) after the last dose of study agent. Acceptable contraception includes implants, injectables, or oral contraceptives (all combined with barrier methods), some intrauterine devices (IUDs), vasectomy or abstinence
* Known genetic disorder that increases risk for coronary artery disease. Note: The presence of dyslipidemia in a family with a history of myocardial infarction is not in itself an exclusion unless there is a known genetic disorder documented
* Symptomatic heart failure
* New York Health Association (NYHA) class II-IV prior or current cardiomyopathy
* Severe valvular heart disease
* History of atrial fibrillation
* Current or past history of central serous retinopathy
* Current or past history of retinal vein occlusion or retinal detachment
* Patients with uncontrolled glaucoma
* If checking pressure is clinically indicated, patients with intraocular pressure (IOP) \> 22 mmHg or ULN adjusted by age are not eligible
* Supplementation with vitamin E greater than 100% of the daily recommended dose. Any multivitamin containing vitamin E must be stopped prior to study enrollment even if less than 100% of the daily recommended dosing for vitamin E
* Surgery within 2 weeks prior to enrollment, with the exception of surgical biopsy, placement of a vascular access device or cerebral spinal fluid (CSF) diverting procedure such as endoscopic third ventriculostomy (ETV) and ventriculoperitoneal (VP) shunt.
* Note: Patients must have healed from any prior surgery
* Patients who have an uncontrolled infection are not eligible PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, OTHER: Questionnaire Administration, DRUG: Selumetinib Sulfate, DRUG: Vincristine Sulfate
Low Grade Astrocytoma, Low Grade Glioma, Metastatic Low Grade Astrocytoma, Metastatic Low Grade Glioma, WHO Grade 1 Glioma, WHO Grade 2 Glioma, Brain and Nervous System
Children’s Health
Testing the Addition of the Drug Apalutamide to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer, INNOVATE Trial (INNOVATE)
This phase III trial studies whether adding apalutamide to the usual treatment improves outcome in patients with lymph node positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or reduce the growth of prostate cancer cell growth by blocking the attachment of androgen to its receptors on cancer cells, a mechanism similar to stopping the entrance of a key into its lock. Adding apalutamide to the usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading and extend time without disease spreading compared to the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aurelie Garant
MALE
18 Years and over
PHASE3
NCT04134260
STU-2020-0570
Inclusion Criteria:
* Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted
* Any T-stage is eligible (American Joint Committee on Cancer \[AJCC\] 8th edition \[ed\])
* Appropriate stage for study entry based on fluciclovine F-18 PET scan (FACBC, Axumin) F-18 prostate-specific membrane antigen (PSMA) PET (PyLarify) scan, Gallium-68 PSMA PET scan, flotufolastat F-18 PSMA PET scan (Posluma), or C-11 or F-18 Choline PET within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease. For patients with PSA \< 0.20 ng/mL at time of registration, PET scan is recommended but not required
* Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen or nodal disease on imaging at time of recurrence (including external iliacs, internal iliacs, and/or obturator nodes); peri-prostatic and peri-rectal nodes can also be considered regional lymphadenopathy and are allowed
* History/physical examination within 90 days prior to registration
* Age \>= 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration
* Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA \> 0 ng/mL at least 30 days after prostatectomy
* Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =\< 180 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =\< 180 days and stopped prior to registration)
* Hemoglobin \>= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)
* Platelet count \>= 100,000 x 10\^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)
* Serum potassium \>= 3.5 mmol/L within 90 days prior to registration
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =\< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (within 90 days prior to registration)
* Serum albumin \>= 3.0 g/dL (within 90 days prior to registration)
* Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration
* The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count \>= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol
* 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 within 30 days 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. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ) who has no evidence of disease for \< 3 years must contact the principal investigator, Ronald Chen, Doctor of Medicine (MD)
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
Exclusion Criteria:
* Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, \[FACBC, Axumin\], F-18 PSMA PET \[Pylarify\], flotufolastat F-18 PSMA PET scan \[Posluma\], Gallium-68 PSMA PET scan or C-11 choline PET)
* Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
* Androgen deprivation therapy (ADT) prior to radical prostatectomy
* Prior treatment with androgen receptor signaling inhibitor (including but not exclusive to a growing list of: abiraterone acetate, enzalutamide, apalutamide, darolutamide), unless started =\< 180 days and stopped prior to registration, which is allowed
* Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible
* History of any of the following:
* Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system \[CNS\] or meningeal disease which may require treatment with surgery or radiation therapy)
* Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 12 months prior to registration
* New York Heart Association functional classification III/IV (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.)
* History of any condition that in the opinion of the investigator, would preclude participation in this study
* Current evidence of any of the following:
* Known gastrointestinal disorder affecting absorption of oral medications
* Active uncontrolled infection
* Presence of uncontrolled hypertension (persistent systolic blood pressure \[BP\] \>= 160 mmHg or diastolic BP \>= 100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment
* Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily
* Baseline moderate and severe hepatic impairment (Child-Pugh Class B \& C)
* Inability to swallow oral pills
* Any current condition that in the opinion of the investigator, would preclude participation in this study
* Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study
* Patients with inflammatory bowel disease DRUG: Apalutamide, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Hormone Therapy, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy
Prostate Adenocarcinoma, Stage I Prostate Cancer AJCC v8, Stage II Prostate Cancer AJCC v8, Stage III Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Prostate
Prostate Cancer, Apalutamide, Abiraterone Acetate
UT Southwestern; Parkland Health & Hospital System
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
up to 25 Years old
PHASE1
NCT04094610
STU-2019-1268
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma, Primary CNS Tumors, Breast - Female, Breast - Male, Colon, Kidney, Lung/Thoracic, Rectum, Soft Tissue, Thyroid, Urinary Bladder
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
Cobimetinib in Refractory Langerhans Cell Histiocytosis (LCH), and Other Histiocytic Disorders (NACHO-COBI)
This is a research study of a drug called cobimetinib in children and adults diagnosed with Langerhans cell histiocytosis (LCH), and other histiocytic disorders that has returned or does not respond to treatment. Cobimetinib blocks activation of a protein called Mitogen-activated protein kinase (MEK) that is part of incorrect growth signals in histiocytosis cells. Four different groups of patients will be enrolled.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Erin Butler
All
Not specified
Phase 2
NCT04079179
STU-2021-0830
INCLUSION CRITERIA:
Age at study entry
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
• For Group 1: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 2: Participant may be at least 6 months of age at the time of enrollment
• For Group 3: Participant must be at least 6 months of age and less than 21 years of age at the time of enrollment
• For Group 4: Participant must be 21 years of age or older at the time of enrollment
• Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet which may be taken by mouth or other enteral route such as nasogastric or gastric tube.
• Biopsy proven LCH -AND
• Failure of at least front-line therapy for LCH with evaluable disease. -OR
• Diagnosis of LCH-associated neurodegenerative disease with radiologic or clinical progression within the past 3 months. -OR
• Biopsy proven JXG, ECD, RDD, histiocytic sarcoma, or other histiocytic lesion (newly diagnosed or relapsed/refractory disease) with evaluable active disease. Performance Level: -Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Adequate Hematologic Function Defined as:
• ANC ≥ 0.75 x 10^9/L (unsupported/without growth factor stimulant)
• Platelet count ≥ 75 x 10^9/L (unsupported/without transfusion within the past 7 days).
• Patients with marrow disease must have platelet count of >/= 75 x 10^9/L (transfusion support allowed) and must not be refractory to platelet transfusions.
• Hemoglobin ≥ 8 g/dL (unsupported/without transfusion within the past 7 days)
• Patients with marrow disease must have hemoglobin ≥ 8 g/dL (transfusion support allowed). Adequate Renal Function Defined as:
• Calculated creatinine clearance (or radioisotope GFR) ≥ 70 mL/min/1.73m^2 or serum creatinine based on age/gender as follows: Maximum Serum Creatinine (mg/dL) Age 2 to < 6 years: Male 0.8 mg/d, Female 0.8; 6 to < 10 years: Male 1 mg/dL,Female 1; 10 to < 13 years: Male 1.2 mg/dL; Female 1.2; 13 to < 16 years: Male 1.5 mg/dL ; Female 1.4; ≥ 16 years: Male 1.7 mg/dL; Female 1.4; Adequate Liver Function Defined as:
• Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
• AST and ALT ≤ 3x ULN (≤ 5 x ULN for participants with liver involvement)
• Serum albumin ≥ 2 g/dL. For patients with liver disease caused by histiocytic disorder: • Patients may be enrolled with abnormal bilirubin, AST, ALT and albumin with documentation of histiocytic liver disease. Adequate Cardiac Function Defined as:
• Fractional shortening (FS) of ≥ 30% or ejection fraction of ≥ 50% by echocardiogram at baseline, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to enrollment. Depending on institutional standard, either FS or LVEF is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above Pregnancy/Birth Control
• Female patients of childbearing potential require a negative urine or serum pregnancy test for eligibility and again at database registration, if more than 2 weeks has elapsed.
• Female patients of childbearing potential must agree to follow the contraceptive requirements using two forms of effective contraceptive methods for the duration of the study treatment. Male patients with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) must agree to use two forms of effective methods of contraception (one of which must be a barrier method) during the treatment period and for at least 3 months after the last dose of the study drug to avoid pregnancy and/or potential adverse effects on a developing embryo. Agreement to true abstinence (not periodic abstinence or withdrawal method) is an acceptable method of birth control. EXCLUSION CRITERIA:
• Prior and Concomitant Use of Drugs with CYP3A4 inducing/inhibiting activity: Patient taking strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment, including but not limited to the following: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's wort.
• Prior Therapy Restrictions Completion of previous chemotherapy, immunotherapy, radiotherapy, or targeted therapy for LCH (or other histiocytic disorder) at least 28 days (except where specified below) prior to study enrollment, with resolution of all associated toxicity to ≤ Grade 1 prior to study enrollment (exception for alopecia and ototoxicity which do not need to be resolved ≤ Grade 1). Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the laboratory eligibility criteria are met, the patient is considered to have recovered adequately.
• Radiation therapy within the 28 days prior to enrollment.
• Any prior treatment with Cobimetinib.
• Treatment with a long-acting hematopoietic growth factor within 14 days prior to initiation of study drug or a short-acting hematopoietic growth factor within 7 days prior to enrollment.
• Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives), immunotherapy, biologic therapy, investigational therapy, or herbal cancer therapy within 28 days or < 5 half-lives, whichever is longer, prior to study enrollment.
• Treatment with high-dose chemotherapy and stem-cell rescue (autologous stem cell transplant) or allogeneic stem cell transplant within 90 days prior to enrollment. Anti-GVHD agents post-transplant: Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
• For patients with brain tumors (intracranial masses), use of anticoagulants within 7 days prior to enrollment.
• Corticosteroid therapy <0.5 mg/kg/day averaged during the month prior to study enrollment is permissible but must be discontinued fourteen (14) days prior to enrollment. Patients with documented brain lesions receiving corticosteroids for management of cerebral edema must be on a stable dose for fourteen (14) days prior to enrollment.
• Patient has received treatment with investigational therapy within 4 weeks prior to initiation of study drug.
• Patients taking anticoagulants or have a pre-existing bleeding disorder unrelated to histiocytic disease.
• Exclusions for other illness
• Other active malignancy or history of secondary malignancy.
• Refractory nausea and vomiting, malabsorption, external biliary shunt
• Infection: Patients who have a known active infection (excluding documented fungal infection of the nail beds) within 28 days prior to enrollment that has not completely resolved.
• Major surgical procedure or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days prior to study enrollment (provided that the wound has healed).
• History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease.
• History of pneumonitis.
• Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion are not eligible. Specifically, patients with a history of retinal vein occlusion (RVO), retinal detachment, retinal pathology on ophthalmologic exam, retinopathy of prematurity, central serous chorioretinopathy (CSSCR), neovascular retinopathy, intraocular pressure > 21 mmHg, and predisposing factors to RVO (e.g., uncontrolled hypertension, diabetes, or hyperlipidemia, coagulopathy) will be excluded. Patients with longstanding and stable ophthalmologic findings secondary to existing conditions are eligible with appropriate written documentation and approval from Study Chair.
• History of solid organ transplantation: Patients who have received a prior solid organ transplantation are not eligible.
• Any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that in the opinion of the investigator contraindicates use of an investigational drug or places the patient at unacceptable risk from treatment complications.
• History of clinically significant cardiac dysfunction, including the following:
• Clinically significant cardiac arrhythmias including brady-arrhythmias and/or patients who require anti-arrhythmic therapy (with the exception of beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
• Unstable arrhythmia
• Unstable angina, or new-onset angina within 3 months prior to initiation of study treatment
• Symptomatic congestive heart failure, defined as New York Heart Association Class II or higher
• Myocardial infarction within 3 months prior to initiation of study treatment
• Known chronic human immunodeficiency virus (HIV).
• History of Grade ≥ 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of enrollment.
• Female patients who are pregnant or lactating. Pregnant or lactating women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities.
Drug: Cobimetinib
Langerhan's Cell Histiocytosis, Juvenile Xanthogranuloma, Erdheim-Chester Disease, Rosai Dorfman Disease, Neuro-Degenerative Disease, Histiocytic Sarcoma, Histiocytic Disorders, Malignant, Bones and Joints, Brain and Nervous System, Liver, Lung/Thoracic, Other Hematopoietic
Cobimetinib, Langerhans Cell Histiocytosis (LCH)
Children’s Health
DBS of the SCC for the Treatment of Medically Refractory CLBP
The purpose of this study is to evaluate the feasibility and preliminary efficacy of deep brain stimulation of the subgenual cingulate cortex for the treatment of chronic medically-refractory low back pain using a randomized double-blind crossover design.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Andrew.Mills@UTSouthwestern.edu
Nader Pouratian
ALL
40 Years to 75 Years old
NA
NCT04085406
STU-2023-0540
Inclusion Criteria:
* Pain secondary to failed back surgery syndrome (FBSS) as defined by persistent low back pain despite prior surgical interventions.
* Self-reported average back pain intensity of greater than 8 out of 10 on the Visual Analog Scale (VAS) documented over greater than 2 years.
* Failure to achieve at least 50% pain relief from a trial of spinal cord stimulation (SCS) or less than 50% pain relief after 3 months of SCS therapy or patient refuses/rejects SCS trial
* Failure to achieve at least 50% pain relief in response to at least 4 weeks of physical therapy.
* Failure to achieve at least 50% pain relief in response to at least 2 percutaneous spinal pain procedures.
* Failure to achieve at least 50% pain relief in response to 3 months of opioid therapy (at least 20 MEQ/day) or inability to increase or tolerate opioid therapy due to dose-limiting side effects).
* Failure to achieve at least 50% pain relief in response to a 3-month trial of at least one other class of pain medication in addition to opioid therapy or inability to tolerate increasing doses of non-opioid pain medications due to dose-limiting side effects.
* Lack of a surgically correctible etiology for the pain as determined by 2 independent neurosurgeons
* Age greater than 40 years of age.
* Ability to give informed consent in accordance with institutional policies and participate in the 1.5-year follow-up, involving assessments and stimulator adjustments.
* Willingness to share unexpected neurological or psychiatric symptoms with study clinicians.
Exclusion Criteria:
* Significant neurocognitive impairment (MoCA \< 26).
* Age \> 75 years.
* History of implant-related infection.
* History of bleeding disorder or immune-compromise.
* Psychiatric comorbidity other than depression or generalized anxiety disorder, as determined by MINI International Neuropsychiatric Interview.
* Patients with neurological diagnoses that may reduce the response to or increase the risk of DBS including neurodegenerative conditions, severe movement disorders, demyelinating disorders, syringomyelia, epilepsy or history of seizures, history of CNS tumors (spinal and/or cranial), history of serious head injury with loss of consciousness, history of stroke, surgically reversible peripheral pain syndromes including surgically correctable radiculopathy, and severe peripheral neuropathy.
* Patients who have undergone spine surgery within the previous 3 months.
* Major medical co-morbidities increasing the risk of surgery including uncontrolled hypertension, severe diabetes, major organ system failure, history of hemorrhagic stroke, need for chronic anticoagulation, active infection, immunocompromised state or malignancy with \< 5 years life expectancy.
* Individuals with a currently implanted SCS device.
* Individuals with a life expectancy less than 1 year due to any cause.
* Individuals involved in an injury claim under current litigation.
* Individuals with a pending or approved worker's compensation claim.
* Patient living greater than 100 miles from UCLA.
* Suicide attempt in the last two years and/or presence of a suicide plan (an answer of Yes to Question C4 in Section C- Suicidality of MINI International Neuropsychiatric Interview).
* Alcohol or illicit substance use disorder (other than nicotine) within the last 6 months, unstable remission of substance abuse, or chart evidence that co-morbid substance use disorder could account for lack of treatment response.
* Uncontrolled medical condition including cardiovascular problems and diabetes.
* Pregnant or planning to become pregnant.
* Use of warfarin or other blood thinners.
* Significant structural abnormality on preoperative brain MRI.
* Contraindications to MRIs or the need for recurrent body MRIs.
* Presence of cardiac pacemakers/defibrillators, implanted medication pumps, intra-cardiac lines, any intracranial implants (e.g., aneurysm clip, shunt, cochlear implant, electrodes) or other implanted stimulators.
* History of prior cranial neurosurgery.
* Patients unable to discontinue any existing therapeutic diathermy.
* Individuals who are concomitantly participating in another clinical study. DEVICE: Deep Brain Stimulation of the Subgenus Cingulate Cortex
Chronic Low-back Pain, Bones and Joints
UT Southwestern
Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (BEAT-MS)
This is a multi-center prospective rater-masked (blinded) randomized controlled trial of 156 participants, comparing the treatment strategy of Autologous Hematopoietic Stem Cell Transplantation (AHSCT) to the treatment strategy of Best Available Therapy (BAT) for treatment-resistant relapsing multiple sclerosis (MS). Participants will be randomized at a 1 to 1 (1:1) ratio. All participants will be followed for 72 months after randomization (Day 0, Visit 0).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Manuel.Huichapa@UTSouthwestern.edu
Benjamin Greenberg
ALL
18 Years to 55 Years old
PHASE3
NCT04047628
STU-2020-0855
Inclusion Criteria:
• Age 18 to 55 years, inclusive, at the time of the screening Visit -2.
• Diagnosis of MS according to the 2017 McDonald Criteria139.
• EDSS ≤ 6.0 at the time of randomization (Day 0).
• T2 abnormalities on brain MRI that fulfill the 2017 McDonald MRI criteria for dissemination in space139. A detailed MRI report or MRI images must be available for review by the site neurology investigator.
• Highly active treatment-resistant relapsing MS, defined as ≥ 2 episodes of disease activity in the 36 months prior to the screening visit (Visit -2). The two disease activity episodes will be a clinical MS relapse or MRI evidence of MS disease activity and must meet all the criteria described below:
• At least one episode of disease activity must occur following ≥ 1 month of treatment with one of the following: (i) an oral DMT approved by the FDA for the treatment of relapsing MS, or (ii) a monoclonal antibody approved by the FDA for the treatment of relapsing MS, or (iii) rituximab. Qualifying DMTs include: dimethyl fumarate, diroximel fumarate, monomethyl fumarate, teriflunomide, cladribine, daclizumab, ponesimod, siponimod, ozanimod, fingolimod, rituximab, ocrelizumab, natalizumab, alemtuzumab, ublituximab, and ofatumumab, and
• At least one episode of disease activity must have occurred within the 12 months prior to the screening visit (Visit -2), and
• At least one episode of disease activity must be a clinical MS relapse (see item c.i. below). The other episode(s) must occur at least one month before or after the onset of the clinical MS relapse, and must be either another clinical MS relapse or MRI evidence of disease activity (see item c.ii. below): i. Clinical MS relapse must be confirmed by a neurologist's assessment and documented contemporaneously in the medical record. If the clinical MS relapse is not documented in the medical record, it must be approved by the study adjudication committee (see Section 3.5), and ii. MRI evidence of disease activity must include ≥ 1 unique active lesion on one or more brain or spinal cord MRIs. Detailed MRI reports or MRI images must be available for review by the site neurology investigator. A unique active lesion is defined as either of the following: 1\. A gadolinium-enhancing lesion, or 2. A new non-enhancing T2 lesion compared to a reference scan obtained not more than 36 months prior to the screening visit (Visit -2). 6\. Candidacy for treatment with at least one of the following high efficacy BAT DMTs: cladribine, natalizumab, alemtuzumab, ocrelizumab, ofatumumab, ublituximab and rituximab. Candidacy for treatment for each BAT DMT is defined as meeting all of the following:
• No prior disease activity episode, as defined in Inclusion Criterion #5, with the candidate BAT DMT, and
• No contraindication to the candidate BAT DMT, and
• No treatment with the candidate BAT DMT in the 12 months prior to screening. 7\. Completion of COVID-19 vaccination series, according to the current Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommendations, ≥ 14 days prior to randomization (Day 0). 8\. Positive for VZV antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least 4 weeks prior to randomization (Day 0). 9\. Insurance approval for MS treatment with at least one candidate BAT DMT (see Inclusion Criterion #6). 10\. Ability to comply with study procedures and provide informed consent, in the opinion of the investigator. 11\. Females of childbearing potential (defined in Section 5.4.3.1) and males with female partners of childbearing potential are required to adhere to the contraception provisions of Section 5.4.3.1. 12\. For participants who use medicinal or recreational marijuana, willingness to substitute MARINOL® if randomized to AHSCT (Section 5.4.2.6).
Exclusion Criteria:
• Diagnosis of primary progressive MS according to the 2017 McDonald criteria.
• History of neuromyelitis optica spectrum disorder or MOG antibody disease.
• Prior treatment with an investigational agent within 3 months or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of COVID-19 are not considered investigational.
• Either of the following within one month prior to randomization (Day 0):
• Onset of acute MS relapse, or
• Treatment with intravenous methylprednisolone 1000 mg/day for 3 days or equivalent.
• Initiation of any BAT DMT (see Section 5.2.1) between Visit -2 and randomization (Day 0).
• Brain MRI or cerebrospinal fluid (CSF) examination indicating a diagnosis of progressive multifocal leukoencephalopathy (PML).
• History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
• Presence of unexplained cytopenia, polycythemia, thrombocythemia or leukocytosis.
• History of sickle cell anemia or other hemoglobinopathy.
• Evidence of past or current hepatitis B or hepatitis C infection, including treated hepatitis B or hepatitis C. Hepatitis B surface antibody following hepatitis B immunization is not considered to be evidence of past infection.
• Presence or history of mild to severe cirrhosis.
• Hepatic disease with the presence of either of the following:
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN) or total bilirubin ≥ 3.0 times the ULN in the presence of Gilbert's syndrome, or
• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 2.0 times the ULN.
• Positive COVID-19 PCR test, or alternative nucleic acid amplification test (NAAT) per institutional standards, within 14 days prior to randomization (Day 0).
• Evidence of HIV infection.
• Positive QuantiFERON - TB Gold,TB Gold Plus, or T-SPOT®.TB test results. PPD tuberculin test may be substituted for QuantiFERON - TB Gold, TB Gold Plus, or T-SPOT®.TB test.
• Active viral, bacterial, endoparasitic, or opportunistic infections.
• Active invasive fungal infection.
• Hospitalization for treatment of infections or parenteral (IV or IM) antibacterials, antivirals, antifungals, or antiparasitic agents within the 30 days prior to randomization (Day 0) unless clearance is obtained from an Infectious Disease specialist.
• Receipt of live or live-attenuated vaccines within 6 weeks of randomization (Day 0).
• Presence or history of clinically significant cardiac disease including: a. Arrhythmia requiring treatment with any antiarrhythmia therapy, with the exception of low dose beta blocker for intermittent premature ventricular contractions. b. Coronary artery disease with a documented diagnosis of either: i. Chronic exertional angina, or ii. Signs or symptoms of congestive heart failure. c. Evidence of heart valve disease, including any of the following: i. Moderate to severe valve stenosis or insufficiency, or ii. Symptomatic mitral valve prolapse, or iii. Presence of prosthetic mitral or aortic valve.
• Left ventricular ejection fraction (LVEF) \< 50%.
• Impaired renal function defined as eGFR \< 60 mL/min/1.73 m2, according to the CKD-EPI formula144.
• Forced expiratory volume in one second (FEV1) \< 70% predicted (no bronchodilator).
• Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for Hgb) \< 70% predicted.
• Poorly controlled diabetes mellitus, defined as HbA1c \> 8%.
• History of malignancy, except adequately treated localized basal cell or squamous skin cancer, or carcinoma in situ of the cervix. Malignancies for which the participant is judged to be cured will be considered on an individual basis by the study adjudication committee (see Section 3.5).
• Presence or history of any moderate to severe rheumatologic autoimmune disease requiring treatment, including but not limited to the following: systemic lupus erythematous, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, polymyositis, dermatomyositis, mixed connective tissue disease, polymyalgia rheumatica, polychondritis, sarcoidosis, vasculitis syndromes, or unspecified collagen vascular disease.
• Presence of active peptic ulcer disease, defined as endoscopic or radiologic diagnosis of gastric or duodenal ulcer.
• Prior history of AHSCT.
• Prior history of solid organ transplantation.
• Positive pregnancy test or breastfeeding.
• Failure to willingly accept or comprehend irreversible sterility as a side effect of therapy.
• Psychiatric illness, mental deficiency, or cognitive dysfunction severe enough to interfere with compliance or informed consent.
• History of hypersensitivity to rabbit or Escherichia coli-derived proteins.
• Any metallic material or electronic device in the body, or other condition that precludes the participant from undergoing MRI with gadolinium administration, as determined by the site radiologist.
• Presence or history of ischemic cerebrovascular disorders, including but not limited to transient ischemic attack, subarachnoid hemorrhage, cerebral thrombosis, cerebral embolism, or cerebral hemorrhage.
• Presence or history of other neurological disorders, including but not limited to CNS or spinal cord tumor; metabolic or infectious cause of myelopathy; genetically-inherited progressive CNS disorder; CNS sarcoidosis; or systemic autoimmune disorders potentially causing progressive neurologic disease or affecting ability to perform the study assessments.
• Presence of any medical comorbidity that the investigator determines will significantly increase the risk of treatment mortality.
• Presence of any other concomitant medical condition that the investigator deems incompatible with trial participation.
PROCEDURE: Autologous Hematopoietic Stem Cell Transplantation, BIOLOGICAL: Best Available Therapy (BAT)
Relapsing Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis
Treatment-Resistant Relapsing Multiple Sclerosis (MS), Autologous Hematopoietic Stem Cell Transplantation (AHSCT), Autologous Peripheral Blood Stem Cells (PBMCs) Graft, Best Available Therapy (BAT), Disease-Modifying Therapy (DMT), BAT DMT
UT Southwestern
Suicide Treatment Alternatives for Teens (START)
Quasi-Randomized trial to compare inpatient care versus outpatient crisis intervention clinic. This study plans to enroll up to 1,000 participants across 4 sites in a 5 years period.
Call 214-648-5005
studyfinder@utsouthwestern.edu, AMY.CONGER@UTSouthwestern.edu
Graham Emslie
ALL
12 Years to 18 Years old
NA
NCT04089254
STU-2023-0203
Inclusion Criteria:
• Adolescents that are 12 through 17 years old (including 17 year olds who will turn 18 years old during the course of the study).
• Are brought to the Emergency Department (ED) due to suicidal thoughts or behaviors
• Require a higher level of care (OCIC or Inpatient) indicated by clinician determination and a CHRT-SR score of 15 to 52.
• The presence of a legal guardian
• Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
• Adolescents with suicidal thoughts that place themselves at a serious imminent risk of suicide based on clinical judgment.
• Adolescents who require 24 hour/day supervision but no adult can provide 24 hour/day supervision outside of the hospital
• Adolescents without the ability to read and answer survey questions
• Adolescents that are non-English speaking due to the scales and surveys that are used for this study only being available in English.
BEHAVIORAL: Inpatient Psychiatry, BEHAVIORAL: Outpatient Crisis Intervention Clinic
Suicidal Ideation, Psychiatric Disorders
Suicide, Suicidal, Adolescent
Children’s Health
A Study of E7386 in Combination With Other Anticancer Drug in Participants With Solid Tumor
The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Miller
All
18 Years and over
Phase 1
NCT04008797
STU-2023-0509
Inclusion Criteria:
• HCC part only: Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
• Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection ST part only (except for HCC): Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
• Life expectancy of >=12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
• Adequate washout period before study drug administration:
• Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
• Any antitumor therapy with antibody: 4 weeks or more
• Any investigational drug or device: 4 weeks or more
• Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2 weeks or more Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis
• Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
• At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion Part) meeting following criteria
• At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI)
• Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/ transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
• For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted.
• For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
• For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below a. Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible
• For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment): Note: Adjuvant chemotherapy counts as prior systemic treatment if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible
• Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) (example, bevacizumab). Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment Note: Participants who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor
• Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat sarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible
• BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors
• Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC
• For EC Subpart in Expansion Part only: Participants who have radiographic evidence of disease progression after prior systemic therapies. Participants must have received platinum-based chemotherapy regimen and IO based regimen (example, lenvatinib + pembrolizumab or pembrolizumab monotherapy) for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting, but not exceeding 3 lines of therapies. If participants are ineligible for IO therapy, participants who have received only 1 prior systemic therapy including platinum based chemotherapy regimen are eligible Note: There is no restriction regarding prior hormonal therapy
Exclusion Criteria:
• Any of cardiac conditions as follows:
• Heart failure New York Heart Association (NYHA) Class II or above
• Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting study drug, or angina requiring use of nitrates more than once weekly)
• Prolongation of QT interval with Fridericias correction (QTcF) to greater than (>) 480 millisecond (msec)
• Left ventricular ejection fraction (LVEF) less than 50 percent (%)
• Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
• Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
• Participants with proteinuria >1 positive on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 gram per 24 hour will be ineligible
• Active infection requiring systemic treatment (Except for Hepatitis B and/or C [HBV/HCV] infection in HCC participants) In case of HBsAg (+) participants in HCC participants:
• Antiviral therapy for HBV is not ongoing
• HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the Screening Period although antiviral therapy for HBV is ongoing
• Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic acid [DNA]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic acid [RNA]) at study entry
• Diagnosed with meningeal carcinomatosis
• Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
• Any of bone disease/conditions as follows:
• Osteoporosis with T-score of < minus (-) 3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Participants with T-score <-2.5 to -3.0 and no prior medical therapy for osteoporosis can only be included if treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days prior to the first dose of study drug
• Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
• Symptomatic hypercalcemia requiring bisphosphonate therapy
• History of any fracture within 6 months prior to starting study drug
• Bone metastasis requiring orthopedic intervention
• Bone metastasis not being treated by bisphosphonate or denosumab. Participants may be included if treatment with bisphosphonate or denosumab has been started at least 14 days prior to the first dose of study drug. Participants with previous solitary bone lesions controlled with radiotherapy are eligible.
• History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
• Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline
• History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ [example, bladder or cervix]) within the past 24 months prior to the first dose of study drug
• For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more multiple dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive >=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 14 mg of lenvatinib due to toxicity
• Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only
• Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
• For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
• For EC Subpart in Expansion Part only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
• Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula
• Evidence of current COVID-19 infection or ongoing unrecovered active sequelae of COVID-19 infection
• Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 90 days after study drug discontinuation). No sperm donation is allowed during the study period and for 90 days after study drug discontinuation
• Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
• Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments
• Scheduled for major surgery during the study
Drug: E7386, Drug: Lenvatinib
Neoplasms, Carcinoma, Hepatocellular, Liver Neoplasms, Colorectal Neoplasms, Endometrial Neoplasms, Corpus Uteri, Colon, Liver
Solid Tumor, Hepatocellular carcinoma, Endometrial cancer, Colorectal cancer, E7386, Lenvatinib
UT Southwestern
89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE2
NCT04006522
STU-2019-0714
Inclusion Criteria:
* Patients with suspected renal cell carcinoma with planned surgery or patients with metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery).
* Ability to understand and the willingness to sign a written informed consent.
* Patient must be able to lie still for a 30 to 60 minute PET/CT scan.
* One of the following:
• Patients with locally advanced RCC planned for surgery determined to be a high risk of recurrence, defined by presence of at least clinical T2 or TxN1, OR patients with metastatic RCC for whom treatment with cytoreductive nephrectomy and/or metastasectomy is planned by the treating physician.
• Patients with metastatic RCC for whom immuno-oncology (IO) therapy is planned. * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of 89Zr-DFO-Atezolizumab administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to atezolizumab or any other chimeric or humanized antibodies.
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Significant autoimmune disease requiring treatment with either prednisone (or steroid equivalent) at a dose \> 10 mg/day or other immunosuppressive agents. (Replacement steroid therapy is acceptable).
* Any patient for whom ICI therapy would be contraindicated for other reasons. Patients with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab injection and PET/CT at the discretion of the treating physician considering that the dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to cause adverse events.
* Subjects unable to provide informed consent.
* Subjects who are claustrophobic or have other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed. (\>200 kg or 440 lbs). DRUG: 89Zr-DFO-Atezolizumab, PROCEDURE: Positron Emission Tomography/Computed Tomography
Renal Cell Carcinoma, Kidney
renal cell carcinoma, atezolizumab, PET/CT
UT Southwestern; Parkland Health & Hospital System
First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia
In this trial, ziftomenib, a menin-MLL(KMT2A) inhibitor, will be tested in patients for the first time. The trial includes a Main Study and four sub-studies. In the Main Study (including Phase 1a, Phase 1b, and Phase 2 portions), ziftomenib will be evaluated in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). The main study has completed enrollment. In Sub-studies 1 and 2, the effects of taking ziftomenib and other common drugs at the same time will be investigated in AML patients. In Sub-study 3, ziftomenib will be evaluated in patients with R/R acute lymphoblastic leukemia (ALL). In Sub-study 4, ziftomenib will be evaluated in patients with R/R AML with certain genetic mutations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
ALL
18 Years and over
PHASE1
NCT04067336
STU-2021-0258
Key
• Phase 1b: * Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Phase 2: * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Sub-studies: * Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression. * Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r. * Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
• Adequate liver and kidney function according to protocol requirements.
• Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment. Key
• Diagnosis of acute promyelocytic leukemia.
• Diagnosis of chronic myelogenous leukemia in blast crisis.
• Donor lymphocyte infusion \< 30 days prior to study entry.
• Clinically active central nervous system (CNS) leukemia.
• Undergone HSCT and have not had adequate hematologic recovery.
• Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
• Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
• Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
• Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
• Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows: * Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. * Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2).
• Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment.
• Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
• Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
• Mean QTcF \>480 ms on triplicate ECG.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment.
• For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1.
• For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
Inclusion Criteria:
Patients with refractory or relapsed AML defined as the reappearance of ≥ 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT.
• Phase 1b: * Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Phase 2: * Patients with a documented nucleophosmin 1 mutation (NPM1-m)
• Sub-studies: * Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression. * Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r. * Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.
• ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
• Adequate liver and kidney function according to protocol requirements.
• Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
• Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
• Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment. Key
Exclusion Criteria:
• Diagnosis of acute promyelocytic leukemia.
• Diagnosis of chronic myelogenous leukemia in blast crisis.
• Donor lymphocyte infusion \< 30 days prior to study entry.
• Clinically active central nervous system (CNS) leukemia.
• Undergone HSCT and have not had adequate hematologic recovery.
• Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
• Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
• Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
• Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
• Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows: * Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. * Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2).
• Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment.
• Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
• Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
• Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
• Mean QTcF \>480 ms on triplicate ECG.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment.
• For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1.
• For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
DRUG: Ziftomenib, DRUG: Midazolam, DRUG: Itraconazole
Advanced Malignant Neoplasm, Acute Myeloid Leukemia, Mixed Lineage Leukemia, Mixed Lineage Acute Leukemia, Acute Leukemia of Ambiguous Lineage, Mixed Phenotype Acute Leukemia, Acute Lymphoblastic Leukemia, Myeloid and Monocytic Leukemia
AML, Hematological malignancy, KMT2A, NPM1, Menin, Leukemia, Acute Leukemia, ALL, MLL, Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, MEIS1
UT Southwestern
A Trial to Evaluate Multiple Regimens in Newly Diagnosed and Recurrent Glioblastoma (GBM AGILE)
Glioblastoma (GBM) adaptive, global, innovative learning environment (GBM AGILE) is an international, seamless Phase II/III response adaptive randomization platform trial designed to evaluate multiple therapies in newly diagnosed (ND) and recurrent GBM.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Michael Youssef
ALL
18 Years and over
PHASE2
NCT03970447
STU-2019-1281
Newly Diagnosed
Inclusion Criteria:
* Age ≥ 18 years.
* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \[IHC\] or sequencing for IDH) established following either a surgical resection or biopsy. An MRI scan with the required imaging sequences performed within 21 days prior to randomization preferably. The post-operative MRI scan performed within 96 hours of surgery or the MRI scan performed for radiation therapy planning may serve as the MRI scan performed during screening if all required imaging sequences were obtained.
* Karnofsky performance status ≥ 60% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from definitive surgery or biopsy.
Recurrent Inclusion Criteria:
* Age ≥ 18 years.
* Histologically confirmed Grade IV GBM, inclusive of gliosarcoma (WHO criteria; IDH wild-type by immunohistochemistry \[IHC\] or sequencing for IDH) at first or second recurrence after initial standard, control or experimental therapy that includes at a minimum radiation therapy (RT).
* Evidence of recurrent disease demonstrated by disease progression using slightly modified Response Assessment in Neuro-Oncology (RANO) criteria.
* Two scans to confirm progression are required: at least 1 scan at the time of progression and 1 scan prior to the time of progression.
* Karnofsky performance status ≥ 70% performed within a 14-day window prior to randomization.
* Availability of tumor tissue representative of GBM from initial definitive surgery and/or, recurrent surgery, if performed.
Newly Diagnosed Exclusion Criteria:
* Received any prior treatment for glioma including: a. Prior prolifeprospan 20 with carmustine wafer. b. Prior intracerebral, intratumoral, or cerebral spinal fluid (CSF) agent. c. Prior radiation treatment for GBM or lower-grade glioma. d. Prior chemotherapy or immunotherapy for GBM or lower-grade glioma. Receiving additional, concurrent, active therapy for GBM outside of the trial.
* Extensive leptomeningeal disease.
* QTc \> 450 msec if male and QTc \> 470 msec if female.
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
Recurrent Exclusion Criteria:
* Early disease progression prior to 3 months (12 weeks) from the completion of RT.
* More than 2 prior lines for chemotherapy administration. (NOTE: In the 1st line adjuvant setting, combination of temozolomide (TMZ) with an experimental agent, is considered one line of chemotherapy.)
* Received any prior treatment with lomustine, agents part of any of the experimental arms, and bevacizumab or other vascular endothelial growth factor (VEGF) or VEGF receptor-mediated targeted agent.
* Any prior treatment with prolifeprospan 20 with carmustine wafer.
* Any prior treatment with an intracerebral agent.
* Receiving additional, concurrent, active therapy for GBM outside of the trial
* Extensive leptomeningeal disease.
* QTc \> 450 msec if male and QTc \> 470 msec if female.
* History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. DRUG: Temozolomide, DRUG: Lomustine, DRUG: Regorafenib, RADIATION: Radiation, DRUG: Paxalisib, DRUG: VAL-083, DRUG: VT1021, DRUG: Troriluzole, BIOLOGICAL: ADI-PEG 20, DRUG: AZD1390
Glioblastoma, Brain and Nervous System
Glioblastoma, Newly diagnosed, recurrent, O6-methylguanine-DNA-methyltransferase (MGMT) methylated, MGMT unmethylated, isocitrate dehydrogenase (IDH) wild-type, Bayesian, adaptive randomization, Master Protocol, Platform Trial, Phase 2, Phase 3
UT Southwestern
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy. The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-consolidation treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of delayed intensification. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
1 Year to 25 Years old
PHASE3
NCT03959085
STU-2019-1574
Inclusion Criteria:
* B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosis must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
* APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
* Patients must be \> 365 days and \< 25 years of age
* White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-9.99 years: WBC \>= 50,000/uL
* Age 10-24.99 years: Any WBC
* Age 1-9.99 years: WBC \< 50,000/uL with:
* Testicular leukemia
* CNS leukemia (CNS3)
* Steroid pretreatment.
* White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
* Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
* Patient has newly diagnosed B-ALL or MPAL (by World Health Organization \[WHO\] 2016 criteria) with \>= 25% blasts on a bone marrow (BM) aspirate;
* OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
* OR A complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
* Patient has newly diagnosed B-LLy Murphy stages III or IV.
* Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
* Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
* Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreduction. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.
Exclusion Criteria:
* Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL are eligible for AALL1731, regardless of NCI risk group).
* With the exception of steroid pretreatment and steroid cytoreduction or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for the current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1732.
* Patients who have received \> 72 hours of hydroxyurea within one week prior to start of systemic protocol therapy.
* Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted containing \> 1,000/uL circulating leukemia cells.
* Patients with acute undifferentiated leukemia (AUL) are not eligible.
* For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid pretreatment, the following additional exclusion criteria apply:
* T-lymphoblastic lymphoma.
* Morphologically unclassifiable lymphoma.
* Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
* Patients with known Charcot-Marie-Tooth disease.
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
* Patients requiring radiation at diagnosis.
* Female patients who are pregnant, since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating women who plan to breastfeed their infants while on study and for 2 months after the last dose of inotuzumab ozogamicin.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of study participation. For those patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the last dose of inotuzumab ozogamicin for females and 5 months after the last dose of inotuzumab ozogamicin for males. PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Bone Scan, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Inotuzumab Ozogamicin, DRUG: Leucovorin Calcium, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Pegaspargase, PROCEDURE: Positron Emission Tomography, DRUG: Prednisolone, OTHER: Questionnaire Administration, RADIATION: Radiation Therapy, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma, Central Nervous System Leukemia, Mixed Phenotype Acute Leukemia, Testicular Leukemia, Leukemia, Other
Children’s Health
Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hila.AbushSegev@UTSouthwestern.edu
Nader Pouratian
ALL
21 Years to 70 Years old
NA
NCT03952962
STU-2021-0635
Inclusion Criteria:
* Men and women (non-pregnant) between ages 21 and 70;
* DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less, recurrent or single episode with first episode after adulthood and did not start during childhood or adolescence, secondary to nonpsychotic unipolar major depressive disorder;
* Current index MDE ≥24 months duration and/or recurrent illness with at least a total of 2 lifetime episodes (including current episode \>12 months);
* Treatment resistance (defined by criteria on the Antidepressant Treatment History Form (ATHF)28): Failure to respond to a minimum of four adequate depression treatments from different categories;
* Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;
* Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one week pre-op;
* Normal brain MRI within 3 months of surgery;
* Antidepressant medication regimen has been held stable for ≥ 30 days prior to the study screening MADRS;
* Remain on stable antidepressant medication throughout the study, unless there are safety concerns;
* Montreal Cognitive Assessment (MoCA) \>25;
* Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months.
Exclusion Criteria:
* DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar disorder;
* Alcohol or substance use disorder within 6 months, excluding nicotine;
* History of childhood abuse (physical or sexual) 18
* Personality disorders;
* Seeking disability during the trial;
* Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the day of surgery);
* No stable work history;
* Neurological/Medical condition that makes the patient, in the opinion of the surgeon, a poor candidate;
• Pregnant or has plans to become pregnant in the next 36 months;
• Unable/unable to practice birth control through the period of randomization and withdrawal of therapy; * Subjects who have a history of a seizure disorder; * Subjects who will be exposed to diathermy; * Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery); * Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator; * Subjects who have a history of hemorrhagic stroke; * Subjects who are unable to undergo MRI; * Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.
DEVICE: Abbott Laboratories Infinity™ implantable deep brain stimulation system
Treatment Resistant Depression, Undergoing Deep Brain Stimulation (DBS) Surgery
UT Southwestern
Rituximab-pvvr and Abatacept vs Rituximab-pvvr Alone in New Onset Type 1 Diabetes (TN25)
The study is a two-arm, multicenter, double-blinded clinical trial testing sequential therapy with rituximab-pvvr followed by abatacept versus rituximab-pvvr alone in new onset T1D. The primary objective is to test whether the C-peptide response to a 2-hour mixed meal tolerance test, will be improved in participants with new onset T1D who are treated with Abatacept after Rituximab-pvvr compared to those treated with Rituximab-pvvr and placebo 24 months after enrollment.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Daniel.Peter@UTSouthwestern.edu
Perrin White
All
8 Years to 45 Years old
Phase 2
NCT03929601
STU-2019-1206
Inclusion Criteria:
• Age ≥ 8 and ≤ 45 years old at time of signing informed consent.
• Fulfill the ADA criteria for diagnosis of T1D within 100 days of randomization.
• Must be willing to provide informed consent or assent with a parent or legal guardian providing informed consent if < 18 years of age.
• Positive for at least one islet cell autoantibody; GAD65A, mIAA (if obtained within 10 days of the onset of insulin therapy), IA-2A, ICA, or ZnT8A
• Must have stimulated C-peptide of ≥0.2 pmol/mL measured during mixed-meal tolerance test (MMTT) conducted at least 21 days after the diagnosis of diabetes.
• Enrollees must be willing to comply with intensive diabetes management.
• Body weight must be ≥ 20.0 kg for study agent administration.
• Subjects who are CMV and/or EBV seronegative at screening must be CMV and/or EBV PCR negative and may not have had signs or symptoms of a CMV and/or EBV compatible illness prior to randomization.
• Female participants with reproductive potential must have a negative pregnancy test at screening and be willing to avoid pregnancy for the duration of treatment and until 3 months after the last dose of Abatacept. Female participants with reproductive potential who are sexually active will be instructed to use a highly effective contraceptive method until one year after the last dose of rituximab-pvvr.
• Male participants of reproductive age must use an adequate contraceptive method for the duration of rituximab-pvvr treatment and 12 months following the last dose of rituximab-pvvr.
• The following additional inclusion criteria regarding vaccines must be met:
• More than 4 weeks from immunization with a live viral vaccine
• Be up to date on all recommended vaccinations based on age of subject*
• Receive non-live influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
• Up to date, including eligible boosters as indicated for COVID-19 with an authorized non-live COVID-19 vaccination at least two weeks prior to randomization.
• Willingness to forgo vaccines (other than killed influenza) during the 6 months after the rituximab-pvvr treatment period
• Participants must be willing to practice public health prevention measures such as social distancing, masking, and good hand hygiene, and/or receive therapeutics such as monoclonal antibodies and antivirals as directed by the study and recommended by local health authorities to prevent SARS-Cov-2 infection.
• Willing to wear a continuous glucose monitoring device for a minimum of 10 days every 6 months * Adult subjects must be fully immunized. Pediatric subjects who have not completed their primary vaccination schedule must receive all vaccinations allowable per local public health immunization guidelines for their current age prior to study drug delivery. Any remaining vaccinations should be given and continue per the schedule at least 6 months after rituximab-pvvr is administered.
Exclusion Criteria:
• One or more screening laboratory values as stated:
• Leukocytes <3,000/μL
• Neutrophils <1,500/μL
• Lymphocytes <800/μL
• Platelets <100,000/μL
• Hemoglobin <6.2 mmol/L (10.0 g/dL)
• Potassium >5.5 mmol/L or <3.0 mmol/L
• Sodium >150 mmol/L or <130 mmol/L
• AST or ALT ≥ 2.5 times the upper limits of normal
• Bilirubin ≥ 1.5 times upper limit of normal
• History of immune deficiency
• Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening visit.
• Chronic active infection other than localized skin infections.
• Have active signs or symptoms of acute infection at the time of randomization.
• Have IgG and/or IgM levels below the normal reference ranges.
• Positive PPD, interferon gamma release assay (IGRA) or history of previous treatment for TB.
• Vaccination with a live virus within 4 weeks prior to initiating study treatment.
• A history of confirmed infectious mononucleosis within the 3 months prior to initiating study treatment, as documented by EBV serology (EBV VCA-IgM and VCA-IgG; PCR would be confirmatory).
• Laboratory evidence of current or past HIV or Hepatitis B or active Hepatitis C infection.
• Be currently pregnant, lactating or anticipate pregnancy within 14 weeks of the last study drug administration (Visit 15).
• Chronic use of oral or inhaled steroids or other immunosuppressive agents.
• Known and untreated hypothyroidism or active Graves' disease at randomization.
• History of malignancy.
• Prior treatment with active study agent from a previous clinical trial.
• Any laboratory abnormality or condition that, in the opinion of the investigator, would interfere with the study conduct or the safety of the participant.
Drug: Rituximab-pvvr, Drug: Abatacept, Drug: Sterile Sodium Chloride
Type 1 Diabetes Mellitus
UT Southwestern; Children’s Health
Markers of Osteoporosis in Cystic Fibrosis
Main Study Up to 100 subjects, both non-CF volunteers and Cystic Fibrosis (CF) patients, will participate in a single study visit that will include a DEXA scan, micro CT, and blood collection. Denosumab (Prolia) Sub study Approximately 10 adult subjects with CF who participated in the main study and have results indicating bone disease will receive treatment with Denosumab for up to 5 years. They will be asked to return annually for repeat DEXA scans, micro CT, and blood collection.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Maria.Mcleod@UTSouthwestern.edu
Raksha Jain
ALL
18 Years to 64 Years old
PHASE4
NCT03921060
STU 052018-007
Cystic Fibrosis Main Study
Inclusion Criteria:
* Must have CF diagnosis confirmed by sweat test or genotype analysis
* Subjects (and parents/legal guardians as applicable) must have the ability to read and write in English
Sub-study Exclusion Criteria:
* No CF diagnosis
* Men or women without osteoporosis
* Less than 18 years of age
* Unwilling to return annually for study visits for up to 5 years
* Unwilling and/or medically unable to take denosumab DRUG: Denosumab
Cystic Fibrosis, Bones and Joints, Lung/Thoracic
UT Southwestern; Children’s Health
Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis
This study is a non-randomized, open-label, partially blinded, sequential cohort, dose-escalation study designed to obtain preliminary data on the safety, tolerability, and early activity of Q-Cells® transplantation in subjects with Transverse Myelitis. For each of the dose levels, transplantation of Q-Cells® unilaterally into spinal cord demyelinated lesions will be evaluated. Subjects will be blinded to side of treatment. Idiopathic Transverse Myelitis is a monophasic disorder characterized predominantly by demyelination. Patients are left with disability from damage to ascending and descending white matter tracts. Q-Cells® are comprised of glial progenitor cells.It is postulated that the Q-Cells® glial progeny (healthy astrocytes and oligodendrocytes) will integrate into the spinal cord lesion site and remyelinate demyelinated axons as well as provide trophic support for damaged axons. Therefore, Q-Cells® have the potential to repair damage that has occurred and could be clinically useful for patients with disability caused by TM. The study is planned to enroll up to 9 subjects. Each subject will be followed for 9 months after transplantation of Q-Cells®. Each subject will receive a single time point administration of Q-Cells®: with transplantation foci targeted to posterior columns in the spinal cord (all transplantation foci below C7) on one side. Study participation consists of Screening, Pre-operative/Treatment, and Post-treatment study periods that will generally last from 9 to 12 months in total. The study data will be assessed for safety and activity until the last subject has completed the 9-month study visit. Following completion of the 9-month follow-up period, subjects who consent will continue to be followed for safety and activity in a separate long-term follow-up protocol.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taylor.Hinojo@UTSouthwestern.edu
Benjamin Greenberg
All
18 Years to 70 Years old
Phase 1/Phase 2
NCT03887273
STU 052017-076
Inclusion Criteria:
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to collect and use protected health information (PHI) in accordance with national and local subject privacy regulations.
• Live within reasonable travel distance to center or have reliable mechanism to travel to the center.
• Have a caregiver willing/able to assist in the transportation and care required by study participation.
• Subject is 18 - 70 years of age (inclusive) on day of Screening Visit.
• Subject is diagnosed with idiopathic TM within the past 120 months in accord with the Transverse Myelitis Consortium Working Group (2002).
• Subject has a MRI with a single focus of T2 hyperintensity that is 4 to 10 cm in length if no post contrast enhancement seen, or a single focus T1 post contrast enhancing lesion of 4 to 10 cm, with its most rostral extent at or below C8 myotome/dermatome level.
• Subject has negative NMO IgG (anti-AQP4) test at two separate time points, separated by at least 6 months.
• Subject has brain MRI not consistent with multiple sclerosis or other autoimmune or demyelinating disease.
• Subject is more than 12 months from TM onset.
• Subject has ASIA A categorization.
• Subject's neurological deficits related to TM have been stable for at least 3 months.
• Subject is medically able to undergo the study procedures and physically able to adhere to the visit schedule at the time of study entry.
• For women of child bearing capacity, negative pregnancy test during the Screening Period and at the Pre-Operative Visit.
• Males and females will agree to practice effective birth control during study participation and up to one year after.
Exclusion Criteria:
• Subject with causes of weakness, sensory loss and/or autonomic dysfunction other than TM have not been practically excluded.
• Subject with significant cognitive impairment, clinical dementia, or major psychiatric illness including psychosis, bipolar disease, major depression, as determined by the DSM-V.
• Subject with a diagnosis of a neurodegenerative disease (e.g., ALS, Parkinson's disease, Alzheimer's disease).
• Subject suffering with medical conditions that impair nerve or muscle function (e.g., notable peripheral neuropathy, metabolic muscle disease) or any disease or condition that would impair the subject's neuromuscular function or impair the adequate assessment of the subject's function (e.g., severe osteoarthritis).
• Subject with a clinically significant history of unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active malignancy or infectious disease or other medically significant illness that may render them at an unacceptable risk for surgery or that may cause them to be unable to complete the scheduled duration of the trial.
• History of spine surgery or anatomic variation incompatible with route of administration (as determined by neurosurgeon).
• Severe spinal stenosis or cord compression causing myelopathy.
• Abnormal flow voids on the surface of the spinal cord suggestive of arteriovenous malformation (AVM) or evidence of a vascular cause of a myelopathy (e.g., infarct of spinal artery).
• Any evidence of CNS malignancy or clinically significant CNS lesions as defined by imaging studies of the CNS (MRI of brain and spinal cord).
• Uncontrolled hypertension (Systolic BP>180mmHg and/or Diastolic BP >110mmHg).
• Any history of thrombotic or embolic events.
• Any poorly controlled medical conditions that, in the opinion of the site investigator and/or surgeon, increase risk of surgery to a medically unacceptable degree.
• Subjects who cannot undergo MRI examination because of any contraindication to the procedure, including the presence of a pacemaker, an implanted defibrillator or certain other implanted electronic or metallic devices, or who have been or might have been exposed to metal fragments, or any reason the subject cannot undergo an MRI routinely for the duration of the trial.
• Subject with clinically significant abnormal clinical laboratory values, as determined by the Investigator at the screening visit (Visit 1).
• Subject who is immune compromised (by therapeutic agent or disease) or who has a condition contraindicated to treatment with immunosuppression agents (e.g., tuberculosis, latent infection) as determined by history or testing. Any subject with an ongoing infection until it has been adequately treated and it is deemed to be resolved.
• Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value >3.0 times the upper limit of normal at the screening visit (Visit 1).
• Subject with diabetes or HgbA1c > 6.5
• Subject with a history of alcohol or drug abuse or dependence within 1 year of screening visit (Visit 1), per DSM-V criteria.
• Subject unlikely to comply with study requirements, as determined by Investigator.
• Subject who has been exposed to any other experimental agent (off-label use or investigational) within 60 days of screening visit (Visit 1). Biologic agents may need additional time for washout and will be evaluated by the Sponsor on a case-by-case basis.
• Subject with pre-existing anti-human leukocyte antigen (HLA) class I or class II antibodies directed against the Q-Cells®, as determined by panel reactive antibody (PRA) assay.
• Allergy to study treatment or any of its constituents (e.g., chicken eggs), or allergy to any of the co-administered immunosuppressants or any of their excipients.
• Subject with any medical condition or using concomitant medication that would contraindicate the use of tacrolimus, mycophenolate mofetil, or prednisone as determined by Investigator.
• Subject has undergone stem cell transplantation (including T-cell or bone marrow transplants) at any time prior to study (within or outside the US).
• Subject with evidence of deep vein thrombosis (DVT) by venous ultrasound or any previous evidence of DVT.
• Subject has recent (1 year) or recurrent history of gastrointestinal bleeding or peptic ulcer disease or is under active treatment to prevent recurrence.
• Subject with estimated glomerular filtration rate at screening of less than 60 mL/min/1.73m2.
• Subjects with hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.
• Vaccination with live virus within 6 weeks of screening.
• History or evidence of optic neuritis.
• Any reason, in the judgment of the investigator, which would make the subject inappropriate for entry into this trial.
Biological: Q-Cells
Transverse Myelitis, Brain and Nervous System
UT Southwestern
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT03866382
STU-2019-1012
Inclusion Criteria:
* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
* One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* One bone lesion on bone scan (tec99 or sodium fluoride \[NaF\] PET/CT, CT or MRI) for the bone-only cohort.
* Histologically confirmed diagnosis of one of the following metastatic cohorts:
* Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
* Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization \[WHO\] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma
* Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
* Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly \> or equal \~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
* Any penile cancer (Cohort E)
* Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid \~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed
* Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly \> or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly \> or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC
* Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
* Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly \~ 50% sarcomatoid differentiation
* Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains
* Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
* Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)
* Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
* H\&E slides from diagnostic tumor tissue for retrospective central pathology review
* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
* Age \>= 18 years
* Patients must be able to swallow oral formulation of the tablets
* Karnofsky performance status \>= 80%
* Absolute neutrophil count (ANC) \>= 1,000/mcL
* Platelet count \>= 75,000/mcL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =\< 3.0 mg/dL
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) (or =\< 5 x ULN for patients with liver metastases or Gilbert's disease)
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 40 mL/min/1.73 m\^2 (calculated using the Chronic Kidney Disease Epidemiology \[CKD-EPI\] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
* Hemoglobin \>= 9 g/dL (transfusion of packed red blood cells \[PRBCs\] allowed)
* Serum albumin \>= 3.2 g/dL
* Lipase and amylase =\< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
* No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil \[PTU\] or methimazole) including physiologic oral corticosteroids are eligible
* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
* Women of childbearing potential must have a negative pregnancy test =\< 7 days prior to registration
* Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea \>= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
* The patient has received no radiation therapy:
* To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
* To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To any other site(s) within 2 weeks before the first dose of study treatment
* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
* No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=\< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
* Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* The patient has not experienced any of the following:
* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
* Hemoptysis of \>= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
* The patient has no tumor invading any major blood vessels
* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible
* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Cardiovascular disorders including:
* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
* The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization. Note: if initial QTcF is found to be \> 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =\< 500 ms, the subject meets eligibility in this regard
* Any history of congenital long QT syndrome
* Any of the following within 6 months before registration of study treatment:
* Unstable angina pectoris
* Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
* Stroke (including transient ischemic attack \[TIA\], or other ischemic event)
* Myocardial infarction
* Cardiomyopathy
* No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
* Any of the following that have not resolved within 28 days before the first dose of study treatment:
* Active peptic ulcer disease
* Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
* None of the following within 2 years before the first dose of study treatment:
* Abdominal fistula or genitourinary fistula
* Gastrointestinal perforation
* Bowel obstruction or gastric outlet obstruction
* Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
* Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
* No other clinically significant disorders such as:
* Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
* Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
* History of organ or allogeneic stem cell transplant
* Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone \[TSH\], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
* No history of major surgery as follows:
* Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
* Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement
* Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
* No history of severe hypersensitivity reaction to any monoclonal antibody
* No evidence of active malignancy, requiring systemic treatment within 2 years of registration
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative
* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, BIOLOGICAL: Ipilimumab, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma, Bladder Mixed Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Bladder Squamous Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Collecting Duct Carcinoma, Invasive Bladder Giant Cell Urothelial Carcinoma, Invasive Bladder Lymphoepithelioma-Like Carcinoma, Invasive Bladder Nested Urothelial Carcinoma, Invasive Bladder Plasmacytoid Urothelial Carcinoma, Invasive Bladder Sarcomatoid Urothelial Carcinoma, Invasive Bladder Urothelial Carcinoma, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Malignant Testicular Leydig Cell Tumor, Malignant Testicular Sertoli Cell Tumor, Metastatic Bladder Carcinoma, Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma, Metastatic Bladder Giant Cell Urothelial Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Lipid-Rich Urothelial Carcinoma, Metastatic Bladder Micropapillary Urothelial Carcinoma, Metastatic Bladder Plasmacytoid Urothelial Carcinoma, Metastatic Bladder Sarcomatoid Urothelial Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Chromophobe Renal Cell Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Papillary Renal Cell Carcinoma, Metastatic Penile Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Metastatic Urethral Carcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Urachal Adenocarcinoma, Urethral Clear Cell Adenocarcinoma, Kidney, Other Male Genital, Other Urinary, Urinary Bladder
UT Southwestern
Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study
This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Therese.Vallina@UTSouthwestern.edu
Jeffrey Tessier
ALL
Not specified
PHASE3
NCT03808922
STU-2022-0991
Inclusion Criteria:
• At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
• Immunocompromised, as defined by one or more of the following: * Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past * Received a solid organ transplant at any time in the past * Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past * Has an immunodeficiency due to congenital abnormality (only applicable to subjects age \< 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
• Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus
• If female, subject must meet one of the following conditions: * Not be of childbearing potential or * Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception
• Non-vasectomized males are required to practice effective birth control methods
• Capable of understanding and complying with procedures as outlined in the protocol
• Provides signed informed consent prior to the initiation of any screening or study-specific procedures For COVID-19 sub study:
• Be ≥18 years of age
• Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised).
• Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL)
• Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung.
• Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples
• Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study
Exclusion Criteria:
• Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
• Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for \>1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
• Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
• Subjects taking any other investigational drug used to treat pulmonary infection.
• Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
• Subjects with known hypersensitivity to DAS181 and/or any of its components
• Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria: * Has evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Requires vasopressors to maintain blood pressure For COVID-19 sub study:
• Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization.
• Subjects receiving any other investigational or empiric treatment for SARS-2-CoV (either as part of a clinical trial or under emergency approval (approved agents for the management of symptoms, e.g., fever, are permitted).
• Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment)
• Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin)
• Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection and meeting at least one of the following criteria: * Have evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Require vasopressors to maintain blood pressure
• Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study
DRUG: DAS181, DRUG: Placebo, DRUG: DAS181 COVID-19, DRUG: DAS181 OL
Lower Respiratory Tract Infection, Parainfluenza, Immunocompromised, COVID-19, Lung/Thoracic
Parainfluenza, PIV, Immunocompromised, Lower Respiratory Tract Infection, LRTI, COVID19, SARS-CoV-2, Coronavirus, Ansun
UT Southwestern
Converting HR+ Breast Cancer Into an Individualized Vaccine (CBCV)
Newly diagnosed post-menopausal women with clinical stage II-III, HR+HER2- breast cancer are eligible to a randomized trial, concurrently open at five US academic institutions. Patients receiving 4 months of standard neoadjuvant hormonal therapy with letrozole are randomly assigned to one of 4 arms of a trial testing focal hypo-fractionated RT alone or with immunotherapy combinations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
FEMALE
18 Years to 90 Years old
PHASE2
NCT03804944
STU-2022-0463
Inclusion Criteria:
* Post-menopausal female ≥ 18 years of age (Post-menopausal status defined as either 1) at least 2 years without menstrual period or 2) or patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Biopsy proven diagnosis of ER+ PR+ or PR- HER2- breast cancer.
* Clinical stage I(\>1.5cm, if N0) - III breast cancer, as per AJCC staging 8th edition.
* Patient needs to be able to understand and demonstrate willingness to sign a written informed consent document.
Adequate bone marrow reserve and liver function:
WBC ≥ 2000/uL Absolute neutrophil count (ANC) ≥1500/μL Platelets ≥100 000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
Exclusion Criteria:
* Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy
* Current use of systemic chemotherapy, endoctine therap or HER2-neu targeted therapy
* Post surgical excision of breast cancer.
* Previous radiotherapy of the same breast.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
* Inability to obtain histologic proof of breast cancer
* Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
* Has a known history of active TB (Bacillus Tuberculosis). Note: optional based on country.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. RADIATION: Focal Radiation therapy, DRUG: Pembrolizumab (200mg IV for 30 minutes, BIOLOGICAL: CDX-301
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Trial of Curcumin to Prevent Progression of Low-risk Prostate Cancer Under Active Surveillance
This is a prospective study to determine if the use of curcumin randomized against placebo will reduce cancer progression in patients with prostate cancer undergoing active surveillance.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
MALE
40 Years to 89 Years old
PHASE3
NCT03769766
STU 012018-071
Inclusion Criteria:
* Age between 40-89 years
* Biopsy proven, low-risk, localized prostate cancer (minimum of 8 cores)
* May have had biopsy within last 12 months
* ≤4 separate locations in the prostate involved with cancer. If multiple cores are obtained from same lesion or area than this will count as one location.
* Gleason score ≤6 with no Gleason pattern 4
* Clinical stage T1c-T2a/b
* Serum PSA ≤15 ng/ml
* Life expectancy \> 5 years
Exclusion Criteria:
* Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy, oral glucocorticoids, GnRH analogues, prostatectomy)
* Concurrent or previous use within 6 months of screening of any 5α-reductase inhibitor
* Use of anabolic steroids or drugs with antiandrogenic properties
* Prostate volume \>150 cm³
* Patients who are taking antiplatelet, anticoagulant agents or have a history of a bleeding disorder. Patients taking 81 mg of Aspirin will be allowed to enroll with close observation
* History of gastric or duodenal ulcers or untreated hyperacidity syndromes. Patients on stable doses (2 months of therapy) of GERD medication allowed.
* Patients who are currently taking Curcumin and are unwilling to stop or plan to take Curcumin during the study
* Patients with a history of gallbladder problems or gallstones or biliary obstruction, unless patient had cholecystectomy DRUG: Curcumin, DRUG: Placebo
Prostate Cancer, Prostate
prostate cancer, active surveillance, curcumin
UT Southwestern; Parkland Health & Hospital System
Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair (TEF)
This trial will compare the effectiveness of two common surgical practices for Type C esophageal atresia repair: esophageal atresia (EA) with distal tracheoesophageal fistula (TEF). Infants with EA/TEF requiring surgical intervention will be recruited. Subjects will be randomized to either repair with or without transanstomotic tube (TT) during esophageal anastomosis creation. Primary outcome is symptomatic anastomotic stricture development requiring dilation within 12 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Aguas@UTSouthwestern.edu
Samir Pandya
All
up to 6 Months old
N/A
NCT03730454
STU-2020-1118
Inclusion Criteria:
• Infants diagnosed with type C esophageal atresia: proximal esophageal atresia and distal tracheoesophageal fistula
• Primary repair of the esophageal atresia within the first six months of life
• Minimum follow up of 1 year (12 months)
Exclusion Criteria:
• Other types of esophageal atresia without esophageal anastomosis creation
• Major anomaly that influences likelihood of developing primary outcome or affects surgical treatment considerations
Device: Transanastomotic Tube (5FR), Other: No Transanastomotic Tube
Esophageal Atresia, Tracheoesophageal Fistula, Esophagus
Children’s Health
Standard Systemic Therapy With or Without Definitive Treatment in Treating Participants With Metastatic Prostate Cancer
This phase III trial studies how well standard systemic therapy with or without definitive treatment (prostate removal surgery or radiation therapy) works in treating participants with prostate cancer that has spread to other places in the body. Addition of prostate removal surgery or radiation therapy to standard systemic therapy for prostate cancer may lower the chance of the cancer growing or spreading.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
MALE
18 Years and over
PHASE3
NCT03678025
STU-2020-0492
Inclusion Criteria:
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: All patients must have a histologically or cytologically proven diagnosis of adenocarcinoma of the prostate. Patients with pure small cell carcinoma\* (SCC), sarcomatoid, or squamous cell carcinoma are not eligible. (\*morphology must be consistent with SCC; synaptophysin or chromogranin positive by immunohistochemical staining is insufficient to diagnose SCC).
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have an intact prostate. No prior local therapy for prostate adenocarcinoma is allowed (e.g., brachytherapy, high-intensity focused ultrasound \[HIFU\], cryotherapy, laser ablative therapies). Any prior therapy for benign conditions, such as obstruction, are acceptable (e.g., transurethral resection of the prostate, greenlight laser ablation, microwave ablation).
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients must have evidence of metastatic disease on technetium bone scan and computed tomography (CT) or magnetic resonance imaging (MRI) within 42 days prior to starting standard systemic therapy. Metastatic disease that is detected by positron emission tomography (PET) scan only (sodium fluoride \[NaF\], prostate-specific membrane antigen \[PSMA\], anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid \[FACBC\], carbon \[C\]11) but not conventional imaging (technetium \[Tc\]99 bone scan, CT or MRI) or solitary metastases by conventional imaging, must be confirmed histologically or cytologically.
* STEP 1 REGISTRATION: DISEASE-RELATED CRITERIA: Patients with known brain metastases are not eligible. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received no more than 28 weeks of standard systemic therapy (SST). SST is defined as current National Comprehensive Cancer Network (NCCN) guidelines for metastatic prostate cancer.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not have progressed while on SST.
* STEP 1 REGISTRATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients with oligometastatic prostate cancer may receive metastasis directed therapy to up to four sites of disease prior to randomization.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a complete physical examination and medical history within 28 days prior to registration.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA documented prior to initiation of SST and within 28 days prior to registration. Any additional PSAs measured while receiving SST should be recorded.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone lab documented within 28 days prior to randomization. Any additional testosterone labs measured while receiving SST should be recorded as well as pretreatment initiation if available.
* STEP 1 REGISTRATION: CLINICAL/LABORATORY CRITERIA: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated stage 0, I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
* STEP 1 REGISTRATION: SPECIMEN SUBMISSION CRITERIA: Patients must be offered the opportunity to participate in translational medicine studies and specimen banking for future studies.
* STEP 1 REGISTRATION: QUALITY OF LIFE CRITERIA: Patients who can complete Patient-Reported Outcome instruments in English, Spanish or French, must participate in the quality of life studies.
* STEP 1 REGISTRATION: REGULATORY CRITERIA: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: 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.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have no evidence of disease progression during the 28 weeks of SST by PSA measure, bone scan and CT or MRI or symptomatic deterioration (as defined by physician discretion) within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: DISEASE-RELATED CRITERIA: Patients must have consultation with a urologist and have surgically resectable disease regardless of definitive treatment intent or randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must have received between 22 and 28 weeks of SST as measured from the date of first hormonal therapy or surgical castration. SST is defined by current NCCN guidelines for metastatic prostate cancer.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients must not be planning to receive docetaxel after randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Any toxicities from SST must have resolved to =\< grade 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) prior to randomization.
* STEP 2 RANDOMIZATION: PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have received elective metastasis directed therapy to oligometastatic sites (=\< 4 sites). All treatment must be completed prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a PSA performed within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a testosterone \< 50 ng/dL within 28 days prior to randomization.
* STEP 2 RANDOMIZATION: CLINICAL/LABORATORY CRITERIA: Patients must have a Zubrod performance status of 0 ? 1 within 28 days prior to randomization. DRUG: Abiraterone, DRUG: Bicalutamide, DRUG: Degarelix, DRUG: Docetaxel, DRUG: Flutamide, DRUG: Goserelin Acetate, DRUG: Histrelin Acetate, DRUG: Leuprolide Acetate, DRUG: Nilutamide, PROCEDURE: Orchiectomy, DRUG: Prednisone, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy, PROCEDURE: Radical Prostatectomy, DRUG: Triptorelin
Castration Levels of Testosterone, Metastatic Prostatic Adenocarcinoma, Stage IV Prostate Cancer AJCC v8, Stage IVA Prostate Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Prostate
UT Southwestern; Parkland Health & Hospital System
ExAblate Blood-Brain Barrier (BBB) Disruption for the Treatment of Alzheimer's Disease
The purpose of this study is to evaluate the safety and efficacy of the ExAblate Model 4000 Type 2.0 System as a tool to disrupt the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Charlton.Starcke@UTSouthwestern.edu
Bhavya Shah
ALL
50 Years to 85 Years old
NA
NCT03671889
STU-2020-0931
Inclusion Criteria:
• Male or Female between 50-85 years of age
• Probable Alzheimer's Disease (AD)
• If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months
• Able to communicate sensations during the ExAblate MRgFUS procedure
• Ambulatory
Exclusion Criteria:
• MRI Findings
• Presence of unknown or MR unsafe devices anywhere in the body
• Significant cardiac disease or unstable hemodynamic status
• Relative contraindications to ultrasound contrast agent or PET amyloid tracer
• History of a bleeding disorder
• History of liver disease
• Known cerebral or systemic vasculopathy
• Significant depression and at potential risk of suicide
• Any contraindications to MRI scanning
• Any contraindication to lumbar puncture for collection of cerebral spinal fluid
• Untreated, uncontrolled sleep apnea
• History of seizure disorder or epilepsy
• Severely Impaired renal function
• Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research
• Chronic pulmonary disorders
• Positive human immunodeficiency virus (HIV)
• Known apolipoprotein E allele (ApoE4) homozygosity
DEVICE: Blood Brain Barrier (BBB) Disruption
Alzheimer Disease, Brain and Nervous System
Alzheimer Disease, Alzheimer Syndrome, Magnetic Resonance guided Focal Ultrasound (MRgFUS), Blood-Brain Barrier, ExAblate
UT Southwestern
Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Triple-negative Breast Cancer
The purpose of this study is to determine the impact of pre-operative cryoablation, and immune checkpoint inhibition (ICI) on on 3-year Event Free Survival (EFS), in women with residual hormone receptor negative, HER2-negative ("triple negative") resectable breast cancer after taxane-based neoadjuvant chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
FEMALE
18 Years and over
PHASE2
NCT03546686
STU-2021-1043
Inclusion Criteria:
• Women age 18 years or older
• Confirmed histologic diagnosis of invasive carcinoma of the breast
• Pathology confirmation of invasive carcinoma (reported or requested and pending)
• ER, PR and HER2 negative on outside or Cedars Sinai biopsy report, where ER and PR negative are defined as staining present in ≤10% of invasive cancer cells by IHC, and HER2-negative is defined as IHC 0-1+ or FISH \<2.0. If ER, PR and HER2 status are not reported the results must be requested and pending.
• Operable tumor measuring ≥1.0 cm in maximal diameter
• Any nodal status allowed, including negative nodal status.
• Multifocal and multicentric disease is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• Synchronous bilateral invasive breast cancer is permitted if all foci have been biopsied and also meet the criteria for TNBC.
• No indication of distant metastases
• Total mastectomy or lumpectomy planned
• Tumor amenable to cryoablation as determined by a study radiologist
• ECOG performance status score of 0 or 1.
• Screening laboratory values must meet the following criteria: * White blood cells (WBCs) ≥ 2000/μL * Absolute neutrophil count (ANC) ≥ 1500/μL * Platelets ≥ 100 x 103/μL ii. Hemoglobin ≥ 9.0 g/dL iii. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL * AST/ALT ≤ 3 x upper limit of normal (ULN) * Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL)
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab and, ipilimumab, and pembrolizumab to undergo five half-lives) after the last dose of investigational drug.
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). Women must not be breastfeeding
• Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
Exclusion Criteria:
* Medical history and concurrent diseases
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent or poorly controlled diarrhea.
• A history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer, or ovarian cancer.
• Has known active hepatitis B or hepatitis C. * Prohibited Treatments and/or Therapies
• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). Brief periods of steroid use, for example for the management of chemotherapy-associated toxicities, are allowed. The use of corticosteroids on study is allowed for the treatment of immune related adverse events (irAEs) and other medical conditions including adrenal insufficiency.
• Any non-oncology live vaccine therapy used for prevention of infectious diseases within 3 weeks prior to first dose of ICI.
• Prior investigational agents within 3 weeks prior to ICI administration
DRUG: Pembrolizumab, PROCEDURE: Core Biopsy/Cryoablation, PROCEDURE: Breast Surgery, DRUG: Ipilimumab, DRUG: Nivolumab
Breast Cancer, Breast - Female
Hormone Receptor Negative, Her2- Negative, Resectable Breast Cancer, breast cancer, immunotherapy, Ipilimumab, Nivolumab, Cryoablation
UT Southwestern; Parkland Health & Hospital System
Regional Radiotherapy in Biomarker Low-Risk Node Positive and T3N0 Breast Cancer (TAILOR RT)
The purpose of this study is to compare the effects on low risk breast cancer receiving usual care that includes regional radiation therapy, with receiving no regional radiation therapy. Researchers want to see if not giving this type of radiation treatment works as well at preventing breast cancer from coming back.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Ann Leitch
FEMALE
35 Years and over
PHASE3
NCT03488693
STU-2018-0236
Inclusion Criteria:
* Patients must be women with newly diagnosed histologically proven invasive carcinoma of the breast with no evidence of metastases, staged as per site standard of care.
* Patients must have been treated by BCS or mastectomy with clear margins of excision. Post-mastectomy positive margins for invasive disease and/or DCIS is not allowed. Multifocal disease (i.e. the presence of two or more foci or breast cancer within the same breast quadrant) and multicentric disease (i.e. the presence of two or more foci of breast cancer in different quadrants of the same breast) are allowed.
* Patients with T3N0 disease are eligible.
* Patients with disease limited to nodal micrometastases are eligible
* Patients with nodal macrometastases (\>2mm) treated by axillary dissection must have 1-3 positive axillary nodes (macrometastases, \> 2 mm).
* Patients treated by mastectomy and SLNB alone must have only 1-2 positive axillary nodes (macrometastases, \> 2 mm).
* Patients must be ER ≥ 1% and HER2 negative on local testing
* Patients must have an Oncotype DX recurrence score ≤25 obtained from testing of breast tumour tissue from a core biopsy or from the surgical specimen.
* Patient must consent to provision of, and investigator(s) must agree to submit to the CCTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the specific correlative marker assays described in the protocol may be conducted
* Patient must consent to provision of samples of blood in order that the specific correlative marker assays described in the protocol may be conducted.
* Patients must have had endocrine therapy initiated or planned for ≥ 5 years. Premenopausal women will receive ovarian ablation plus aromatase inhibitor therapy or tamoxifen if adjuvant chemotherapy was not administered. For all patients, endocrine therapy can be given concurrently or following RT.
* Patients may or may not have had adjuvant chemotherapy.
* RT must commence within 16 weeks of definitive surgery if the patient is not treated with chemotherapy. If adjuvant chemotherapy is given, RT must begin within 12 weeks after the last dose. (Note: adjuvant chemotherapy may be ongoing at the time of randomization). Definitive surgery is defined as the last breast cancer-related surgery.
* Patient's ECOG performance status must be 0, 1 or 2.
* Patient's age must be ≥ 35 years.
* For the first 736 eligible English or French-speaking subjects who have agreed to optional questionnaire completion: Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life, health utilities and lost productivity questionnaires in either English or French (note: enrollment completed 2022Aug02)
* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* In accordance with CCTG policy, protocol treatment is to begin within 6 weeks of patient randomization.
* Women of childbearing potential must have agreed to use an effective contraceptive method. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months.
Exclusion Criteria:
* Patients with nodal disease limited to isolated tumour cells (pN0i+ \< 0.2 mm).
* Patients with pT3N1 and pT4 disease (Note: patients with T3N0 are eligible).
* Any prior history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated with radiation therapy. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
* Synchronous or previous contralateral invasive breast cancer. (Patients with contralateral DCIS are eligible unless previously treated with radiation.)
* History of non-breast malignancies except adequately treated non-melanoma skin cancers, in situ cancers treated by local excision or other cancers curatively treated with no evidence of disease for ≥ 5 years.
* Patients who are pregnant.
* Patients that have had prior ipsilateral chestwall/thoracic radiation.
* Patients treated with chemo or endocrine therapy administered in the neoadjuvant setting for breast cancer. Endocrine therapy exposure 12 weeks or less prior to surgery is permitted.
* Patients with serious non-malignant disease (e.g. cardiovascular, scleroderma etc.) which would preclude RT.
* Patients with any serious active or co-morbid medical conditions, laboratory abnormality, psychiatric illness, active or uncontrolled infections, or serious illnesses or medical conditions that would prevent the patient from participating or to be managed according to the protocol (according to investigator's decision). RADIATION: Radiation, OTHER: No Radiation
Breast Cancer, Breast - Female
UT Southwestern; Parkland Health & Hospital System
Dystonia Genotype-Phenotype Correlation
The purpose of this study is to (1) investigate the effect of known dystonia-causing mutations on brain structure and function, to (2) identify structural brain changes that differ between clinical phenotypes of dystonia, and to (3) collect DNA, detailed family history, and clinical phenotypes from patients with idiopathic dystonia with the goal of identifying new dystonia-related genes. Investigators will be recruiting both healthy control subjects and subjects with any form of dystonia. For this study there will be a maximum of two study visit involving a clinical assessment, collection of medical and family history, task training session, an MRI using the learned tasks, and finally a blood draw for genetic analysis. In total, these visits will take 3-5 hours. If the dystonia subjects receive botulinum toxin injections for treatment, the participants and their matched controls will be asked to come for a second visit.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Boudreau@UTSouthwestern.edu
Jeffrey Waugh
ALL
11 Years and over
NCT03428009
STU 122017-069
General Exclusion (both Dystonia and Control groups):
* Metal in any part of the body (including metal injury to the eye) OR carrying a medical device incompatible with MRI (e.g., metal implants such as surgical clips or pacemakers) OR positive screening per UTSW MRI screening form
* Claustrophobia
* Non-fluent English
* Weight incompatible with MRI safety
* History of head trauma with neurological sequelae, including multiple concussions and/or history of stroke
* Pregnancy
* Serious medical illness or history of serious medical illness, including cancer that was treated with radiation or chemotherapy, heart attack, or a known history of HIV-1 + status
* Subjects with Hepatitis C (by Hepatitis C+ titer)
* Subjects with insulin dependent diabetes mellitus (IDDM)
* Severe respiratory compromise
* In the opinion of the investigator, not able to safely participate in this study
Inclusion Criteria:
* Dystonia group
Previous diagnosis of dystonia which include but is not limited to:
* cervical dystonia (50 subjects)
* blepharospasm (25 subjects)
* limb dystonia (50 subjects)
* spasmodic dysphonia (25 subjects)
* segmental dystonia
* multi-focal dystonia
* Any childhood-onset dystonia (25 subjects) Age \> 11 years
* Control group:
No prior dystonia diagnosis (175 subjects) Age \> 11 years
Exclusion Criteria:
* Dystonia group Prior history of or concurrent neurological or psychiatric diagnosis - depression and/or anxiety accepted Current use of non-dystonia neuroactive medications - SSRI/medication for depression and/or anxiety accepted Current use of cervical brace designed for dystonia treatment Prior structural brain injury
Control group:
History of or current neurological or psychiatric diagnosis - depression and/or anxiety accepted, but must not be in active phase Current use of any neuroactive medication, SSRI/medication for depression and/or anxiety accepted OTHER: Magnetic Resonance Imaging
Dystonia, Dystonia, Idiopathic, Dystonia, Primary, Dystonia, Secondary, Dystonia, Familial, Dystonia Disorder, Dystonias, Sporadic, Dystonia, Orofacial, Dystonia Lenticularis, Dystonia, Paroxysmal, Dystonia 6, Dystonia 5, Dystonia 8, Dystonia 9, Dystonia 19, Dystonia 10, Dystonia 11, Dystonia 20, Dystonia 12, Dystonia, Focal, Dystonia of Head, Dystonia, Diurnal
Dystonia, Control, Magnetic Resonance Imagine, Genotype, Phenotype
UT Southwestern; Children’s Health
Neurocognitive Decline in Patients With Brain Metastases
The phase I component of the study is to identify maximal tolerated dose (MTD). The phase II is to evaluate neurocognitive decline.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Zabihullah Wardak
ALL
18 Years and over
PHASE1
NCT03508752
STU 122016-064
Inclusion Criteria:
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better.
• Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study.
• Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging.
• Largest tumor \<= 4 cm.
• No prior SRS to the lesions which will be treated on protocol.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Prior whole brain radiotherapy
• Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.)
• Patients with life expectancy \< 4 months.
• Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
RADIATION: Stereotactic Radiosurgery
Brain Metastases, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Adoptive Cell Therapy Long-term Follow-up (LTFU) Study
This trial will evaluate long term safety of participants who have received AdaptImmune (ADP) adoptive cell therapy for up to 15 years following last adoptive cell therapy infusion.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Samuel John
ALL
4 Years and over
PHASE1
NCT03391778
STU-2019-1522
Inclusion Criteria:
* Participants who have received at least one dose of ADP adoptive cell therapy agent.
* Participants who have completed ADP sponsored or supported interventional study or have withdrawn from it.
* Participants who have completed treatment as part of managed access to a GSK adoptive cell therapy.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* The investigator is responsible for review of medical history.
* Capable of giving signed informed consent.
Exclusion Criteria:
• None
BIOLOGICAL: ADP adoptive cell therapy
Neoplasms, Soft Tissue
Long Term Follow Up, Adoptive Cell Therapy, Replication Competent Lentivirus
Children’s Health
S1501 Dual Observational and Randomized Cohort Study of Patients With Metastatic HER-2+ Breast Cancer at Risk of Cardiac Toxicity
This trial has two cohorts of patients with human epidermal growth factor receptor (HER)-2-positive breast cancer that has spread to other places in the body. All patients must be receiving trastuzumab-based treatment. Both cohorts are being observed for cardiac toxicity. The largest cohort (currently open to accrual) is observational, and contains patients who are taking a beta blocker, ACE inhibitor, or ARB as well as their trastuzumab-based treatment. The goal is to understand how common cardiac problems are in this group of patients at high risk. The smaller cohort (currently closed to accrual) is randomized. Patients in this second cohort are randomized to either carvedilol or no treatment, with the goal of seeing whether carvedilol (used to treat heart failure and high blood pressure) may prevent the heart from side effects of chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vlad Zaha
ALL
18 Years and over
PHASE3
NCT03418961
STU-2021-1112
Inclusion Criteria:
* STEP 1 REGISTRATION
Patients must:
• Have metastatic breast cancer, AND
• Be initiating within 11 calendar days of Step 1 Registration OR be continuing trastuzumab-based HER-2 targeted therapy without concurrent anthracyclines, AND
• Be receiving the trastuzumab-based HER-2 targeted therapy for metastatic disease in first, second, third-, or fourth-line setting. Patients may have brain metastasis. There is no limit for number of doses of HER-2 targeted therapy prior to registration. Examples of eligible HER-2 targeted therapy: * Trastuzumab or a trastuzumab biosimilar * Trastuzumab + chemotherapy or hormonal therapy * Trastuzumab + other HER-2 targeted agent with or without chemotherapy (such as pertuzumab, lapatinib, and tucatinib) * Ado-trastuzumab (Kadcyla®) * Fam-trastuzumab deruxtecan (Enhertu) NOTE: Patients on lapatinib without trastuzumab are not eligible. Planned treatment with concurrent HER-2 targeted therapy and anthracyclines is not permitted. * Patients must be at increased risk for cardiotoxicity defined by at least one of the following:
• Previous anthracycline exposure OR
• 1 or more of the following risk factors for heart disease: * LVEF 50-54% by local ECHO read\* * Age ≥ 65 * BMI ≥ 30 kg/m2 * Current or prior anti-hypertensive therapy * Diagnosis of coronary artery disease (CAD) * Diagnosis of diabetes mellitus * Diagnosis of atrial fibrillation/flutter Note: ECHO can be performed at any time prior to registration with the most recent being sent. * Patients must not have taken within 21 days prior to Step 1 Registration, be currently taking at the time of Step 1 Registration or planning to take once registered to Step 1 a beta blocker, ARB, or ACE inhibitor, in order to be randomized (Arms 1 and 2). Patients enrolling in the observational cohort (Arm 3) must be currently taking a beta blocker, ARB, or ACE inhibitor at the time of Step 1 Registration. * Patients must have a Zubrod Performance status of 0-2 * Patients must have a complete physical examination and medical history within 28 days prior to registration * Patients must have LVEF \>= 50% echocardiogram (2D or 3D) within 28 days prior to registration. The echocardiogram must be obtained from a S1501 validated ECHO laboratory (lab) and submitted for central review by the S1501 ECHO core lab. If a 3D echocardiogram is performed at baseline, sites must ensure that standard 2D images, including 40chamber and 2-chamber views, are also obtained and submitted at subsequent timepoints. All follow-up echocardiograms (every 12 weeks) must be performed using 2D imaging to allow for standardized assessments. Follow-up scans must be completed at a site that can provide 2D images per protocol requirements. The echocardiograms cannot be submitted for central read until after Step 1 registration is complete. * Patients must have adequate hepatic function as evidenced by all of the following within 28 days prior to registration: * Serum bilirubin \< 3.0 x institutional upper limit of normal (IULN) * Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) and serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) \< 5.0 x IULN * Patients must not be dialysis dependent * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer on active surveillance, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years * Patients must not be pregnant or nursing due to potential fetal or nursing infant harm; women/men of reproductive potential must have agreed to use an effective contraceptive method, a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * Patients must be willing to submit blood specimens * Sites must seek additional patient consent for the future use of specimens * Patients must be informed of the investigational nature of this study and must sign and give written 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 CIRB regulations. * 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 * STEP 2 REGISTRATION (Randomization) * Patients must not be registered to step 2 until confirming via RAVE EDC that the patient's LVEF by echocardiogram was \>= 50% by central review. Patients must be registered within 21 calendar days of submission of the ECHO study/ * Site must verify that there is no known change in the step 1 eligibility since initial registration
DRUG: Carvedilol, OTHER: Laboratory Biomarker Analysis, OTHER: Patient Observation
Cardiotoxicity, HER2/Neu Positive, Metastatic Malignant Neoplasm in the Brain, Recurrent Breast Carcinoma, Stage IV Breast Cancer AJCC v6 and v7, Breast - Female
UT Southwestern
A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy (ALLELE)
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
Not specified
PHASE3
NCT03394365
STU-2018-0349
Inclusion Criteria:
• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT).
• A diagnosis of locally assessed, biopsy-proven EBV+ PTLD.
• Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor.
• Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used. For participants with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
• Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants \< 16 years.
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the participant underwent transplant must be in morphologic remission.
• Adequate organ function.
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support.
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the participant has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each \< 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction.
• Participant or participant's representative is willing and able to provide written informed consent.
Exclusion Criteria:
• Currently active Burkitt, T-cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
• Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis.
• Untreated CNS PTLD or CNS PTLD for which the participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment.
• Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment.
• For C-HCT: active adenovirus viremia.
• Need for vasopressor or ventilatory support.
• Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment.
• Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only).
• Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception.
• Inability to comply with study-related procedures.
• Any medical condition or organ system dysfunction that in the investigator';s opinion, could compromise the participant's safety or ability to complete the study.
BIOLOGICAL: tabelecleucel
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications, Other
Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy
Children’s Health