StudyFinder
Search Results
652 Study Matches
A Study to Compare Treatment With the Drug Selumetinib Alone Versus Selumetinib and Vinblastine in Patients With Recurrent or Progressive Low-Grade Glioma
This phase III trial investigates the best dose of vinblastine in combination with selumetinib and the benefit of adding vinblastine to selumetinib compared to selumetinib alone in treating children and young adults with low-grade glioma (a common type of brain cancer) that has come back after prior treatment (recurrent) or does not respond to therapy (progressive). Selumetinib is a drug that works by blocking a protein that lets tumor cells grow without stopping. Vinblastine blocks cell growth by stopping cell division and may kill cancer cells. Giving selumetinib in combination with vinblastine may work better than selumetinib alone in treating recurrent or progressive low-grade glioma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Daniel Bowers
10760
ALL
2 Years to 25 Years old
PHASE3
NCT04576117
STU-2021-0019
Inclusion Criteria:
* Feasibility phase: patients must be \>= 2 years and =\< 21 years of age at the time of enrollment
* Efficacy phase: patients must be \>= 2 years and =\< 25 years of age at the time of enrollment
* All patients \> 21 years of age at the time of enrollment must have had initial diagnosis of low-grade glioma by 21 years of age
* Patients must have a body surface area (BSA) of \>= 0.5 m\^2 at enrollment
* Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1
* Non-neurofibromatosis type 1 (non-NF1), non-tuberous sclerosis complex (non-TSC) low-grade glioma (LGG) without a BRAFV600E or IDH1 mutation
* Patients must have progressive or recurrent LGG. Note: Biopsy may be at either initial diagnosis or recurrence
* Patients must have measurable disease, defined as having a two-dimensional measurable tumor volume of \>= 1 cm\^2
* Tumor size will be measured to include both solid and cystic components of the tumor (whether or not tumor is enhancing) + fluid attenuated inversion recovery (FLAIR) signal
* Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (World Health Organization \[WHO\] grade 1 and II) by the WHO Classification of Tumors of the Central Nervous System - 4th Edition Revised, with the exception of subependymal giant cell astrocytoma
* Patients with metastatic disease or multiple independent primary LGGs are eligible
* Patients must be progressive or recurrent after having been treated with at least one prior tumor-directed therapy before enrollment
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea);
* Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent;
* Radiation therapy (RT): \>= 2 weeks (wks) for local palliative RT (small port); \>= 6 months must have elapsed if prior craniospinal RT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation;
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to =\< grade 1;
* MEK inhibitor or vinblastine: Must not have received treatment with a MEK inhibitor or vinblastine within 6 months of study enrollment
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^ 2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
* 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 (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 (within 7 days prior to enrollment)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Albumin \>= 2 g/L (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 (within 4 weeks prior to enrollment)
* Corrected QT interval (QTc interval) =\< 450 msec by electrocardiogram (EKG) (within 4 weeks prior to enrollment)
* Absolute neutrophil count \>= 1,000/uL (unsupported) (within 7 days prior to enrollment)
* Platelets \>= 100,000/uL (unsupported) (within 7 days prior to enrollment)
* Hemoglobin \>= 8 g/dL (may be supported) (within 7 days prior to enrollment)
* Patients with a known seizure disorder should be stable and should not have experienced a significant increase in seizure frequency within 2 weeks prior to enrollment
* Stable neurological examination for \>= 1 week
* HYPERTENSION:
* Patients 2-17 years of age must have a blood pressure that is =\< 95th percentile for age, height, and gender 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 4 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 4 weeks prior to enrollment
* Note: If surgical resection or biopsy is performed at the time of progression or recurrence, a post-operative MRI is required
* 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
Exclusion Criteria:
* Prior therapy with vinblastine and/or a MEK inhibitor is permitted, with the following exceptions:
* Patients must not have had progressive disease while on therapy with vinblastine or a MEK inhibitor;
* Patients must not have discontinued vinblastine or selumetinib due to toxicity
* 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 must not have known hypersensitivity to selumetinib, vinblastine, or similar compounds
* CYP3A4 agents: Patients must not have received fluconazole or drugs that are strong inducers or inhibitors of CYP3A4 within 7 days prior to study enrollment
* 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
* PRE-EXISTING CONDITIONS (CARDIAC):
* 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 Heart Association (NYHA) class II-IV prior or current cardiomyopathy
* Severe valvular heart disease
* History of atrial fibrillation
* PRE-EXISTING CONDITIONS (OPHTHALMOLOGIC CONDITIONS):
* 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 upper limit of normal (ULN) adjusted by age are not eligible
* Any multivitamin containing vitamin E must be stopped prior to study enrollment even if it contains less than 100% of the daily recommended dosing for vitamin E
* Surgery within 2 weeks prior to enrollment, with the exception of a surgical biopsy, placement of a vascular access device or cerebrospinal 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
* 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
* 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 12 weeks after stopping study therapy are not eligible
* Note: Women of child-bearing potential and males with sexual partners who are pregnant or who could become pregnant (i.e., women of child-bearing potential) should use effective methods of contraception for the duration of the study and for 12 weeks after stopping study therapy to avoid pregnancy and/or potential adverse effects on the developing embryo
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, PROCEDURE: Magnetic Resonance Imaging, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Selumetinib Sulfate, DRUG: Vinblastine Sulfate
Recurrent Low Grade Astrocytoma, Refractory Low Grade Astrocytoma, Refractory Low Grade Glioma, Recurrent WHO Grade 2 Glioma, Refractory WHO Grade 1 Glioma
Children’s Health
CLOZAPINE Response in Biotype-1
The CLOZAPINE study is designed as a multisite study across 5 sites and is a clinical trial, involving human participants who are prospectively assigned to an intervention. The study will utilize a stringent randomized, double-blinded, parallel group clinical trial design. B2 group will serve as psychosis control with risperidone as medication control. The study is designed to evaluate effect of clozapine on the B1 participants, and the effect that will be evaluated is a biomedical outcome. The study sample will be comprised of individuals with psychosis, including 1) schizophrenia, 2) schizoaffective disorder and 3) psychotic bipolar I disorder. The investigators plan to initially screen and recruit n=524 (from both the existing B-SNIP library and newly-identified psychosis cases, ~50% each) in order to enroll n=320 (B1 and B2) into the RCT.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Asha.Philip@UTSouthwestern.edu
Carol Tamminga
58406
ALL
18 Years to 60 Years old
PHASE4
NCT04580134
STU-2020-0989
Inclusion Criteria:
* 18-60y/o; males and females; all races and ethnicities; able to provide written informed consent; able to read, speak, and understand English; medically stable; meeting DSM-IV (SCID-based) criteria for schizophrenia, schizoaffective disorder, or bipolar I disorder with psychotic features (we will use DSM-IV to be consistent with prior B-SNIP samples); PANSS total score of ≥70 and at least one item scored ≥5 or two items scored ≥4 on PANSS Positive Subscale; normal baseline values for absolute neutrophil count (ANC above 1500/mm3)
Exclusion Criteria:
* premorbid intellectual ability estimate below 70 (WRAT-4, Word Reading subtest, age-corrected standardized score); comorbid DSM-IV diagnosis of alcohol or substance abuse in prior 1 month or substance dependence in prior 3 months; neurological (e.g., seizure disorder, stroke, traumatic brain injury with a loss of consciousness ≥ 30min) or severe medical condition (e.g., decompensated cardiovascular disorder, AIDS) that may affect central nervous system function; concomitant medications known to affect EEG properties (i.e., lithium, anticonvulsants, benzodiazepines) or strong CYP 1A2 inhibitors (e.g., ciprofloxacin, enoxacin) or strong CYP 3A4 inducers (e.g., phenytoin, carbamazepine, phenobarbital, rifampin) which cannot be safely discontinued; vulnerable populations (e.g., pregnant, nursing, incarcerated); unwilling to use reliable means of contraception; history of neuroleptic malignant syndrome; prior treatment with clozapine, prior treatment with long-acting injectable antipsychotics that are 1-month formulations within the past 3 months and for 3-month formulations within the past 6 months; intolerable side effects to either clozapine or risperidone in lifetime, or a previously failed trial of either clozapine or risperidone at adequate doses in lifetime; history of drug reaction with eosinophilia and systemic symptoms syndrome (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS); high risk for suicide defined as more than 1 attempt in past 12 months that required medical attention, any attempt in the past 3 months or current suicidal ideation with plan and intent such that outpatient care is precluded; current homicidal ideation with plan and intent such that outpatient care is precluded. DRUG: clozapine, DRUG: risperidone
Schizophrenia, Schizoaffective Disorder, Bipolar 1 Disorder
Schizophrenia, Bipolar, Psychosis, Biomarker, Biotype, BSNIP, B-SNIP, IEA
UT Southwestern
FUVID Study: Functional Characterization of Children With Chronic Venous Thromboembolic Disease
This is a multi-center prospective cohort study of patients with first-episode deep venous thrombosis and pulmonary embolism.
Call 214-648-5005
studyfinder@utsouthwestern.edu, kendra.malone@childrens.com, FUVID@utsouthwestern.edu
Ayesha Zia
149180
ALL
8 Years to 21 Years old
NCT04583878
STU-2020-0868
Inclusion Criteria:
* Ages 8 to ≤ 21 years
* Participant must be able to speak and understand English
* Be willing to participate and able to comply with the study protocol
* For participants with PE: Children with acute, radiologically confirmed pulmonary embolism (PE) with our without DVT
* For control group: Cohort 1: Children who are prescribed physical activity restrictions for 2 up to 12 weeks following any minor outpatient surgery or, minor injury (surgery or injury is referred to as "diagnosis" hereafter) Cohort 2: Children who are not prescribed physical activity restrictions and are otherwise considered to be healthy.
Exclusion Criteria:
* Congenital heart disease with abnormal pulmonary circulation or with in-situ pulmonary artery thrombosis
* Chronic kidney disease
* Chronic inflammatory or an autoimmune disorder (such as systemic lupus erythematosus, juvenile rheumatoid disorder, inflammatory bowel disease, and sickle cell disease)
* A metabolic or endocrinological disorder such as diabetes mellitus or thyroid disorder
* History of or active cancer
* Pregnant
* Musculoskeletal limitations to exercise expected to be present uptil 4 months post-diagnosis
* Weight ≥ 300 lbs
* Contraindications to magnetic resonance imaging
* Frequent severe exacerbations of asthma defined by two or more bursts of systemic glucocorticoids (more than three days each) in the previous year or at least one hospitalization, intensive care unit stay or mechanical ventilation in the previous year. Patients should also be excluded if there are daily symptoms of asthma requiring daily use of short-acting bronchodilators such as albuterol or levalbuterol administration. The use of controller medications such as daily inhaled corticosteroids for mild persistent asthma is not exclusionary.
* Has any other medical condition, which in the opinion of the investigator may potentially compromise the safety or compliance of the patient or may preclude the patient's successful completion of the clinical study
Additional exclusion criteria for participants with PE:
* Prior history of DVT or PE (upper extremity, cerebral sinus venous thrombosis and abdominal thromboses encountered as a neonate are not exclusion criteria)
* Lack of anticoagulant treatment for the acute VTE due to contraindications DIAGNOSTIC_TEST: Blood draw (Visit 1), DIAGNOSTIC_TEST: Blood draw (Visits 2 and 3)
Pulmonary Embolism, Deep Venous Thrombosis
UT Southwestern; Children’s Health; Parkland Health & Hospital System
A Study to Evaluate Tabelecleucel in Participants With Epstein-barr Virus-associated Diseases
The purpose of this study is to assess the efficacy and safety of tabelecleucel in participants with Epstein-Barr virus (EBV) associated diseases.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Victor Aquino
10208
All
Not specified
Phase 2
NCT04554914
STU-2020-0614
Inclusion Criteria:
• Diagnosis of EBV+ disorder
• Eastern Cooperative Oncology Group performance status <= 3 for participants aged >= 16 years; Lansky score >= 20 for participants from >=1 year to < 16 years
• Adequate organ function test results, unless organ dysfunction is considered to be due to the underlying EBV-associated disease by the investigator Cohort-specific
Inclusion Criteria:
• For participants with PID LPD:
• R/R or newly diagnosed PID LPD for whom the standard first-line therapy is inappropriate, as determined by investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive cerebrospinal fluid (CSF) cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification (Cheson BD, et al. J Clin Oncol. 2014;27:3059) during or after treatment or failure to achieve a CR or partial response (PR) (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
• For participants with AID LPD:
• R/R or newly diagnosed AID LPD for whom the standard first line therapy is inappropriate, as determined by the investigator. The LPD is confirmed by at least biopsy-proven EBV+ LPD or positive CSF cytology, with or without radiographically measurable intracranial disease, with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic disease only, systemic and CNS disease, or CNS disease only
• For participants with AID etiology or AID attributable to immunosenescence, objective laboratory evidence of immunodeficiency
• For participants with CNS PTLD:
• R/R or newly diagnosed EBV+ CNS PTLD for whom the standard first-line therapy is inappropriate, as determined by the investigator. The CNS PTLD is histologically confirmed by at least biopsy-proven EBV+ CNS PTLD or positive CSF cytology with or without radiographically measurable intracranial disease with EBV detected in CSF.
• Participants with R/R disease must have had at least one prior line of systemic therapy and one of the following: radiographic disease progression per Lugano Classification during or after treatment or failure to achieve a CR or PR (defined by Lugano radiographic criteria) after standard first-line therapy
• Participant may have systemic and CNS disease or CNS disease only
• For participants with EBV+ PTLD, including CD20-negative disease:
• Biopsy-proven EBV+ PTLD for whom standard first-line therapy (rituximab and/or chemotherapy) is inappropriate, as determined by the investigator
• Participants must have systemic disease measurable per Lugano Classification criteria, except when contraindicated or mandated by local practice, then MRI may be used
• For participants with sarcoma, including LMS, or smooth muscle tumors:
• EBV+ sarcoma or smooth muscle tumor with rapidly progressive disease defined as progressive disease per RECIST 1.1 criteria as documented radiographically within a 6-month interval prior to enrollment
• Participants with newly diagnosed EBV+ sarcoma for whom the standard first-line therapy is inappropriate, as determined by the investigator
• Biopsy-proven EBV+ sarcoma meeting one of the criteria's of pathologically confirmed EBV+ Leiomyosarcoma or EBV+ sarcoma or smooth muscle tumor
• Measurable disease using diagnostic CT and/or MRI following RECIST 1.1 criteria (Eisenhauer et al. 2009. Eur J Cancer 45[2]:228-247)
Exclusion Criteria:
• Currently active Burkitt, T-cell, natural killer/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy
• Serious known active infections, defined as ongoing uncontrolled adenovirus infection or infections requiring systemic therapy at the time of enrollment, or known history of human immunodeficiency virus (HIV) infection
• Suspected or confirmed Grade >= 2 acute graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research (CIBMTR) consensus grading system or extensive chronic GvHD per National Institutes of Health (NIH) consensus criteria at the time of the enrollment
• Need for vasopressor or ventilatory support at the time of enrollment
• Prior therapy (in order of increasing washout period) prior to enrollment as follows:
• Within 4 weeks or 5 half-lives (whichever is shorter) for any investigational product and/ or any chemotherapy (systemic or intrathecal), targeted small molecule therapy, or antibody/biologic therapy. Note: prior anti-CD20 antibody use is permitted within the washout period if a subsequent disease response assessment indicates disease progression
• Within 8 weeks: prior tabelecleucel (>8 weeks prior to enrollment) is permitted if response was obtained or if usual protocol-directed therapeutic options were not exhausted, for cellular therapies (chimeric antigen receptor therapies directed at T-cells or T-cell subsets, donor lymphocyte infusion, other CTLs or virus-specific T-cells); and/or therapies which could impact tabelecleucel function (anti-thymocyte globulin, alemtuzumab)
• Any prior treatment with EBV-CTLs with the exception of tabelecleucel as above
• Women who are breastfeeding or pregnant
• Unwilling to comply with protocol specified contraceptive/reproductive restrictions from enrollment through 90 days after the last treatment
• Ongoing need for daily steroids of > 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis (for participants with CNS disease, protocol-specified dexamethasone is permitted and concludes by the time of enrollment)
• Any conditions that may put the study outcomes at undue risk (life expectancy < 60 days or any life-threatening illness, medical condition, or organ system dysfunction)
• For participants with PID LPD or AID LPD: history of prior allogeneic HCT or solid organ transplant
• For participants with EBV+ PTLD: prior systemic therapy for PTLD
Biological: Tabelecleucel
Sarcoma, Leiomyosarcoma, Stem Cell Transplant Complications, Lymphoproliferative Disorders, Solid Organ Transplant Complications, Allogeneic Hematopoietic Cell Transplant, Brain and Nervous System, Epstein-Barr Virus (EBV)-Associated Diseases, EBV+ Post-transplant Lymphoproliferative Disease (EBV+ PTLD), EBV+ Sarcomas, EBV+ Lymphoproliferative Disease With Primary Immunodeficiency (EBV+ PID LPD), EBV+ Lymphoproliferative Disease With Acquired (Non-congenital) Immunodeficiency (EBV+ AID LPD), EBV+ Posttransplant Lymphoproliferative Disease in Central Nervous System (EBV+ CNS PTLD)
Allogeneic, Off-The-Shelf T-cell Immunotherapy, Epstein-Barr Virus (EBV), Epstein-Barr Virus-specific Cytotoxic T lymphocyte (EBV-CTL), Solid Organ Transplant (SOT), Hematopoietic Cell Transplant (HCT), EBVision
Children’s Health
Youth Depression and Suicide Research Network (YDSRN)
The objective of this study is to build the Texas Youth Depression and Suicide Research Network to support the development of a Network Participant Registry and characterization of systems and interventions to examine statewide population health outcomes. All 12-13 sites represented in the Texas Child Mental Health Care Consortium (https://www.utsystem.edu/pophealth/tcmhcc/) have been invited to participate in the Texas Youth Depression and Suicide Research Network as "Nodes." 12 Nodes have been selected for this project. Each Node has obtained support of senior institutional leadership including the department chair. Leadership from each Node provided input and edits in the study design process by committee, with a focus on the inclusion of the "end user" in design decisions. Nodes will work closely with the Network Hub leadership to recruit, monitor, and retain participants. This will require active engagement and sustained relationships with clinics within the academic medical center as well as clinics in the community (i.e., psychiatry, psychology, counselling).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Holli.Slater@UTSouthwestern.edu
Madhukar Trivedi
17410
ALL
8 Years to 20 Years old
NCT04572321
STU-2020-0665
Inclusion Criteria:
• Be 8 to 20 years of age;
• Have a positive screen for depression (e.g., based on PHQ-2 (score ≥3) and/or PHQ-A of 10 or greater, OR positive for suicidal ideation or behavior (e.g., based on CHRT-SR or PHQ-A item 9); OR be in treatment for depression;
• Be willing to provide consent/assent (parents/LAR/guardian or young adult participant, aged 18-20, must be willing to provide consent; youth, aged 8-17, must be willing to provide assent);
• Be able to speak English or Spanish sufficiently to understand the study procedures and provide written informed consent to participate in the study;
• Be willing to dedicate appropriate time to complete scheduled study assessments and measures (both parent/LAR/guardian and youth).
• Be able to provide a reliable means of contact.
Exclusion Criteria:
• Have an acute medical or psychological condition(s) that that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
• Have an acute medical or psychological condition(s) that would result in an inability to accurately complete study requirements (e.g., neurological conditions or significant neurodevelopmental concerns);
• Have active psychotic symptoms resulting in altered mental status and inability to provide assent or requiring immediate attention and/or higher level of intervention;
• Have a parent/LAR/guardian who is deemed cognitively unable to provide consent (if youth participant, aged 8-17).
Depression, Suicidal Ideation, Suicide, Attempted, Depressive Disorder, Suicide, Depressive Episode, Depressive Symptoms, Depression and Suicide, Depression, Teen, Depression, Anxiety
depression, suicide, suicidal ideation, suicide attempt, teen, child, depressive episode, depression in teens
Children’s Health
Use Of A Response-Adapted Ruxolitinib-Containing Regimen For The Treatment Of Hemophagocytic Lymphohistiocytosis
This study is a multi-site Phase Ib/II, 2-arm non-randomized clinical trial to determine the efficacy and tolerability of a response-adapted regimen combining ruxolitinib, dexamethasone, and etoposide as Frontline therapy for patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH) or as Salvage therapy for patients with relapsed/refractory HLH. Primary Objective - To determine the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with newly diagnosed HLH. Secondary Objectives - To describe the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for patients with relapsed/refractory HLH. - To describe the overall response and outcome for patients with newly diagnosed or relapsed/refractory HLH who are treated with this response-adapted ruxolitinib-containing regimen. Exploratory Objectives - To estimate the pharmacokinetic (PK) parameters of ruxolitinib, assess covariates of ruxolitinib pharmacokinetics, and test whether the drug's effectiveness is correlated with systemic drug exposure. - To query specific immunologic biomarkers and determine whether the levels of these biomarkers correlate with disease response and outcome.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jessica.Quicano@childrens.com
Erin Butler
104034
All
6 Weeks to 22 Years old
Phase 1/Phase 2
NCT04551131
STU-2023-0217
Inclusion Criteria:
Frontline Arm:
• Patient is ≥6 weeks and ≤22 years of age.
• Patient weighs ≥3 kg.
• Patient is able to take medication PO and/or patient or parent is willing to have NG tube placed if patient is unable to take medications PO.
• Patient has active HLH if:
• Patient has ≥5 of 8 Diagnostic HLH criteria listed below, OR
• Patient has known fHLH (e.g., patient has pathogenic/likely pathogenic germline variant(s) in genes such as PRF1, UNC13D, STX11, STXBP2, LYST, RAB27A, XIAP, SH2D1A, NLCR4) and meets ≥4 of the diagnostic HLH criteria listed below, OR
• Patient has high likelihood of fHLH based on absent perforin, SAP, XIAP expression and meets ≥4 of the Diagnostic HLH Criteria listed below:
• Fever
• Splenomegaly (If present at any point prior to starting study drug)
• Cytopenias affecting ≥2 of 3 cell lineages in the peripheral blood (hemoglobin <9 g/dL, platelets <100 × 10^9/L, ANC <1000/mm^3)
• Hypertriglyceridemia (fasting triglycerides ≥265 mg/dL) or hypofibrinogenemia (fibrinogen ≤150 mg/dL)
• Presence of hemophagocytosis in BM or other tissues
• Low or absent NK-cell activity (if present at any point prior to starting study drug) OR decreased CD107a mobilization (if present at any point prior to starting study drug)
• Ferritin ≥500 ng/mL
• Soluble IL-2 receptor (CD25) ≥2400 U/mL
• Patient has not received prior HLH therapy, except steroids (any dose or length of therapy is allowed) OR anakinra (any dose or length of therapy is allowed).
• Patient, parent, or legal authorized representative (LAR) must provide informed consent.
Inclusion Criteria:
Salvage Arm:
• Patient is ≥6 weeks and ≤22 years of age.
• Patient weighs ≥3 kg.
• Patient or parent is willing to have the NG tube placed if patient is unable to take medications PO.
• Patient has past history of HLH, defined as meeting ≥5 of 8 HLH- 2004 diagnostic criteria for those with no known HLH-associated mutations, OR ≥4 of 8 HLH-2004 diagnostic criteria for those with known familial disease.
• Patient must have active HLH at the time of eligibility assessment, defined as 3 or more of the following Relapsed/Refractory HLH Criteria:
• Fever
• Splenomegaly (recurrent or worsening)
• ANC <1000/mm^3 × 2 assessments over at least 3 days OR platelets <100 × 10^9/L × 2 assessments over at least 3 days, OR need for platelet transfusions
• Hypofibrinogenemia (fibrinogen ≤150 mg/dL)
• Soluble IL-2 receptor level ≥ 2400 U/mL
• Worsening CNS symptoms OR new abnormal brain magnetic resonance imaging (MRI) findings deemed consistent with CNS HLH by the primary treating physician OR CSF cell count ≥5 mm^3 (with or without hemophagocytosis) OR CSF protein higher than the institutional upper limit of normal OR CSF neopterin higher than the institutional upper limit of normal
• Presence of hemophagocytosis in the BM or other tissues
• Increasing ferritin × 2 assessments over at least 3 days (both levels must be ≥2000 ng/mL)
• Patient must be deemed by the primary treating physician to have not responded to prior therapy by either not having or maintaining a response
• Patient must have received prior HLH-directed therapy:
• At least 2 weeks of steroids (equivalent to at least 5 mg/m^2/day dexamethasone or 1 mg/kg/day methylprednisolone) AND at least 2 doses of etoposide; OR
• At least 1 dose of ATG
• Patient or parent/LAR must provide informed consent. Laboratory findings must be given on at least 2 assessments, each completed at least 1 day apart, EXCEPT CNS radiologic/laboratory findings in which a single abnormal value is sufficient.
Exclusion Criteria:
Frontline and Salvage Arms:
• Patient is <6 weeks or >22 years of age.
• Patient weighs <3 kg.
• Patient has isolated CNS disease.
• Life expectancy is <2 weeks.
• Patient is likely to require <4 weeks of therapy (i.e., HSCT is imminent).
• Patients with creatinine clearance (CrCl) <15 mL/min who are NOT receiving dialysis.
• Patient has evidence of severe organ dysfunction, defined as: Severe liver dysfunction (ALT >1000 U/L), OR Cardiorespiratory failure requiring any ionotropic support OR extracorporeal life support, OR high frequency oscillatory ventilation, other forms of respiratory support or ventilation are allowed if the patient is not on vasopressors)
• Patient with pre-existing rheumatologic disorder.
• Patient with known active malignancy.
• Patient with previous HSCT, except when HSCT was for treatment of HLH.
• Patient is pregnant or lactating.
• Patients who expect to conceive or father children within the projected duration of the study and/or who are unwilling to use highly effective methods of contraception throughout the duration of the study, starting with the screening visit through the end of the treatment visit.
• Patient has suspected or known fungal disease.
• Patient is unable to tolerate administration of drugs PO or NG.
• Patient is taking rifampin or St. John's Wort.
• Patient is taking another investigational agent or is enrolled on another treatment protocol.
• Patient, parent, or LAR are unable or unwilling to provide informed consent. Additional Exclusion Criteria for the Frontline Arm:
• Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib), ATG, alemtuzumab, etoposide, tocilizumab, emapalumab or any other HLH-directed therapy other than steroids or anakinra (as defined in the Frontline Arm Inclusion Criteria, #5). Additional Exclusion Criteria for the Salvage Arm:
• Patient has or is receiving treatment with a JAK inhibitor (including ruxolitinib) or alemtuzumab within the last 3 months.
• Patient has received therapy on the Frontline Arm of this trial.
Drug: Ruxolitinib, Drug: Dexamethasone, Drug: Etoposide
Hemophagocytic Lymphohistiocytosis, Other Hematopoietic
Hemophagocytic lymphohistiocytosis, Newly Diagnosed, Frontline therapy, Refractory, Relapsed, Response-adapted, Salvage therapy
Children’s Health
A Phase II Trial of Poly-ICLC for Low-Grade Gliomas (NF111)
This is a phase II, prospective, longitudinal, multi-center trial of poly-ICLC (Hiltonol ®) treatment for progressive low-grade gliomas in pediatric patients with NF1. The primary objective is to evaluate the efficacy of poly-ICLC in pediatric NF1 patients with progressive low-grade glioma (LGG) as measured by objective tumor response rate (CR+PR) within the first 48 weeks (12 cycles) of therapy. There will also be secondary and exploratory objectives listed in the detailed description below.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
13954
All
up to 22 Years old
Phase 2
NCT04544007
STU-2021-0062
Inclusion Criteria:
• Age: Patients must be less than 22 years at the time of enrollment; there is no lower age limit.
• All participants must have an identified pathogenetic constitutional NF1 mutation OR the clinical diagnosis of NF1 using the NIH Consensus Conference criteria.
• Diagnosis: LGG (WHO Grade 1 and 2) of the brain and spinal cord are eligible. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings. Biopsy for histologic diagnosis is required if there is clinical suspicion for a high-grade tumor; special attention is recommended in older adolescents or young adults to the potential for malignant transformation. Patients with metastatic disease are eligible.
• Patients must meet at least one of the following criteria for progression or recurrence of a previously treated target tumor:
• Progression or recurrence on MRI.
• New or worsening neurologic symptoms attributable to the target tumor.
• For patients with OPG: visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year by examination or history, attributable to tumor.
• Measurable Disease: Patients must have two-dimensional measurable tumor >1cm2.
• Prior Therapy: Patients must have had at least one prior medical treatment for the target LGG.
• Performance Level: Patients must have a performance status of equal or > than 50 using Karnofsky for patients equal or ≥ 16 years of age and Lansky for patients < 16 years of age.
• Patients must have recovered to grade ≤1 from any acute toxicities from all prior treatments. to enroll on this study and meet time restrictions from end of prior therapy as defined below:
• Myelosuppressive chemotherapy: must have received the last dose of myelosuppressive therapy at least 4 weeks prior to study registration, or at least 6 weeks if nitrosourea.
• Investigational/biological agent: Patient must have received the last dose of other investigational, immunotherapy, or biological agent > 14 days prior to study registration or at least 5 half-lives, whichever is greater. Bevacizumab last dose > 36 days prior to enrollment.
• Radiation therapy: Patients SHOULD NOT have received prior irradiation.
• Study specific limitations on prior therapy: There is no limit on the number of prior treatment regimens.
• Growth factor(s): Must not have received any hematopoietic growth factors within 7 days of study entry or > 14 days if pegylated GCSF is used.
• Prior surgery: At the time of enrollment, must be ≥ 3 weeks from prior major surgery such as craniotomy, orthopedic surgery, abdominal surgery or ≥1 week from minor surgery and completely recovered. Port or central line placement is not considered a major surgery.
• Organ Function Requirements: All patients must have adequate organ function defined as:
• 1 Hematologic Function:
• Hemoglobin: > 8.0 gm/dl (may transfuse PRBCs)
• ANC: > 750/mm3. Must be at least 7 days after last dose of growth factor or > 14 days since last dose of pegylated GCSF
• Platelet Count: > 75,000/mm3 (transfusion independent; ≥ 7 days from last transfusion)
• 2 Renal Function: Serum creatinine which is less than 1.5 times ULN for age (as per the table below) or GFR > 70 ml/min/1.73m2 Renal Function Normal for Age Age Maximum Serum Creatinine (mg/dL) Male Female 1 month to < 6 months 0.4 0.4 6 months to < 1 year 0.5 0.5 1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1 1 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 ≥ 16 years 1.7 1.4 Liver Function:
• Total bilirubin < 1.5 x ULN (Children with diagnosis of Gilbert's Syndrome will be allowed on the study regardless of their total and indirect bilirubin levels as long as the direct bilirubin is less than 3.1 mg/dL.)
• SGPT (ALT) ≤ 5 x ULN
• SGOT (AST) ≤ 5 x ULN Pulmonary Function: No evidence of dyspnea at rest, and a pulse oximetry ≥ 92%. Reproductive Function: Female patients of childbearing potential must have negative serum or urine pregnancy test within 7 days prior to the first dose of poly-ICLC. Patient must not be pregnant or breast-feeding. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, including abstinence, while being treated on this study and for 90 days following cessation of treatment.
• Patient is able to start treatment within 7 days after enrollment.
• Patients with neurological deficits must be stable for a minimum of 1 week prior to enrollment.
• Patients are only eligible if complete resection of the LGG with acceptable morbidity is not feasible, or if a patient with a surgical option refuses surgery.
• Parents/legal guardians must provide written informed consent and agree that they will comply with the study.
Exclusion Criteria:
• Prior radiation treatment for the low-grade glioma.
• Prior exposure to poly-ICLC.
• Patients currently receiving other anti-tumor therapy or experimental therapy (targeted agents, chemotherapy radiation).
• Patients with a current or prior diagnosis of malignant glioma (WHO grade III or IV).
• Patients with a prior diagnosis of malignant peripheral nerve sheath tumor or other malignancy requiring treatment in the last 48 months.
• Patients may not have fever (≥38.50 C) within 3 days of enrollment.
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
• Active auto-immune illness.
• Pregnant or lactating females.
• 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 90 days after stopping study therapy are not eligible.
• Severe unresolved infection that requires systemic IV antibiotics.
• Patients with any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, impaired gastrointestinal function, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients requiring high doses of steroids. Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as ≤ 0.75 mg/m2/day dexamethasone or equivalent) at time of enrollment. However, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
Drug: Poly ICLC
NF1, Brain and Nervous System, Low-grade Glioma
Children’s Health
Feasibility and Effectiveness of Real-time, Remote Continuous Glucose Monitoring in Adolescents With Poorly Controlled Type 1 Diabetes
Adolescents with Type 1 Diabetes (age 13-18 years, T1D duration >6 months managed on insulin) and poor glycemic control will wear a blinded CGM to obtain baseline data. After assuring adherence to CGM wear, participants will receive a non-blinded CGM and will share their blood glucose levels with the study team. Clinical personnel will remotely monitor patients in real-time for 3 months and communicate regularly over secure text messaging with participants and their parents. Following active remote monitoring, the participants will wear a non-blinded CGM for 3 months. Primary outcome assessment will be the change in HbA1c after 3 months of real-time remote continuous glucose monitoring.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Michelle.Murphy@UTSouthwestern.edu
Abha Choudhary
162494
All
13 Years to 18 Years old
N/A
NCT04540536
STU-2020-0699
Inclusion Criteria:
• Age between 13-18
• Diagnosis of type 1 diabetes for at least six months.
• Both sexes and all ethnicities included.
• Subject and at least one parent able to communicate in English.
• Poorly controlled T1D as evidenced by a >40% annual risk of developing DKA in the following year
• Treated with subcutaneous insulin, either with a basal/bolus insulin regimen or a continuous subcutaneous insulin infusion (CSII) device.
• Willing to wear CGM and utilize the share function to clinician and guardian, with measuring blood glucose checks as required by the CGM.
• Owning a smartphone compatible with Dexcom G6 software to allow the use of share/follow features with internet access capabilities
• Willing to participate in secure text messaging with study personnel.
• Female participants must have a negative pregnancy test.
Exclusion Criteria:
• Type 2 diabetes, secondary diabetes or CF related diabetes.
• Other severe chronic disease (e.g., cancer) which in the judgment of the investigator is likely to significantly affect glycemic control.
• Patients cannot be taking systemic corticosteroids at enrollment because of adverse effects on glycemic control, but we will not disqualify subjects who require such therapy during the study. Inhaled or topical corticosteroids are permissible.
• Patients with hypothyroidism or hyperthyroidism must be clinically euthyroid and have free T4 and TSH within age-appropriate reference ranges at last medically indicated testing. Patients with out of range values may be retested after medication dose adjustment.
• Developmental delay or behavioral disorder in the patient of sufficient severity, in the judgment of the investigator, to interfere with study activities. Severe uncontrolled depression defined as PHQ-9A >9 at time of enrollment is an exclusion criterion.
• Medical or psychiatric disorder in a parent of sufficient severity, in the judgment of the investigator, to interfere with study activities.
• Regular CGM for the month preceding study period.
• Pregnancy, planned pregnancy or breast feeding
• CGM adhesive allergy
• Skin condition that makes CGM placement contraindicated.
• Sickle cell disease or hemoglobinopathy
• Red blood cell transfusion within 3 months prior to study enrollment
Other: Continuous Glucose Monitoring, Other: Secure texting
Diabetes Mellitus, Type 1, Noncompliance, Patient
Type 1 Diabetes, Continuous Glucose Monitors, Telemedicine, Remote Monitoring, Secure Texting, Poorly controlled diabetes
Children’s Health
A Phase I/II Study of VTX-801 in Adult Patients With Wilson's Disease (GATEWAY)
The objectives of this clinical trial are to assess, for up to 5 years, the safety, tolerability and pharmacological activity of a single ascending doses of VTX-801, a gene therapy, administered intravenously (IV) to adult patients with Wilson's Disease prior to and following background WD therapy withdrawal.
Call 214-648-5005
studyfinder@utsouthwestern.edu, NAHID.ATTAR@UTSouthwestern.edu
William Lee
14217
All
18 Years to 65 Years old
Phase 1/Phase 2
NCT04537377
STU-2022-0533
Main
• Male or female aged 18 and 65 years inclusive
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for inadequate treatment
• Stable WD for ≥ 1 year, defined as: (i) No significant change in neurologic examination and in status of mood disorder and (ii) Stable laboratory parameters used to assess copper metabolism Main
• ALT level ≥ 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN
• INR > 1.2
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrollment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60 mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index ≥ 35 kg/m2 Other protocol defined Inclusion/ Exclusion criteria may apply
Inclusion Criteria:
• Male or female aged 18 and 65 years inclusive
• Confirmed diagnosis of WD
• Treated for WD according to international recommendations with no current evidence for inadequate treatment
• Stable WD for ≥ 1 year, defined as: (i) No significant change in neurologic examination and in status of mood disorder and (ii) Stable laboratory parameters used to assess copper metabolism Main
Exclusion Criteria:
• ALT level ≥ 2 ULN that is not readily explained by extrinsic factors
• Total bilirubin > 1.5 x ULN in the absence of proven Gilbert's syndrome; in case of Gilbert's syndrome, direct bilirubin > ULN
• INR > 1.2
• Any signs of liver cirrhosis decompensation, including gastrointestinal bleed within 6 months (24 weeks) prior to screening/enrollment visit
• Patient has moderate or severe renal impairment defined as eGFR CKD-EPI < 60 mL/min/1.73 m2, or patient has nephritis or nephrotic syndrome
• Any history or current evidence of HIV-1, HIV-2, HTLV 1, or HTLV-2 infection
• Any history or current evidence of hepatitis B infection
• Any history of hepatitis C infection, unless previous viral RNA assays in two samples, collected at least 6 months apart, are negative
• Positive QuantiFERON®-TB Gold tuberculosis test result
• Any concomitant disorder/condition - including hepatic disorders - or treatment possibly interfering with the conduct or evaluation of the study
• Any history of diabetes
• Pregnancy or breastfeeding
• Body Mass Index ≥ 35 kg/m2 Other protocol defined Inclusion/ Exclusion criteria may apply
Genetic: VTX-801
Wilson's Disease
UT Southwestern
Comparison of Chemotherapy Before and After Surgery Versus After Surgery Alone for the Treatment of Gallbladder Cancer
This phase II/III trial compares the effect of adding chemotherapy before and after surgery versus after surgery alone (usual treatment) in treating patients with stage II-III gallbladder cancer. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before surgery may make the tumor smaller; therefore, may reduce the extent of surgery. Additionally, it may make it easier for the surgeon to distinguish between normal and cancerous tissue. Giving chemotherapy after surgery may kill any remaining tumor cells. This study will determine whether giving chemotherapy before surgery increases the length of time before the cancer may return and whether it will increase a patient's life span compared to the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Porembka
155238
ALL
18 Years and over
PHASE2
NCT04559139
STU-2021-0113
Inclusion Criteria:
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Patient must have histologically-confirmed T2 or T3 gallbladder cancer discovered incidentally at the time of or following routine cholecystectomy for presumed benign disease
* NOTE: Patients with histologically-confirmed Tis, T1a, T1b, or T4 tumors are not eligible
* Patient must have undergone initial cholecystectomy within 12 weeks prior to randomization
* Patient must have the ability to understand and the willingness to sign a written informed consent document
* Leukocytes \>= 3,000/mcL (obtained =\< 28 days prior to randomization)
* Absolute neutrophil count \>= 1,500/mcL (obtained =\< 28 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained =\< 28 days prior to randomization)
* Total bilirubin =\< institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome are eligible if direct bilirubin \< 1.5 x ULN of the direct bilirubin (obtained =\< 28 days prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 28 days prior to randomization)
* Serum creatinine =\< institutional ULN OR creatinine clearance \>= 50 mL/min/1.73 m\^2 (Based on Cockcroft Gault estimation) (obtained =\< 28 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
Exclusion Criteria:
* Patient must not have any evidence of metastatic disease or inoperable loco-regional disease based on high-quality, preoperative, cross-sectional imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) of the chest, abdomen, and pelvis (C/A/P) obtained within 6 weeks prior to randomization, defined as
* No radiographic evidence of distant disease (M1 disease)
* No radiographic evidence of tumor invasion into multiple extrahepatic organs (T4 disease)
* No radiographic evidence of distant lymph node involvement (celiac, para-aortic, para-caval lymph nodes)
* No evidence of new-onset ascites
* Soft tissue thickening within or in direct communication with the gallbladder fossa, peri-portal lymph node involvement, involvement of one extrahepatic organ, and other disease within the confines of what constitutes 'localized resectable' disease are allowable
* Women must not be pregnant or breast feeding due to the potential harm to unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of child bearing potential must have a serum or urine pregnancy test to rule out pregnancy within 14 days prior to randomization. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must not expect to conceive or father children by being strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study DRUG: Cisplatin, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Lymphadenectomy, PROCEDURE: Partial Hepatectomy
Stage III Gallbladder Cancer AJCC v8, Stage IIIA Gallbladder Cancer AJCC v8, Stage IIIB Gallbladder Cancer AJCC v8, Stage II Gallbladder Cancer AJCC v8, Stage IIA Gallbladder Cancer AJCC v8, Stage IIB Gallbladder Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yazan Madanat
187698
ALL
18 Years to 75 Years old
PHASE3
NCT04530565
STU-2021-0640
Inclusion Criteria:
* ELIGIBILITY CRITERIA FOR PRE-REGISTRATION (TO STEP 0)
* Patient must be \>= 18 and =\< 75 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-3
* Patient must be newly diagnosed with B acute lymphoblastic leukemia (B-ALL) or is suspected to have acute lymphoblastic leukemia (ALL)
* Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the presence of BCR-ABL translocation must be confirmed centrally. Patients can be registered and begin step 1 therapy while awaiting central laboratory eligibility confirmation
* NOTE: Bone marrow aspirate and/or peripheral blood specimen must be submitted to the ECOG-American College of Radiology Imaging Network (ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to determine patient's eligibility for registration to Step 1 or confirm patient evaluability. Centrally fluorescence-activated cell sorting (FACS) analysis will be performed to determine B-ALL and to exclude acute myeloid leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status will be determined by fluorescent in situ hybridization (FISH). The ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of receipt of the specimen to the submitting institution. Bone marrow aspirate is to be from first pull (initial or re-direct). Specimens must contain sufficient blast cells. In cases where the bone marrow aspiration may be inadequate, or the bone marrow examination has already been performed prior to study consent and enrollment on Step 0, peripheral blood may be submitted, with recommendation that adequate circulating blasts are present (\> 10%). If a diagnosis of BCR-ABL positive B-ALL has already been established by local Clinical Laboratory Improvement Act (CLIA) certified laboratories, the patient may be registered to step 1 without waiting for central confirmation
* Patient must not have a diagnosis of BCR/ABL T-ALL
* Patient must not have received chemotherapy for B-ALL. Patients who received up to five days of therapy (hydroxyurea and/or steroids of any kind) with the aim to reduce disease burden prior to study registration to Step 1 are eligible
* Patient must not have unstable epilepsy that requires treatment
* Patients with lymphoid blast crisis chronic myeloid leukemia (CML) are not eligible
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 1
* Patient must have a diagnosis of Philadelphia chromosome positive (Ph+) ALL that has been determined locally and bone marrow and/or peripheral blood was sent and receipt confirmed for central confirmation or determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer Center
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of step 1 registration, while on study treatment, and until at least six months after the last dose of study treatment
* Total bilirubin =\< 3 mg/dL (patients with Gilbert's syndrome must have a total bilirubin =\< 5 mg/dL) (obtained =\< 28 days prior to step 1 registration)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X the institutional upper limit of normal (ULN) (obtained =\< 28 days prior to step 1 registration)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation) (obtained =\< 28 days prior to step 1 registration)
* Patients with acute organ dysfunction at step 1 registration, which may be attributed to leukemia can be registered regardless of lab results at presentation. Such patients will be allowed to register and can start Arm A steroid + TKI therapy but will only be allowed to proceed to step 2 randomization if the eligibility criteria outlined is met
* Patients who presented with no evidence of acute organ dysfunction but during step 0 experienced a rise in liver enzymes which investigator suspects to be a side effect of any of prescribed drugs, are allowed to be registered regardless of the level of liver enzymes. Step 2 randomization must be withheld until the eligibility criteria outline is met but no more than 14 days after concluding Arm A therapy
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load and if indicated, on treatment
* Patients with a prior malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patient must not have active concomitant malignancy. Patients on chronic hormonal therapy for breast or prostate cancer or patients treated with maintenance with targeted agents but are in remission with no evidence for the primary malignancies are eligible
* Patient must not have complaints of symptoms and/or have clinical and/or radiological signs that indicate an uncontrolled infection or any other concurrent medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients must be class 2B or better
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* NOTE: In situations due to insurance coverage issues and the pre-selected TKI is not immediately available, patients can receive dasatinib or imatinib during step 1. The investigator must re-specify dasatinib or ponatinib prior to step 2 randomization and from then on patients must receive the pre-selected TKI only
* ELIGIBILITY CRITERIA FOR RANDOMIZATION TO STEP 2
* Patient must have completed at least 7 and no more than 21 days of protocol-treatment on Arm A prior to step 2 randomization. (Days in which arm A therapy was withheld for any reason are not counted)
* NOTE: First day of steroids prescription after registration will be considered as the first day of study therapy. The selected TKI must be initiated prior to randomization
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional upper limit of normal (ULN)
* AST(SGOT)/ ALT(SGPT) =\< 2 X the institutional upper limit of normal (ULN)
* Estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive.
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70, intended chemotherapy regimen must have been determined prior to randomization
* Patient must not have active central nervous system (CNS) involvement by leukemic blasts. Patients with signs of CNS involvement at presentation are eligible for randomization if clearance of blasts from the cerebrospinal fluid (CSF) is demonstrated
* Patients must have resolved any serious infectious complications related to therapy
* Any significant medical complications related to therapy must have resolved
* ELIGIBILITY CRITERIA FOR REGISTRATION TO STEP 3 (RE-INDUCTION)
* Institution has received centralized MRD results confirming positive status
* Patients who presented with acute organ dysfunction within 2 weeks of registration to step 1 must have total bilirubin =\< 2 X institutional ULN
* Patients who presented with acute organ dysfunction must have AST (SGOT)/ALT (SGPT) =\< 2 X institutional upper limit of normal (ULN)
* Patients who presented with acute organ dysfunction must have an estimated creatinine clearance \> 45 mL/min (based on Cockcroft-Gault equation)
* Investigators must confirm which TKI patient is to receive
* NOTE: Patients with known T315I mutation status should receive ponatinib treatment
* For patients under age 70 and previously assigned to Arm C, intended chemotherapy regimen must have been determined
* Step 3 (Re-Induction): Patients must have resolved any serious infectious complications related to therapy
* Step 3 (Re-Induction): Any significant medical complications related to therapy must have resolved PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration and Biopsy, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Dexamethasone, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Echocardiography, PROCEDURE: Electrocardiography, PROCEDURE: Lumbar Puncture, DRUG: Mesna, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Ponatinib Hydrochloride, DRUG: Prednisone, DRUG: Vincristine Sulfate
B Acute Lymphoblastic Leukemia With t(9,22)(q34.1,q11.2), BCR-ABL1
UT Southwestern
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Advanced Liver Cancers (Morpheus-Liver)
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer. Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
171069
ALL
18 Years and over
PHASE1
NCT04524871
STU-2020-1312
Inclusion Criteria:
Stage 1
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
* Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of
* Liver Diseases criteria in cirrhotic patients
* Child-Pugh class A within 7 days prior to randomization
* Disease that is not amenable to curative surgical and/or locoregional therapies
* No prior systemic treatment for HCC
* Life expectancy \>= 3 months
* Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
Stage 1 and Stage 2
* Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
* Adequate hematologic and end-organ function within 7 days prior to initiation of study treatment
* Documented virology status of hepatitis, as confirmed by screening tests for hepatitis B virus - (HBV) and hepatitis C virus (HCV)
* Negative HIV test at screening
* For women of childbearing potential: agreement to remain abstinent or use contraception and for men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm
Stage 2
* ECOG Performance Status of 0, 1, or 2
* Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab or RO7247669 or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
* Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible)
Exclusion Criteria:
Stage 1
* Prior treatment with CD137 agonists or immune checkpoint blockade therapies or inhibitors targeting HIF2a
* Treatment with investigational therapy within 28 days prior to initiation of study
* Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding
* Prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study
* AEs from prior anti-cancer therapy that have not resolved to Grade \<= 1 or better, with the exception of alopecia of any grade
* Inadequately controlled hypertension
* History of hypertensive crisis or hypertensive encephalopathy
* Significant vascular disease
* History of hemoptysis within 1 month prior to initiation of study
* Evidence of bleeding diathesis or significant coagulopathy
* Current or recent use of asprin (\>325 mg/day) or treatment with clopidogrel, dipyramidole, ticlopidine, or cilostazol
* Current or recent use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose
* Core biopsy or other minor surgical procedure within 3 days prior to initiation of study
* History of abdominal or tracheoesophageal fistula, GI perforation, or intra-abdominal abscess, intestinal obstruction and/or clinical signs/symptoms of GI obstruction
* Evidence of abdominal free air not explained by paracentesis or recent surgery
* Serious, non-healing/dehiscing wound, active ulcer, or untreated bone fracture
* Grade \>=2 proteinuria
* Metastatic disease involving major airways/blood vessels, or centrally located mediastinal tumor masses of large volume
* History of clinically significant intra-abdominal inflammatory process
* Radiotherapy within 28 days or abdominal/pelvic radiotherapy within 60 days prior to initiation of study with the exception of palliative radiotherapy to bone lesions within 7 days prior to initiation of study
* Major surgery, open biopsy, or significant traumatic injury within 28 days prior to initiation of study; or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study; or anticipation of need for major surgery during study or non-recovery from side effects of any such procedure
* Chronic daily treatment with NSAID
* Eligible only for control arm
Stage 1 and 2
* Fibrolamellar or sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
* History of hepatic encephalopathy
* Moderate or severe ascites
* HBV and HCV coinfection
* Symptomatic, untreated, or actively progressing CNS metastases
* History of leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
* Uncontrolled or symptomatic hypercalcemia
* Active or history of autoimmune disease or immune deficiency
* History of IPF, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
* Active TB
* Significant CV disease within 3 months prior to initiation of study, unstable arrhythmia, or unstable angina
* Major surgery, other than for diagnosis, within 4 weeks prior to initiation of study, or anticipated major surgery during study
* History of malignancy other than HCC within 5 years prior to screening
* Severe infection within 4 weeks prior to initiation of study
* Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study
* Prior allogeneic stem cell or solid organ transplantation
* Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known allergy or hypersensitivity to any of the study drugs or any of their excipients Treatment with systemic immunostimulatory, immunosuppressive agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study
* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
* Patients entering Stage 2: immunotherapy-related adverse events that have not resolved to Grade 1 or better or to baseline at time of consent DRUG: Atezolizumab, DRUG: Bevacizumab 15 mg/kg, DRUG: Tiragolumab, DRUG: Tocilizumab, DRUG: TPST-1120, DRUG: Tobemstomig 2100 mg, DRUG: Bevacizumab 10 mg/kg, DRUG: Tobemstomig 600 mg, DRUG: Tobemstomig 1200 mg dose, DRUG: ADG126, DRUG: IO-108, DRUG: NKT2152
Advanced Liver Cancers
UT Southwestern
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial (PROBE)
This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 3
NCT04510597
STU-2021-0266
Inclusion Criteria:
• STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
• STEP 1 REGISTRATION: Participants must have primary tumor in place
• STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
• Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast Scans must be performed within the following timeframes:
• Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
• Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
• STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
• STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
• STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
• STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
• STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
• STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
• CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
• CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2 • STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
• Stable disease
• Partial response
• The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
• STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
• STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
• STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
• 2 infusions of nivolumab + 1 infusion of ipilimumab
• 2 infusions of pembrolizumab
• 2 infusions of avelumab
• STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
• STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
• STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
• STEP 2 REGISTRATION: Total bilirubin =< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
• STEP 2 REGISTRATION: Serum creatinine =< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
Exclusion Criteria:
• STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
• Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
• Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
• Treatment naive participants must not have received any pre-randomization treatment.
• Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
• 4 infusions of nivolumab
• 4 infusions of ipilimumab
• 4 infusions of pembrolizumab
• 7 infusions of avelumab
• STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
• Treatment naive participants must not have received any immunotherapy within a year of registration
• Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
• STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
• STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
• STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
• STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
• STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
• STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
Procedure: Cytoreductive Nephrectomy, Drug: Active Comparator
Metastatic Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
A Study of the Natural History of Participants With LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, and LGMD2A/R1 ≥ 4 Years of Age, Who Are Managed in Routine Clinical Practice
This study will follow participants who are screened and confirmed with a genetic diagnosis of Limb-girdle muscular dystrophy type 2E (LGMD2E/R4), Limb-girdle muscular dystrophy type 2D (LGMD2D/R3), Limb-girdle muscular dystrophy type 2C (LGMD2C/R5), or Limb-girdle muscular dystrophy type 2A (LGMD2A/R1). These enrolled participants will be followed to evaluate mobility and pulmonary function for up to 3 years after enrollment. Additional participant data will be collected from the time the individual began experiencing LGMD symptoms to the present.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alyssa.Boudreau@UTSouthwestern.edu
Kaitlin Batley
162753
All
4 Years and over
NCT04475926
STU-2020-0865
Inclusion Criteria:
• Male or female participant ≥ 4 years of age with confirmed genetic diagnosis of LGMD2E/R4, LGMD2D/R3, LGMD2C/R5, or LGMD2A/R1.
Exclusion Criteria:
• Demonstrates cognitive delay or impairment that could confound motor development, in the opinion of the Investigator.
• Has a medical condition, in the opinion of the Investigator, that might compromise participants ability to comply with study requirements.
• Is participating in other interventional study(ies) at the time of enrollment in this study.
Limb-girdle Muscular Dystrophy
North Star Assessment for Dysferlinopathy (NSAD), Performance of Upper Limb (PUL), Pulmonary function tests (PFTs), Ambulatory, Non-Ambulatory, Limb-girdle, LGMD, sarcoglycanopathy, β -sarcoglycan, Muscular Dystrophy, α -sarcoglycan, γ -sarcoglycan, LGMD-2D/R3, LGMD-2E/R4, LGMD-2C/R5, LGMD2A/R1, Clinical Outcomes Assessment
UT Southwestern; Children’s Health
T-DM1 and Tucatinib Compared With T-DM1 Alone in Preventing Relapses in People With High Risk HER2-Positive Breast Cancer, the CompassHER2 RD Trial
This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in preventing breast cancer from coming back (relapsing) in patients with high risk, HER2 positive breast cancer. T-DM1 is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called DM1. Trastuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors, and delivers DM1 to kill them. Tucatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving T-DM1 and tucatinib may work better in preventing breast cancer from relapsing in patients with HER2 positive breast cancer compared to T-DM1 alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Nisha Unni
148963
All
18 Years and over
Phase 3
NCT04457596
STU-2021-0101
Inclusion Criteria:
• HER2-positive status will be based on pretreatment biopsy material and defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) according to current American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines. Central testing is not required * Known hormone receptor (HR) status as defined by ASCO/CAP guidelines (based on pretreatment biopsy material). Hormone receptor positive status can be determined by either known positive estrogen receptor (ER) or known positive progesterone receptor (PR) status; hormone receptor negative status must be determined by both known negative ER and known negative PR
• Patients with clinical stage T1-4, N0-3 disease at presentation and residual invasive disease postoperatively as defined above are eligible. (Note: Patients with T1a/bN0 tumors are not eligible at initial breast cancer diagnosis are not eligible)
• Patients with residual HR-negative, HER2 positive (+) disease in the breast and/or lymph nodes per the surgical pathology report are eligible; however, patients with HR+ HER2+ cancers must have node-positive residual disease per the surgical pathology report in order to qualify for the study. The presence of residual invasive disease in the breast is not mandatory for these patients
• Patients with weakly ER-positive (1-10%) breast cancer (based on the pretreatment core biopsy) are eligible even if they have node-negative disease per the surgical pathology report
• The residual disease tissue (breast and/or lymph nodes) is not required to be HER2-positive, as eligibility for NCI-2020-03770 (A011801) is based on a positive HER2 status at the time of the initial breast cancer diagnosis * Note: The presence of micrometastases in lymph nodes after preoperative therapy counts as residual disease, whereas the presence of isolated tumor cells does not
• Patients with synchronous bilateral invasive disease are eligible provided both lesions were confirmed to be HER2-positive, and at least one of the lesions meets the criteria outlined above. Multifocal disease is allowed, as long as the largest biopsied breast tumor was HER2-positive
• Patients must have received neoadjuvant chemotherapy with one of the following regimens: docetaxel/trastuzumab/pertuzumab (THP), paclitaxel/methotrexate/cisplatin (TMP), doxorubicin/cyclophosphamide/paclitaxel/trastuzumab/pertuzumab (AC-TH(P)); docetaxel/carboplatin/trastuzumab/pertuzumab (TCH(P)); fluorouracil/doxorubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FAC-TH(P)), or fluorouracil/epirubicin/cyclophosphamide-docetaxel/trastuzumab/pertuzumab (FEC-TH(P)). Note: apart from TCHP, where T is docetaxel, treatment with docetaxel or paclitaxel is acceptable
• Prior receipt of T-DM1 in the neoadjuvant setting is not allowed.
• Prior treatment must have consisted of >= 6 cycles of chemotherapy and HER2-directed therapy, with a total duration of >= 12 weeks, including at least 9 weeks of preoperative taxane and trastuzumab with or without pertuzumab (or Food and Drug Administration [FDA]-approved biosimilars). Patients who have received at least 9 weeks of preoperative taxane, pertuzumab and margetuximab are also eligible if they received >= 6 cycles of systemic therapy prior to enrollment. Note: Patients who complete at least nine of a planned twelve doses of weekly paclitaxel, or three of a planned four doses of docetaxel, but discontinue prematurely due to toxicity are eligible. Patients receiving dose-dense chemotherapy regimens are also eligible. Prior use of nab-paclitaxel (Abraxane) instead of paclitaxel or docetaxel is permitted. Prior use of subcutaneous trastuzumab (Hylecta) and subcutaneous trastuzumab and pertuzumab (Phesgo) is also allowed.
• Patients who received neoadjuvant systemic therapy which included experimental HER2-targeted therapy/therapies are potentially eligible, as long as the investigational agent was not a HER2-targeted antibody-drug conjugate (e.g. T-DM1, DS-8201a [trastuzumab deruxtecan]) or a HER2 targeted tyrosine kinase inhibitor (TKI) (e.g. tucatinib, lapatinib, neratinib).
• Patients may have received =< 1 cycles of T-DM1 in the adjuvant setting. Note: These patients will be randomized to receive a further 14 cycles of T-DM1 and tucatinib/placebo as tolerated. The most recent cycle of T-DM1 should have been administered =< 5 weeks prior to registration * Note: Both of the following two criteria need to be met for the patient to be eligible for this study
• An interval of no more than 12 weeks between the completion date of the last definitive treatment (e.g. postoperative chemotherapy or radiation, or if neither given, breast surgical date) and the date of registration. Concurrent radiation therapy is permitted while receiving study treatment
• Patients must be registered on study within =< 180 days of the date of the most recent definitive breast cancer surgery (not including reconstructive surgery)
• All systemic chemotherapy should have been completed preoperatively unless participating in EA1181 (CompassHER2 pathologic complete response [pCR]) or the BIG DECRESCENDO Trial (which is very similar to CompassHER2 pCR in terms of study design, drugs, and eligibility). However, patients who received 4 cycles of neoadjuvant THP off study can receive a further 2-4 cycles of chemotherapy postoperatively to meet eligibility for A011801. Patients who participated in EA1181 or MA41 and proceeded to surgery immediately after the de-escalated trial regimen must receive postoperative chemotherapy to complete a total of >= 6 cycles of systemic treatment prior to enrollment on A011801, as outlined above (e.g. 4 cycles pre-operatively, and 2 cycles post-operatively). The postoperative chemotherapy regimen prescribed is at the discretion of the treating oncologist (i.e. 2-4 cycles AC or THP, other). Continuation of trastuzumab + pertuzumab (HP) pre- or post-operatively as maintenance therapy (while awaiting a surgical date or an official pathology report) is allowed for all study participants
• Toxicities related to prior systemic treatment should have resolved or be at baseline, apart from alopecia and peripheral neuropathy =< grade 1
• Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as follows:
• Breast surgery: total mastectomy with no gross residual disease at the margin of resection, or breast-conserving surgery with histologically negative margins of excision
• For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of invasive tumor and ductal carcinoma in situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection
• Lymph node surgery ** The axilla needs to be evaluated with either sentinel node biopsy or axillary lymph node dissection. If patients have a sentinel lymph node biopsy and sentinel nodes are negative, no further axillary treatment is necessary. If patients have isolated tumor cells (ITCs) in the setting of residual breast disease, at least one of the following is required: axillary lymph node dissection (ALND) or planned nodal irradiation. If patients have micro- or macro-metastatic nodal disease, ALND and planned nodal irradiation are required. Of note, co-enrollment on Alliance A011202 is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Hemoglobin >= 8 g/dL (Note: packed red blood cells [PRBC] transfusion is not permitted to achieve eligibility)
• Platelet count >= 100,000/mm^3
• Creatinine =< 1.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.0 x upper limit of normal (ULN) or direct bilirubin within the institutional normal range for patients with Gilbert's syndrome
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Screening left ventricular ejection fraction (LVEF) >= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute percentage points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55% after completion of neoadjuvant chemotherapy. Note: LVEF assessment may be repeated once up to 3 weeks following the initial screening assessment to assess eligibility
Exclusion Criteria:
• No adjuvant treatment with any anti-cancer investigational drug within 28 days prior to registration
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required
• Patients with known active and/or untreated hepatitis B or hepatitis C or chronic liver disease are ineligible. Patients with a diagnosis of hepatitis B or C that has been treated and cleared and normal liver function are eligible to participate in the study if the other eligibility parameters are met
• Stage IV (metastatic) breast cancer
• History of any prior (ipsi- or contralateral) invasive breast cancer within 3 years of registration
• Patients with ER+ HER2+ residual invasive disease that is lymph node-negative per the surgical pathology report
• Evidence of recurrent disease following preoperative therapy and surgery
• Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons (e.g., connective tissue disorder or prior ipsilateral breast radiation)
• History of exposure to the following cumulative doses of anthracyclines: doxorubicin > 240 mg/m^2; epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m^2. For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m^2
• Cardiopulmonary dysfunction as defined by any of the following:
• History of National Cancer Institute (NCI) CTCAE version (v) 5.0 grade >= 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) criteria class >= II
• Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease
• High-risk uncontrolled arrhythmias: i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade atrioventricular block (AV)-block (second degree AV-block type 2 [Mobitz 2] or third degree AV-block)
• Significant symptoms (grade >= 2) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia while or since receiving preoperative therapy
• History of a decrease in left ventricular ejection fraction (LVEF) to < 40% with prior trastuzumab treatment (e.g., during preoperative therapy)
• Uncontrolled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)
• Current severe, uncontrolled systemic disease
• Major surgical procedure unrelated to breast cancer or significant traumatic injury within 28 days prior to registration or anticipation of the need for major surgery during the course of study treatment
• History of intolerance, including grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product
• Peripheral neuropathy of any etiology that exceeds grade 1
• Assessment by the investigator as being unable or unwilling to comply with the requirements of the protocol
• Use of a strong CYP3A4 or CYP2C8 inhibitor within 2 weeks, or use of a strong CYP3A4 or CYP2C8 inducer within 5 days prior to registration is prohibited.
• Please note that use of sensitive CYP3A substrates should be avoided two weeks before registration and during study treatment. Additionally, CYP3A4 or CYP2C8 inducers are prohibited as concomitant medications within 5 days following discontinuation of tucatinib treatment. Patients who require medications that are known to be sensitive substrates of CYP3A4 with a narrow therapeutic window should be excluded.
Biological: Trastuzumab Emtansine, Drug: Placebo Administration, Drug: Tucatinib, Other: Questionnaire Administration, Other: Quality-of-Life Assessment
Invasive Breast Carcinoma, HER2 Positive Breast Carcinoma, Multifocal Breast Carcinoma, Synchronous Bilateral Breast Carcinoma, Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Anatomic Stage IIB Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage IIA Breast Cancer AJCC v8, Prognostic Stage IIB Breast Cancer AJCC v8, Prognostic Stage IIIA Breast Cancer AJCC v8, Breast - Female, Breast - Male, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IIIB Breast Cancer AJCC v8, Anatomic Stage IIIC Breast Cancer AJCC v8, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage IA Breast Cancer AJCC v8, Prognostic Stage IB Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IIIB Breast Cancer AJCC v8, Prognostic Stage IIIC Breast Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Study to Continue Treatment With Darolutamide in Patients Who Have Been Participating in Previous Darolutamide Studies Supported by Bayer
studyfinder@utsouthwestern.edu
MALE
18 Years to old
PHASE3
NCT04464226
Inclusion Criteria:
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
* Participants enrolled in any Bayer-sponsored darolutamide feeder study at the time of study closure or primary completion, who are currently receiving darolutamide and are experiencing clinical benefit from treatment.
* Participants who have not met any treatment discontinuation criteria in the feeder study protocol.
* Willingness to continue practicing acceptable methods of birth control during the study.
Exclusion Criteria:
* Participant is unable to comply with the requirements of the study.
* Negative benefit/ risk ratio as determined by the investigator.
* Meet any criteria for treatment discontinuation of the feeder study the participant is coming from. DRUG: Darolutamide (Nubeqa, BAY1841788)
Cancer
Roll-Over Study
Cerebellar tDCS in Children With Autism Spectrum Disorder
The purpose of this research study is to investigate whether tDCS to the cerebellum (specifically, the right crus I/II area of the cerebellum) of children and young adults with autism spectrum disorders (ASD) is safe and to examine its effects on some of the symptoms of ASD, such as repetitive behaviors and hyperactivity.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Haley.Walker@UTSouthwestern.edu
Peter Tsai
153860
All
4 Years to 17 Years old
N/A
NCT04446442
STU-2022-0689
Inclusion Criteria:
• 4-17 years old
• Diagnosed with ASD and ADOS-2
• IQ Score no less than 70 (1.5 Standard Deviations below the mean)
• Language Level (Speech consists of, at minimum, flexible, spontaneous, simple, sentences)
Exclusion Criteria:
• Brain implants, metal implants, pacemakers, or biomedical devices
• Diagnosis of epilepsy
• Hearing or visual impairments
• History of brain injury
• Known brain abnormalities not associated with ASD
Device: tDCS
Autism Spectrum Disorder
UT Southwestern; Children’s Health
Cryopreserved Human Umbilical Cord (TTAX01) for Late Stage, Complex Non-healing Diabetic Foot Ulcers (AMBULATE DFU II)
It is hypothesized that application at 4-week or greater intervals of the human placental umbilical cord tissue TTAX01 to the surface of a well debrided, complex diabetic foot ulcer (DFU) will, with concomitant management of infection, result in a higher rate of wounds showing complete healing within 25 weeks of initiating therapy, compared with standard care alone. This second confirmatory Phase 3 study examines a population of diabetic foot ulcer patients having adequate perfusion, with or without neuropathy, and a high suspicion of associated osteomyelitis in a complex, high grade wound.
Call 214-648-5005
studyfinder@utsouthwestern.edu, LARRY.LAVERY@UTSouthwestern.edu
Lawrence Lavery
116716
ALL
18 Years and over
PHASE3
NCT04450693
STU-2020-1367
Inclusion Criteria:
* The subject has signed the informed consent form
* The subject is male or female, at least 18 years of age inclusive at the date of Screening
* The subject has confirmed diagnosis of Type I or Type II diabetes
* The subject's index ulcer is located on the plantar surface, inter digital, heel, lateral or medial surface of the foot
* The subject has an index ulcer with visible margins having an area ≤ 12.0 cm2 when measured by the electronic measuring device at Screening
* The subject's index ulcer extends beyond the dermis, into subcutaneous tissue with evidence of exposed bone, tendon, muscle and/or joint capsule
* The subject presents with history, signs or symptoms leading to a clinical suspicion of osteomyelitis in the opinion of the Investigator supported by positive Probe to Bone (PTB) and any of the following: radiographic (X-ray, Magnetic Resonance Imaging (MRI), or bone scan) or evidence of bone necrosis
* The subject has an Ankle-Brachial Index ≥ 0.7 to ≤ 1.3 or TcPO2 ≥ 40 mmHg on the dorsum of the affected foot, or Great Toe Pressure ≥ 50 mmHg
* The subject is under the care of a physician for the management of Diabetes Mellitus
* The subject is willing to return for all mandatory visits as defined in the protocol
* The subject is willing to follow the instructions of the trial Investigator
Exclusion Criteria:
* The subject's index ulcer is primarily located on the dorsal surface of the foot
* The subject's index ulcer can be addressed by primary closure through the completion of the initial or staged surgical procedure
* The subject has a contralateral major amputation of the lower extremity
* The subject has a glycated hemoglobin A1c (HbA1c) level of \> 12% †
* The subject has been on oral steroid use of \> 7.5 mg daily for greater than seven (7) consecutive days in 30 days before Screening
* The subject has been on parenteral corticosteroids, or any cytotoxic agents for seven consecutive days in the period of 30 days before Screening
* The subject is currently taking the type 2 diabetes medicine canagliflozin (Invokana™, Invokamet™, Invokamet XR™)
* The subject has malignancy or a history of cancer, other than non-melanoma skin cancer, in five years before Screening
* The subject is pregnant
* The subject is a nursing mother
* The subject is a woman of child-bearing potential who is unwilling to avoid pregnancy or use an appropriate form of birth control (adequate birth control methods are defined as: topical, oral, implantable, or injectable contraceptives; spermicide in conjunction with a barrier such as a condom or diaphragm; intrauterine contraceptive device; or surgical sterilization of partner).
* The subject is unable to sustain off-loading as defined by the protocol
* The subject has an allergy to primary or secondary dressing materials used in this trial
* The subject has an allergy to glycerol
* The subject's index ulcer is over an acute Charcot deformity
* The subject has had previous use of NEOX®, CLARIX®, or TTAX01 applied to the index ulcer
* Per Investigator's discretion the subject is not appropriate for inclusion in the trial, e.g., undergoing surgical treatments listed in the protocol or the subject currently has sepsis, i.e., life-threatening organ dysfunction caused by a dysregulated host response to infection BIOLOGICAL: TTAX01, OTHER: Standard care
Diabetic Foot Infection, Non-healing Wound, Non-healing Diabetic Foot Ulcer
UT Southwestern; Parkland Health & Hospital System
EA2176: Phase 3 Clinical Trial of Carboplatin and Paclitaxel +/- Nivolumab in Metastatic Anal Cancer Patients
This phase 3 trial compares the addition of nivolumab to chemotherapy (carboplatin and paclitaxel) versus usual treatment (chemotherapy alone) for the treatment of anal cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab together with carboplatin and paclitaxel may help doctors find out if the treatment is better or the same as the usual approach.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
ALL
18 Years and over
PHASE3
NCT04444921
STU-2021-0016
Inclusion Criteria:
* Patient must have inoperable, recurrent, or metastatic disease not amenable to curative therapy
* Patient must have histological or cytological confirmation of anal squamous cell carcinoma (includes basaloid and cloacogenic lesions) from the primary tumor or a newly diagnosed recurrent/metastatic lesion
* Patient must be \>= 18 years of age
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 0-1
* Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 and based on radiologic assessment performed \< 4 weeks prior to randomization
* Patient receiving palliative (limited-field) radiation therapy is allowed, as long as the lesion treated for palliation is not a target lesion and is \> 7 days from completion from palliative radiation
* Patients with brain metastasis are eligible if patient is asymptomatic and if treatment ended \> 3 months prior to randomization. Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression within 4 weeks prior to randomization
* Absolute neutrophil count \>= 1,500/mcL (obtained \< 14 days prior to randomization)
* Platelets \>= 100,000/mcL (obtained \< 14 days prior to randomization)
* Hemoglobin (Hb) \>= 9 g/dL for males and \>= 9 g/dL for females (obtained \< 14 days prior to randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained \< 14 days prior to randomization)
* Aspartate transaminase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\]) /alanine transferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN (obtained \< 14 days prior to randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula) (obtained \< 14 days prior to randomization)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (ART) with CD4 count \>= 200 or have a CD4 count \< 200 but an undetectable viral load are eligible
* All HIV+ patients should be under the care of an infectious diseases specialist. If a relationship with an infectious diseases specialist is not established, an infectious disease specialist should be consulted. Records of all viral counts and peripheral T-cell counts should be documented in order to follow these values over the course of treatment
* All patients must be willing to undergo testing for HIV testing if not tested within the past 12 months
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable or on suppressive therapy (if indicated)
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better. Patients with a history of congestive heart failure (CHF) or who are at risk because of underlying cardiovascular disease or exposure to cardiotoxic drugs must be willing to undergo evaluation of cardiac function including electrocardiogram (EKG) and echocardiogram (ECHO) as clinically indicated
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patients must agree to not receive live vaccines while on this study
Exclusion Criteria:
* Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females of childbearing potential must have a blood test or urine study with a minimum sensitivity of 25 IU/L or equivalent units of Bacille Calmette-Guerin (BCG), within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Women of childbearing potential and sexually active males must not expect to conceive or father children by using accepted and effective method(s) of contraception or to abstain from sexual intercourse for at least one week prior to the start of treatment, and continue for 5 months after the last dose of protocol treatment for women of childbearing potential and 7 months after the last dose of protocol treatment for males who are sexually active with women of childbearing potential (WOCBP)
* Patient must not have had previous use of systemic chemotherapy or other investigational drugs for the treatment of inoperable recurrent or metastatic anal cancer (previous use of radiotherapy or chemoradiotherapy in this setting is not an exclusion criterion if: 1) non-irradiated target tumor lesions are present at randomization for the purpose of tumor response assessment or 2) in the absence of non-irradiated target tumor lesions, progression of the irradiated tumor lesions according to the RECIST criteria version 1.1 is documented)
* Patient must not have current or recent (within 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study
* Patient must not have had prior immunotherapy
* Patient must not have a history of known hypersensitivity reaction to any platinum or taxane-based chemotherapy or monoclonal antibody
* Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater). 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, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome. Patients with any of these are ineligible because of the risk of recurrence or exacerbation of autoimmune disease
* Patient must not have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \< 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
* Patient must not have had major surgery performed =\< 28 days prior to randomization
* Patient must not have a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computed tomography (CT) scan
* Patient must not have a serious active infection requiring IV antibiotics at time of randomization
* Patient must not have other primary malignancy within the last 3 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer, or any other cancer from which the patient has been disease-free for at least 3 years
* Patient must not have known peripheral neuropathy \> grade 1 at the time of randomization (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible) DRUG: Carboplatin, BIOLOGICAL: Nivolumab, DRUG: Paclitaxel
Anal Canal Cloacogenic Carcinoma, Stage III Anal Cancer AJCC v8, Metastatic Anal Squamous Cell Carcinoma, Recurrent Anal Squamous Cell Carcinoma, Stage IV Anal Cancer AJCC v8, Unresectable Anal Squamous Cell Carcinoma, Anal Basaloid Squamous Cell Carcinoma
UT Southwestern; Parkland Health & Hospital System
A Study of Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) With or Without Selinexor in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma
The purpose of this Phase 2/3 study is to evaluate efficacy and safety of the combination of selinexor and R-GDP (SR-GDP) in patients with RR DLBCL who are not intended to receive hematopoetic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR-T) therapy. This study consists of 3 arms each in Phase 2 and 3. Phase 2 portion of the study will assess the two doses of selinexor (40 milligram [mg] or 60 mg) in combination with R-GDP, for up to 6 cycles (21-day per cycle), followed by 60 mg selinexor single agent continuous therapy for those who have reached a partial or complete response. Phase 3 portion of the study will evaluate the selected dose of SR-GDP (identified in Phase 2) versus standard R-GDP + matching placebo, for up to 6 cycles (21-day per cycle), followed by placebo or 60 mg selinexor single agent continuous therapy for those who have reached partial or complete response.
studyfinder@utsouthwestern.edu
ALL
18 Years and over
PHASE2
NCT04442022
Inclusion Criteria:
* Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patient with high-grade lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements are eligible (only for Phase 2). (Documentation to be provided).
* Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen.
* Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy.
* Maintenance therapy will not be counted as a separate line of systemic therapy.
* Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy.
* Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (\>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi \>1 cm (per the Lugano Criteria 2014). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5.
* Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15 percent \[%\] of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician.
* Adequate bone marrow function at screening, defined as:
* Absolute neutrophil count (ANC) ≥1\*10\^9 per liter (/L).
* Platelet count ≥100\*10\^9/L (without platelet transfusion less than \[\<\] 14 days prior to Cycle 1 Day 1 \[C1D1\]).
* Hemoglobin ≥8.5 gram per deciliter (g/dL) (without red blood cell transfusion \<14 days prior to C1D1).
* Circulating lymphocytes less than or equal to (≤) 50\*10\^9/L.
* Adequate liver and kidney function, defined as:
* Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5\*upper limit of normal (ULN), or ≤5\*ULN in cases with known lymphoma involvement in the liver.
* Serum total bilirubin ≤2\*ULN, or ≤5\*ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver.
* Calculated creatinine clearance (CrCl) ≥30 milliliter per minute (mL/min) based on Cockcroft-Gault formula.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* An estimated life expectancy of \>3 months at Screening.
* Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment, will be allowed in the study.
* Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment
* Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with Non-Childbearing potential: Age \>50 years and naturally amenorrhoeic for \>1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy).
* Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.
Exclusion Criteria:
* DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite lymphoma (Hodgkin's lymphoma + non-Hodgkin's lymphoma \[NHL\]), DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma.
* Previous treatment with selinexor or other XPO1 inhibitors.
* Contraindication to any drug contained in the combination therapy regimen (SR-GDP).
* Known active central nervous system or meningeal involvement by DLBCL at time of Screening.
* Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) \<21 days prior to C1D1 (prednisone \<30 mg or equivalent is permitted; palliative radiation is permitted only if on non-target lesions).
* Any AE, by C1D1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events \[CTCAE\], v.5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (as specified in the inclusion criteria) and alopecia.
* Major surgery \<14 days of Cycle 1 Day 1.
* Hematopoietic stem cell transplantation/CAR-T therapy as follows:
* Autologous stem cell transplant (SCT) \<100 days or allogeneic-SCT \<180 days prior to C1D1
* Active graft-versus-host disease (GVHD) after allogeneic SCT (or cannot discontinue GVHD treatment or prophylaxis)
* CAR-T cell infusion \<90 days prior to Cycle 1
* Neuropathy Grade ≥2 (CTCAE, v.5.0).
* Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or being compliant with the study procedures.
* Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
* Patient with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections:
* Patient with active HBV are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 International units (IU)/mL prior to first dose of study treatment.
* Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard.
* Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year.
* Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal (GI) disease or dysfunction that could interfere with absorption of study treatment.
* Breastfeeding or pregnant women.
* Inability or unwillingness to sign an informed consent form (ICF).
* In the opinion of the Investigator, patient who are significantly below their ideal body weight.
* Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment. DRUG: Selinexor (combination therapy), DRUG: Selinexor (combination therapy), DRUG: Selinexor (combination therapy), DRUG: Placebo matching for Selinexor (combination therapy), DRUG: Rituximab (combination therapy), DRUG: Rituximab (combination therapy), DRUG: Gemcitabine (combination therapy), DRUG: Dexamethasone (combination therapy), DRUG: Cisplatin (combination therapy), DRUG: Selinexor (continuous therapy), DRUG: Placebo matching for Selinexor (continuous therapy)
Relapsed/Refractory Diffuse Large B-cell Lymphoma
Relapsed/Refractory DLBCL, Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP), Selinexor, Karyopharm, KCP-330, XPOVIO, DLBCL, XPORT-DLBCL-030, R-GDP
Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
The overall goal of the study is to determine if treatment of a Major Depressive Disorder (MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD is present in 25% of CKD patients and independently associated with progression to End-Stage Kidney Disease, hospitalization, and death. Depression is also associated with lower quality of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However, evidence for efficacy and tolerability of commonly-used antidepressant medications or nonpharmacologic treatments are limited in CKD patients. Our group was the first to conduct a double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor (SSRI), was no more efficacious than placebo for improving depressive symptoms. It becomes imperative to test novel strategies to treat MDD in CKD. We propose to compare with a control group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters); and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim 1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with non-dialysis CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a control group of Clinical Management plus placebo. We hypothesize that either approach vs. control will result in a minimal clinically important difference of 2 points improvement in depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1) single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs. control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d. overall functioning. A clinical trial is urgently needed to address the evidence gap that exists for MDD treatment in CKD patients.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ana.Arroyo@UTSouthwestern.edu
Meredith McAdams
181699
All
18 Years and over
Phase 2
NCT04422652
STU-2020-0046
Inclusion Criteria:
• Male or female adults aged 18 years or greater. There will be no upper age limit.
• Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula.
• Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria
• Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.
• Able to understand and sign informed consent after the nature of the study has been fully explained
• Kidney transplant patients that are at least 6 month post-transplantation (3 months post-transplant, with at least another 3 months to confirm eGFR <45)
Exclusion Criteria:
• Unable to understand or give informed consent.
• Unwilling or unable to participate in the protocol or comply with any of its components
• Receiving chronic dialysis
• Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal
• Terminal chronic obstructive pulmonary disease or cancer
• Presence of seizure disorder
• Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants
• Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.
• Use of medications known to cause QT prolongation on EKG
• Ongoing use of antidepressant medications for depression treatment
• Past treatment failure on bupropion
• Initiation of depression-focused psychotherapy in the 3 months prior to study entry
• Active alcohol or substance abuse or dependence that requires acute detoxification at study entry
• Present or past psychosis or Bipolar I or II disorder
• Dementia or a Mini-Mental State Examination score <23
• Active suicidal intent
• Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception
Drug: Bupropion, Behavioral: Behavioral activation therapy, Drug: Placebo, Other: Clinical Management
Major Depressive Disorder, Chronic Kidney Diseases, Kidney
UT Southwestern; Parkland Health & Hospital System
Registry of Patients With Brain Tumors Treated With STaRT (GammaTiles)
The objectives of this registry study are to evaluate real-world clinical outcomes and patient reported outcomes that measure the effectiveness and safety of STaRT.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Toral Patel
55706
ALL
Not specified
NCT04427384
STU-2020-1206
Inclusion Criteria:
• Patients who undergo maximum safe resection of intracranial neoplasm(s) AND implantation of GammaTiles.
• Willing and able to provide informed consent and to participate in all evaluations.
Exclusion Criteria:
• Inability to undergo pre-operative and post-operative imaging for disease and implant assessment.
• Major medical or psychiatric illness, which, in the investigator's opinion would prevent completion of treatment, ability to complete assessments at the time of enrollment, and/or interfere with follow ups.
• Lack of English language fluency sufficient to allow for completion of neurocognitive and QOL tests (which are in English).
DEVICE: GammaTile
Brain Tumor, Brain Tumor, Recurrent, Brain Tumor, Primary, Brain Tumor - Metastatic, Brain Tumor, Adult: Glioblastoma, Brain Tumor, Adult Meningioma
UT Southwestern
Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging
This phase III trial tests two questions by two separate comparisons of therapies. The first question is whether enhanced therapy (apalutamide in combination with abiraterone + prednisone) added to standard of care (prostate radiation therapy and short term androgen deprivation) is more effective compared to standard of care alone in patients with prostate cancer who experience biochemical recurrence (a rise in the blood level of prostate specific antigen [PSA] after surgical removal of the prostate cancer). A second question tests treatment in patients with biochemical recurrence who show prostate cancer spreading outside the pelvis (metastasis) by positron emission tomography (PET) imaging. In these patients, the benefit of adding metastasis-directed radiation to enhanced therapy (apalutamide in combination with abiraterone + prednisone) is tested. Diagnostic procedures, such as PET, may help doctors look for cancer that has spread to the pelvis. Androgens are hormones that may cause the growth of prostate cancer cells. Apalutamide may help fight prostate cancer by blocking the use of androgens by the tumor cells. Metastasis-directed targeted radiation therapy uses high energy rays to kill tumor cells and shrink tumors that have spread. This trial may help doctors determine if using PET results to deliver more tailored treatment (i.e., adding apalutamide, with or without targeted radiation therapy, to standard of care treatment) works better than standard of care treatment alone in patients with biochemical recurrence of prostate cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kevin Courtney
131906
MALE
18 Years and over
PHASE3
NCT04423211
STU-2022-1154
Inclusion Criteria:
* STEP 0: REGISTRATION ELIGIBILITY CRITERIA
* Patient must be male and \>= 18 years of age.
* Patient must have had a radical prostatectomy (RP) as definitive therapy for histopathologically-proven prostatic adenocarcinoma
* Patient must have biochemical recurrence (BCR) after RP, defined as follows:
* If time to BCR, defined as time to first detectable PSA ( \> lower limit of normal for assay used) after RP, is \< 12 months, a minimum PSA level of \>= 0.2 ng/mL and a confirmatory reading of \>= 0.2 ng/mL is required, per the American Urological Association (AUA) definition (Note: patients with a persistent PSA reading of at least 0.2 ng/mL are eligible)
* If time to BCR, defined as time to first detectable PSA (\> lower limit of normal for assay used) after RP, is \>= 12 months, a minimum absolute PSA of 0.5 ng/mL is required
* If the patient has a detectable PSA (\> lower limit of normal for assay used) at any time after RP AND has an eligible baseline SOC PET (PET1) with at least one positive lesion in any location, then there is no minimum PSA requirement
* Patients must have no definite evidence for extrapelvic metastatic disease by conventional imaging modalities (CIM) (CT abdomen/pelvis or MRI abdomen/pelvis AND bone scintigraphy, or equivalent), within 26 weeks prior to Step 0 registration. If a patient only has a study-eligible PET/CT or PET/MR (i.e., PET done without prior CIM): if the PET is negative for extrapelvic lesions, then baseline CIM is NOT required. If the PET positive for extrapelvic lesions, then patient should have a baseline CT/MRI for soft tissue lesions and/or a bone scan for osseous lesions
* Study eligible = PET using FDA-approved radiotracer and performed within 16 weeks prior to study registration
* Extra-pelvic metastases is defined as any osseous metastases and/or any extrapelvic soft tissue, lymph nodes and organ metastases; extra-pelvic is defined as superior to common iliac bifurcation, outside of standard prostate bed + whole pelvis nodal RT fields. Baseline PET/CT or PET/MR scan (PET1) is eligible for this study if the SOC PET scan is completed with an FDA approved radiotracer for prostate cancer after Step 0 registration and prior to Step 1 randomization OR up to 16 weeks prior to Step 0 registration
* Patient must be a candidate for SOC post-prostatectomy radiation therapy (RT) to the prostate bed and pelvic nodes with androgen deprivation therapy (ADT)
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Patient must not have started ADT for biochemical recurrence prior to baseline PET (PET1) imaging. A short course of low-dose anti-androgen such as bicalutamide, given after baseline study PET/CT but prior to study registration, is permitted as a brief temporizing measure in advance of starting protocol-approved SOC ADT.
* Patient must not be enrolled in another therapeutic clinical trial
* Patient must be able to lie flat and still for approximately 20-30 minutes or otherwise tolerate a PET scan and radiation treatment planning and delivery
* Patients undergoing a PET/MR must meet local institutional safety guidelines for MRI
* Patient must not have history of seizures or known condition that may cause predisposal to seizures (e.g., stroke or head trauma resulting in loss of consciousness) within 1 year prior to registration
* Patient must not have history of inflammatory bowel disease or any gastrointestinal disorder affecting absorption that is expected to increase risk of complication from radiotherapy
* Hemoglobin (Hgb) \>= 9.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to Step 0 registration) (obtained within 8 weeks prior to Step 0 registration)
* Leukocytes \>= 3,000/mcL (obtained within 8 weeks prior to Step 0 registration)
* Absolute neutrophil count \>= 1,500/mcL (obtained within 8 weeks prior to Step 0 registration)
* Platelets \>= 100,000/mcL (obtained within 8 weeks prior to Step 0 registration)
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (patients with Gilbert's syndrome, if total bilirubin is \> 1.5 x ULN, must have a direct bilirubin of \< 1.5 x ULN to be eligible) (obtained within 8 weeks prior to Step 0 registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained within 8 weeks prior to Step 0 registration)
* Creatine \< 1.5 x instituional ULN (or measured creatinine clearance \> 30 mL/min)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class I or II (by patient symptoms) or A or B (by objective assessment)
* Patient must not have completed a course of prior pelvic radiation therapy for any reason
* Patient must agree not to father children while on study
* Patient must be English or Spanish speaking to be eligible for the QOL component of the study
* NOTE: Sites cannot translate the associated QOL forms
* STEP 1: RANDOMIZATION ELIGIBILITY CRITERIA
* Patient must have completed a baseline SOC PET/CT or PET/MR (PET1 scan) using FDA approved radiotracer with results of extra-pelvic metastases involvement known (positive or negative). The PET1 must have been completed after Step 0 registration and prior to Step 1 randomization OR up to 12 weeks prior to Step 0 registration
* For patients with negative extra-pelvic metastases, PET-imaging status of intra-pelvic nodes must be known (positive or negative)
* For patients with positive extra-pelvic metastases (defined as any PET positive lesions outside of standard salvage RT fields \[prostate bed +/- typical whole pelvis\]), the number of extra-pelvic lesions must be known (1 - 5 or \> 5 extra-pelvic lesions) RADIATION: 3-Dimensional Conformal Radiation Therapy, DRUG: Apalutamide, PROCEDURE: Computed Tomography, DRUG: Degarelix, RADIATION: External Beam Radiation Therapy, OTHER: Fluciclovine F18, DRUG: Goserelin Acetate, PROCEDURE: Intensity-Modulated Proton Therapy, RADIATION: Intensity-Modulated Radiation Therapy, DRUG: Leuprolide Acetate, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, DRUG: Relugolix, RADIATION: Stereotactic Body Radiation Therapy, DRUG: Triptorelin, RADIATION: Volume Modulated Arc Therapy
Prostate Adenocarcinoma, Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8, Biochemically Recurrent Prostate Carcinoma
UT Southwestern; Parkland Health & Hospital System
A Phase 1/2, Open-label, Safety and Dosing Study of Autologous CART Cells (Desmoglein 3 Chimeric Autoantibody Receptor T Cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T Cells [CABA-201]) in Subjects With Active, Pemphigus Vulgaris (RESET-PV)
A phase 1/2, open-label, safety and dosing study of autologous CART cells (desmoglein 3 chimeric autoantibody receptor T cells [DSG3-CAART] or CD19-specific Chimeric Antigen Receptor T cells [CABA-201]) in subjects with active, pemphigus vulgaris
Aleuna Lee aleuna.lee@utsouthwestern.edu
ALL
18 Years and over
PHASE1
NCT04422912
Inclusion Criteria:
* Confirmed diagnosis of mPV by prior or screening biopsy and prior positive anti- DSG3 antibody ELISA
* mPV inadequately managed by at least one standard immunosuppressive therapies
* Active mPV at screening
* Anti-DSG3 antibody ELISA positive at screening
Inclusion Criteria for CABA-201 sub-study
* Confirmed diagnosis of PV by prior or screening biopsy and prior positive DSG3 ELISA, IIF, and/or DIF
* PV inadequately managed by at least one standard immunosuppressive therapy
* Active PV at screening
* DSG3 ELISA positive at screening
Exclusion Criteria:
* Active cutaneous lesions associated with PV that indicates mucocutaneous rather than mucosal-dominant disease
* Rituximab in last 12 months unless PV symptoms have recently worsened or anti-DSG3 antibody titers have recently increased
* Prednisone \> 0.25mg/kg/day
* Other autoimmune disorder requiring immunosuppressive therapies
* Investigational treatment in last 3 months
Exclusion Criteria for CABA-201 sub-study
* Have paraneoplastic pemphigus or active malignancy (not including non-melanoma skin cancer)
* Have received rituximab or other anti-CD20 or anti-CD19 therapies in last 12 months unless anti-DSG3 antibody titers have recently increased or PV symptoms have recently worsened
* Prednisone \> 0.25mg/kg/day
* Other autoimmune disorder requiring immunosuppressive therapies
* Investigational treatment in last 3 months BIOLOGICAL: DSG3-CAART or CABA-201
Pemphigus Vulgaris
Pemphigus, Pemphigus Vulgaris, CAAR-T Therapy, CAR-T Therapy, Desmoglein 3, Cell Therapy, Autoimmune Disease, Autoimmunity, Skin Diseases, Vesiculobullous, Immunotherapy, Adoptive, Immune System Diseases, CABA-201, Anti-CD19 CAR-T therapy
Study to Evaluate the Safety and Tolerability of CC-94676 in Participants With Metastatic Castration-Resistant Prostate Cancer
The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CC-94676 in men with progressive metastatic castration resistant prostate cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kevin Courtney
131906
MALE
18 Years and over
PHASE1
NCT04428788
STU-2022-0475
Inclusion Criteria:
* Must have histologically or cytologically confirmed adenocarcinoma of the prostate
* Progressed on androgen deprivation therapy (ADT) and at least one prior secondary hormonal therapy approved for castration-resistant prostate cancer (CRPC)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Exclusion Criteria:
* Prior treatment with an androgen receptor (AR) degrader
* Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 1 year prior to the first dose of IP
* Clinically significant venous thromboembolism within 3 months prior to the first dose of IP
* Any significant medical condition, such as uncontrolled infection, laboratory abnormality, or psychiatric illness
Other protocol-defined inclusion/exclusion criteria apply DRUG: CC-94676, DRUG: CC1083611, DRUG: CC1083610
Prostatic Neoplasms
Prostate Cancer, CC-94676, Castration-resistant prostate cancer, Adenocarcinoma of the prostate, Prostatic Neoplasms Castration-Resistant, Neoplasms
UT Southwestern
HYPORT: A Phase I/II Study of Hypofractionated Post-operative Radiation Therapy for Head and Neck Cancer
There is a strong radiobiological and economic rationale for hypofractionated radiation therapy in head and neck cancer. Phase 1 of the trial aims to assess the acute toxicity and tolerability of hypofractionated radiation therapy in the post-operative setting, and to determine the dose/fractionation for Phase 2. Phase 2 aims to establish non-inferiority of swallowing-related quality of life and to assess the toxicity and efficacy of hypofractionated radiation therapy compared to conventionally fractionated radiation therapy in the post-operative setting.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Dominic Moon
189455
All
18 Years and over
Phase 1/Phase 2
NCT04403620
STU-2020-0522
Inclusion Criteria:
Inclusion criteria will be the same for Phase I and Phase II.
• Pathologically proven diagnosis of stage I-IVB squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx status post gross total resection with pathology showing one or more of the following intermediate risk factors:
• T3/4 disease (AJCC 8th edition), positive lymph node(s), close margin(s), perineural invasion, and/or lymphovascular invasion
• Close margin(s) defined as either:
• Final patient margin of <5 mm without disease on ink OR
• Initial positive margin in the specimen regardless of the final patient margin (e.g. if resection margin on the initial specimen is positive, final patient margin after subsequent resections can be ≥5 mm and still be considered close margin)
• Age ≥18 years
• ECOG performance status 0-2
• 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. Medically acceptable birth control (contraceptives) includes:
• approved hormonal contraceptives (such as birth control pills, patch or ring; Depo-Provera, Implanon), or
• barrier methods (such as condom or diaphragm) used with a spermicide 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, 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).
• Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential.
• Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
Phase I:
• Distant metastasis
• Stage I and II glottic squamous cell carcinoma
• High risk factors following surgical resection requiring concurrent chemotherapy: final positive margin(s) and/or extranodal extension
• Feeding tube dependence at baseline assessment.
• Synchronous non-skin cancer primaries outside of the oropharynx, oral cavity, larynx, and hypopharynx except for low- and intermediate-risk prostate cancer and synchronous well-differentiated thyroid cancer. For prostate cancer, patient should not be receiving active treatment. For thyroid cancer, thyroid surgery may occur before or after treatment, provided all other eligibility criteria are met.
• Prior invasive malignancy with an expected disease-free interval of less than 3 years
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields
• Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 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.
• History of severe immunosuppression, including HIV, and organ or autologous or allogeneic stem cell transplant Phase II: The exclusion criteria will be the same as Phase I except for feeding tube dependence. Patients who are feeding tube dependent are excluded from Phase I to accurately assess treatment associated toxicity affecting swallowing and oral intake. During Phase II, patients who are feeding tube dependent will be eligible to enroll and stratified at randomization.
Radiation: Intensity-modulated Radiation Therapy (IMRT)
Head and Neck, Squamous Cell Carcinoma of Head and Neck
Radiation Dose Hypofractionation, Adjuvant Radiotherapy
UT Southwestern; Parkland Health & Hospital System
Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous NSCLC
To determine the efficacy of combined afatinib and prednisone in previously treated advanced squamous NSCLC
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Sheena Bhalla
203321
ALL
18 Years and over
PHASE2
NCT04497584
STU-2020-1363
Inclusion Criteria:
* Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
* Previously treated (up to three prior lines of therapy), histologically proven advanced squamous NSCLC.
* No prior treatment with EGFR inhibitors, IMIDs (eg, thalidomide, lenalidomide), or anti-TNF antibodies.
* No treatment with systemic glucocorticoids within 3 weeks of initiation of study therapy (topical and inhaled glucocorticoids are permitted).
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ and marrow function as defined below:
* absolute neutrophil count ≥ 1,000/μL
* platelets ≥ 50,000/μl
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
* CrCl ≥ 45 ml/min
* For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
* Adequate archival tissue (5-10 slides) for correlative studies.
* Subject must have measurable disease per RECIST 1.1
Exclusion Criteria:
* Chemotherapy, radiotherapy, or other cancer therapy within two weeks prior to starting study treatment. Subjects must have recovered from prior treatment-related to toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment).
* Subjects may not be receiving any other investigational agents for the treatment of the cancer under study.
* Symptomatic brain metastases or brain metastases requiring escalating doses of corticosteroids
* History of hypersensitivity or allergic reactions attributed to afatinib or prednisone.
* Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes (which may worsen in setting of chronic prednisone therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or 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. DRUG: Afatinib + Prednisone
Advanced Squamous Non Small Cell Lung Cancer
UT Southwestern; Parkland Health & Hospital System
Evolutionary Therapy for Rhabdomyosarcoma
This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Matthew Campbell
108757
ALL
Not specified
PHASE2
NCT04388839
STU-2020-0815
Inclusion Criteria:
* Participants must have a new histologic diagnosis of rhabdomyosarcoma
* Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
* Participants must have sufficient tissue (up to 10 unstained FFPE) for correlative testing
* All participants must have distant metastatic disease; either biopsy positive or PET avid extranodal or distant nodal lesions determined by the investigator to be metastatic disease. Patients with a single distant metastatic site that has been excised prior to study entry are eligible
* No prior systemic chemotherapy
* Participants enrolled to Arm B, maintenance, must be able to take oral cyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.
* Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence.
* Women of childbearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
* Men who are sexually active with women of child bearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
* All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.
Exclusion Criteria:
* Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible
* Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible
* Participants must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis based products would not be a reason for exclusion
* Participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to:
* ongoing or active infection not expected to resolve with current antibiotic plan
* cardiac arrhythmia
* psychiatric illness/social situations that would limit compliance with study requirements
* Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy.
* Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible DRUG: Vincristine, DRUG: Cyclophosphamide, DRUG: Vinorelbine, DRUG: Actinomycin D, DRUG: Cyclophosphamide Pill
Rhabdomyosarcoma
Soft Tissue Cancer, Skeletal Muscle Tissue Cancer, Sarcoma
Children’s Health
The ExTINGUISH Trial of Inebilizumab in NMDAR Encephalitis (ExTINGUISH)
Determine the difference in the modified Rankin score at 16 weeks in participants with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis treated with "first-line" immunomodulatory therapies provided as standard-of-care, and either inebilizumab (investigational agent) or placebo.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Taylor.Hinojo@UTSouthwestern.edu
Kyle Blackburn
156805
All
18 Years and over
Phase 2
NCT04372615
STU-2021-1105
Inclusion Criteria:
• Inclusion Criteria 1. Diagnosis of NMDAR encephalitis, defined by both (a) and (b):
• A subacute onset of change in mental status consistent with autoimmune encephalitis,
• A positive cell-based assay for anti-NMDA receptor IgG antibody in the CSF confirmed in study-specified laboratories.
• Age ≥ 18 years 3. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPAA] in the United States of America (USA), European Union [EU] Data Privacy Directive in the EU) obtained from the participant/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must agree to use a highly effective method of contraception beginning at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 6 months after the final dose of investigational product.
• Nonsterilized males who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception at screening or upon discharge from hospitalization/inpatient rehabilitation (for participants who were incapacitated at the time of screening), and to continue precautions for 3 months after the final dose of investigational product. Male patients with female partners of childbearing potential must have that female partner use at least one form of highly effective contraception, starting at least one menstrual cycle before (the male patient's) first study drug administration and continuing until at least 3 months after their male partner's last dose of the study drug.
• Willing to forego other immunomodulatory therapies (investigational or otherwise) for NMDAR encephalitis during the study.
• Patient must have received at least 3 days of methylprednisolone 1000 mg IV or equivalent corticosteroid within 30 days prior to randomization (Day 1). In addition, patients must have received EITHER of the following treatments within 30 days before randomization.
• IVIg, at a minimum dose of 2 g/kg
• Plasma exchange or plasmapheresis, with a minimum of 5 treatments. NOTE: These treatments may be provided during the screening period, but must be completed prior to randomization.
• mRS of ≥3 at the screening visit, indicating at least moderate disability. 9. Ability and willingness to attend study visits and complete the study
Exclusion Criteria:
• Any condition that, in the opinion of the investigator, would interfere with the evaluation or administration of the investigational product, interpretation of participant safety or study results, or would make participation in the study an unacceptable risk. This specifically includes recent history (last 5 years) of herpes simplex virus encephalitis or known central nervous system demyelinating disease (e.g., multiple sclerosis).
• Presence of an active or chronic infection that is serious in the opinion of the investigator.
• Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 published half-lives of the investigational treatment, whichever is the longer, prior to randomization.
• Lactating or pregnant females, or females who intend to become pregnant anytime from study enrollment to 6 months following last dose of investigational agent.
• Known history of allergy or reaction to any component of the investigational agent formulation or history of anaphylaxis following any biologic therapy.
• At screening (one repeat test may be conducted to confirm results prior to randomization within the same screening period), any of the following:
• Aspartate transaminase (AST) > 2.5 × upper limit of normal (ULN)
• Alanine transaminase (ALT) > 2.5 × upper limit of normal (ULN)
• Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome)
• Platelet count < 75,000/μL (or < 75 × 109/L)
• Hemoglobin < 8 g/dL (or < 80 g/L)
• Total white blood count <2,500 cells/mm3
• Total immunoglobulin < 600 mg/dL
• Absolute neutrophil count < 1200 cells/μL
• CD4 T lymphocyte count < 300 cells/µL
• Receipt of the following at any time prior to randomization:
• Alemtuzumab
• Total lymphoid irradiation
• Bone marrow transplant
• T-cell vaccination therapy
• Receipt of rituximab or any experimental B-cell depleting agent, unless the CD19 B-cell level has returned to above the lower limit of normal prior to randomization.
• Receipt of any of the following within 3 months prior to randomization
• Natalizumab (Tysabri®)
• Cyclosporine
• Methotrexate
• Mitoxantrone
• Cyclophosphamide
• Azathioprine
• Mycophenolate mofetil
• Severe drug allergic history or anaphylaxis to two or more food products or medicines (including known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, and methylprednisolone or equivalent glucocorticoid).
• Known history of a primary immunodeficiency (congenital or acquired) or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infection.
• Confirmed positive test for hepatitis B serology (hepatitis B surface antigen and core antigen) and/or hepatitis C PCR positive at screening.
• History of cancer, apart from ovarian or extra-ovarian teratoma (also known as a dermoid cyst) or germ cell tumor, or squamous cell carcinoma of the skin or basal cell carcinoma of the skin. Squamous cell and basal cell carcinomas should be treated with documented success of curative therapy > 3 months prior to randomization.
• Any live or attenuated vaccine within 3 weeks prior to Day 1 (administration of killed vaccines is acceptable).
• Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of enrollment.
• Recurrence of previously treated NMDAR encephalitis within the last 3 or 5 years, or suspicion of symptomatic untreated NMDAR encephalitis of greater than 3 months duration at the time of screening.
Drug: Inebilizumab, Drug: Placebo
Autoimmune Encephalitis, Brain and Nervous System, Encephalitis
Inebilizumab, NMDAR encephalitis, Autoimmune Encephalitis, Rare Disease
UT Southwestern
Study of CHS-388 (Formerly Known as SRF388) in Patients With Advanced Solid Tumors
This is a Phase 1/1b, open-label, first-in-human, dose-escalation and expansion study of CHS-388, a monoclonal antibody that targets IL-27, as a monotherapy and in combination in patients with solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
169573
ALL
18 Years and over
PHASE1
NCT04374877
STU-2020-0969
Part A and Part B Abbreviated
Inclusion Criteria:
* ≥ 18 years of age
* Locally advanced or metastatic (Stage IV) solid tumor that has progressed during or after standard therapy, and for whom no available therapies are appropriate (based on investigator judgment)
* Patients in Part B with advanced or metastatic ccRCC, HCC, or NSCLC must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Patients with HCC in Part B must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC1) Stage B (not eligible for transcatheter arterial chemoembolization \[TACE\]) or Stage C
* For patients in Part B with ccRCC, demonstrated progressive disease (PD) during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with regimen(s) that have included a vascular endothelial growth factor (VEGF)-targeted agent and an immune checkpoint inhibitor. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For patients in Part B with HCC, demonstrated PD during or after the most recent treatment regimen. Prior treatment history must include progression during or after treatment with a VEGF-targeted agent. Patients who did not progress on but discontinued the VEGF-targeted agent for toxicity or intolerability are permitted.
* For Part B patients in the tumor biopsy subsets only, must have tumor tissue that is accessible for pretreatment and on-treatment tumor biopsy in the opinion of the Investigator and be willing to undergo pretreatment and on-treatment biopsies per protocol
* Serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula or serum creatinine ≤ 2.0 x the upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if elevated because of Gilbert's syndrome and ≤ 2 x ULN for patients with HCC or patients with known liver metastases)
* Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) \< 2.5 x ULN (\< 5 x ULN if liver metastasis or for patients with HCC)
* For patients with HCC, Child-Pugh class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Adequate hematologic function, defined as absolute neutrophil count (ANC) ≥ 1.0 x 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 x 109/L. For patients with HCC, platelet count ≥ 75 x 109/L without transfusion
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patients with NSCLC must have histologically confirmed locally advanced and/or metastatic Stage IV NSCLC
* Patients with NSCLC must have demonstrated progressive disease during or after the most recent treatment regimen
Part C Abbreviated Inclusion Criteria:
* ≥ 18 years of age
* Advanced RCC of any histology or advanced HCC previously treated with at least one systemic anticancer therapy OR histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* Patients with HCC must have unresectable disease, Barcelona Clinic Liver Cancer (BCLC) Stage B (not eligible for transcatheter arterial chemoembolization) or Stage C
* At least 1 measurable lesion per RECIST 1.1
* Patients with HCC must have at least 1 measurable target lesion according to modified RECIST (mRECIST)
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL; for participants with HCC: ≥8.5 g/dL
* 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
* For patients with HCC, Child-Pugh Class A or B7 with a serum albumin ≥ 2.8 g/dL (≥ 28 g/L)
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 120 days after the last dose of pembrolizumab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part C Abbreviated Inclusion Criteria Specific to Patients with RCC or HCC from Part A or Part B:
* Progressed on CHS-388 by RECIST 1.1
* Did not experience prior Grade ≥ 3 toxicity related to CHS-388
* Willingness to undergo pretreatment core or excisional biopsy if deemed safe and tumor is accessible, in the opinion of the Investigator
* Has received no systemic anticancer therapies between CHS-388 doses
Part C Abbreviated Inclusion Criteria specific to NSCLC Patients:
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
Part A and Part B Abbreviated Exclusion Criteria:
* Previously received an anti-IL-27 antibody or anti-IL-27 targeted therapy
* For patients in Part B with renal cell carcinoma (RCC), non-clear cell RCC histology
* For patients with HCC, known fibrolamellar or mixed hepatocellular cholangiocarcinoma
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Major surgery within 4 weeks prior to Screening
* Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition including pneumonitis and/or interstitial lung disease, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part C Abbreviated Exclusion Criteria:
* 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 drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* For patients with HCC, fibrolamellar histology or mixed hepatocellular cholangiocarcinoma
* For patients with HCC, moderate or severe ascites
* For patients with HCC, inability to undergo disease evaluation with triphasic computed tomography or magnetic resonance imaging because of contrast allergy or other contraindication
* For patients with HCC, imaging findings consistent with ≥ 50% liver occupation by HCC tumors
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study
Part D Abbreviated Inclusion Criteria
* ≥ 18 years of age
* Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma or squamous cell NSCLC
* No more than 3 prior lines of systemic therapy for unresectable or metastatic disease with prior radiologic progression on or following platinum-based chemotherapy and prior anti-PD-(L)1 therapy whether given alone or in combination
* At least 1 measurable lesion per RECIST 1.1
* ECOG performance status of 0-1
* ANC ≥1500/µL (1.5 x 109/L)
* Platelets ≥100 000/µL (≥ 100 x 109/L)
* Hemoglobin for participants with RCC: ≥9.0 g/dL
* 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
* Willingness of male and female patients who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study drug period (or beginning 14 days before the initiation of pembrolizumab for oral contraception), including 75 days after the last dose of CHS-388 or 180 days after the last dose of toripalimab; male patients must refrain from donating sperm during this period. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception with spermicide. Azoospermic male patients and WCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, female patients must still undergo pregnancy testing as described in this section.
Part D Abbreviated Exclusion Criteria:
* 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 drug
* Previously received an anti-IL 27 antibody or anti-IL 27 targeted therapy (exception to patients who received CHS-388 in Part A or Part B)
* No prior systemic therapy for unresectable or metastatic disease
* Received \> 4 prior systemic regimens for unresectable or metastatic disease (prior PD-(L)1 inhibitors are allowed if the patient did not discontinue therapy due to ≥ Grade 3 drug-related toxicity)
* 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 (e.g., CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a ≥ Grade 3 irAE.
because of contrast allergy or other contraindication
* History of Grade 4 allergic or anaphylactic reaction to any monoclonal antibody therapy or any excipient in the study drugs
* Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration
* Prior autologous stem cell transplant ≤ 3 months before the first dose
* Prior allogeneic hematopoietic cell transplant within 6 months of the first dose or with a history of or current clinical Graft-Versus-Host Disease
* Has had an allogenic tissue/solid organ transplant
* Other unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the risk to the patient associated with his or her participation in the study DRUG: CHS-388, DRUG: Pembrolizumab, DRUG: Toripalimab
Non-Small Cell Lung Cancer, Hepatocellular Carcinoma, Clear Cell Renal Cell Carcinoma, Advanced Solid Tumor
metastatic solid tumors, advanced solid tumors, Phase 1, CHS-388, IL-27, safety, efficacy, immunotherapy, cancer, immuno-oncology, kidney cancer, renal cell carcinoma, liver cancer, hepatocellular carcinoma, non-small cell lung cancer, pembrolizumab, PD-1, toripalimab, SRF388
UT Southwestern