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Diuretic Tuner Clinical Decision Support
This purpose of this study is to determine the effectiveness of a mobile phone application in helping to control body swelling in patients with kidney problems. The application will help in the day to day adjustments in diuretic medication dosing. Participants in this study will have an application loaded on to their mobile phone by the study team and be taught how to use it over a 2 hour visit. Participants will need to check their blood pressure and weight daily and enter this information into the mobile phone application every day. Participants will need to follow daily instructions in their medication dosing provided by the application. There will be periodic blood testing. This will happen at 2 weeks, 90 days, and up to 4 other times if necessary. At the end of the study there is a 2 hour study visit during which participants will answer a survey. The total length of the study is 90 days.
Call 214-648-5005
studyfinder@utsouthwestern.edu, KSAMBANDAM@UTSouthwestern.edu
Kamalanathan Sambandam
All
18 Years and over
N/A
NCT04759274
STU-2020-1124
Inclusion Criteria:
• The presence of nephrotic range proteinuria (> 3 g/d proteinuria by 24hr urine protein, 24hr urine albumin, spot urine protein/creatinine ratio, or spot urine albumin/creatinine ratio) or stage 4 or 5 chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease equation) PLUS
• Clinical signs of hypervolemia present (lower extremity edema, ascites, or pleural effusions) with an estimated dry weight (defined as edema-free weight without orthostatic hypotension) 5 lbs less than enrollment body weight
Exclusion Criteria:
• Weight < 100 lbs or > 300 lbs.
• Autonomic insufficiency resulting in orthostatic hypotension at screening
• Hypokalemia at enrollment (defined as serum potassium < 3.5 mmol/L)
• Moderate to severe hyponatremia at enrollment (defined as serum sodium < 130 mmol/L)
• Serum creatinine > 6 mg/dL or > 1.5 times baseline
• Patients who are unable or unwilling to measure their home blood pressures and weights
• Patients without a working phone number and smart phone device
• Expectation that the patient will require dialysis initiation within < 3 months
• Expected lifespan of < 6 months
• The presence of a medical condition that would interfere with effectively using the Diuretic Tuner (dementia, illiteracy, or blindness)
• Pregnant patients
• Prisoners
Device: Diuretic Tuner
Edema, Hypervolemia, Chronic Kidney Diseases, Nephrotic Syndrome, Kidney
UT Southwestern; Parkland Health & Hospital System
Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)
We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-18 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 20 core clinical sites.
Call 214-648-5005
studyfinder@utsouthwestern.edu, melaku.lemma@childrens.com
Raymond Quigley
ALL
6 Years to 18 Years old
PHASE2
NCT04741646
STU-2020-1055
Inclusion Criteria:
• Ages 6 to 18 years (inclusive);
• Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) under 25 (U25) formula;56
• Serum phosphate \<=5.9 mg/dl;
• Serum ferritin \<500 ng/ml and TSAT \<50%;
• For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (ESAs) such treatments must have stable dosing for at least 2 weeks prior to screening;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Exclusion Criteria:
• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease.
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Cystinosis
• Fanconi syndrome
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
DRUG: Ferric Citrate, DRUG: Placebo
Chronic Kidney Diseases, Kidney
Pediatric, CKD, Phosphate Binder
Children’s Health
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, 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 methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine 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. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT04628767
STU-2021-0698
Inclusion Criteria:
* STEP 1 REGISTRATION AND RANDOMIZATION
* Patients must be \>= 18 years of age
* 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 a diagnosis of high grade upper tract urothelial carcinoma expected within 14 weeks (98 days) prior to registration/randomization with one of the following:
* Biopsy (gold standard, preferred) and either upper urinary tract mass on cross-sectional imaging or tumor directly visualized during upper urinary tract endoscopy
* High grade cytology and clinically estimated invasive upper urinary tract mass on cross-sectional imaging (e.g., including presence of tumor-related hydronephrosis) or tumor directly visualized during upper urinary tract endoscopy
* NOTE: Universal histologic testing of UTUC with additional studies, such as immunohistochemistry and/or microsatellite instability, is strongly recommended to identify patients with high probability of Lynch-related or other germline mutation related cancers whom clinicians should refer for genetic counseling and germline testing (this is not required for eligibility)
* Due to the anatomy of upper urinary tract and lack of muscularis propria, pathologic evidence of cT2 on biopsy is usually not possible
* Patients must not have any component of small cell/neuroendocrine carcinoma. Other histologic subtypes (variants) are permitted provided the half or predominant (\>= 50%) subtype is conventional urothelial carcinoma
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Total bilirubin =\< 1.2 mg/dL (or ≤ 2 mg/dL for patients with Gilbert's disease)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x institutional ULN (obtained =\< 14 days prior to registration/randomization)
* Hemoglobin (Hgb) \>= 9 g/dL (obtained =\< 14 days prior to registration/randomization)
* NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
* Patients 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 patient, regardless of 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 of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
* Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (\>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings \>=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) scan or other imaging or other criteria can be eligible based on investigator discretion).
* NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scan to evaluate for bone metastasis at the discretion of local provider.
* Patient must meet below criteria for prior/current malignancy history:
* Non-urothelial cancer malignancy history:
* Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =\< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
* NOTE: Patients with 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.
* Urothelial cancer malignancy history:
* Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
* T0, Ta or Tis at any time
* T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy \[e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)\]. Prior systemic immune checkpoint inhibitor is not allowed.
* Patient with history of \>= pT4b, N+, and/or M1 UC is not eligible.
* NOTE: Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (\< cT1 N0) are eligible regardless of time elapsed
* Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations in the three months prior to registration that would limit compliance with study requirements
* Patient must not have received prior radiation therapy to \>= 25% of the bone marrow for other diseases
* Patient must not have received prior systemic anthracycline therapy
* NOTE: Patients who have received prior intravesical therapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
* Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease \[IBD\], e.g. ulcerative colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
* Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion and are allowed:
* Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
* Steroids as pre-medications for hypersensitivity reactions (e.g. computed tomography \[CT\] pre-medication)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial
* NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
* NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of registration/randomization
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab
* Patient must not have had a major surgical procedure within 28 days prior to registration/randomization
* NOTE: Cystoscopy/ureteroscopy/TURBT, stent placement or nephrostomy tube is not considered major surgery
* Patient must not have history of allogenic organ transplantation
* Patient must have a body weight of \> 30 kg
* Patient must have life expectancy of \>= 12 weeks
* Patient must have creatinine clearance \> 15 ml/min as estimated by Cockcroft-Gault formula or glomerular filtration rate (GFR) \> 15 ml/min/1.73m\^2 within 28 days prior to registration/randomization
* NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with recommended cisplatin contraindications. Patients who are cisplatin-eligible will be randomized to either Arm A or Arm B and patients who are cisplatin-ineligible will be registered to Arm C
* Patients that meet any of the following four criteria will be registered to the cisplatin-ineligible Arm C if they meet other eligibility criteria:
* Creatinine clearance \> 15 ml/min and =\< 50 ml/min (estimated by Cockcroft-Gault formula) or GFR \> 15ml/min/1.73m\^2 and ≤ 50 ml/min/1.73 m\^2
* Hearing loss \>= 3
* Neuropathy \>= 2
* ECOG performance status 2
* In addition, the patient must have an absolute neutrophil count (ANC) \>= 1,000/mcL obtained =\< 14 days prior to registration
* Patients that meet all of the following four criteria will be randomized to the cisplatin-eligible Arm A or Arm B:
* Creatinine clearance \> 50ml/min (estimated by Cockcroft-Gault formula) or GFR \> 50ml/min/1.73m\^2
* ECOG performance status 0-1
* Hearing loss grade 0-2
* Neuropathy 0-1
* In addition, the patient must have an absolute neutrophil count (ANC) \>= 1,500/mcL obtained =\< 14 days prior to randomization
* Also, the patient must have left ventricular ejection fraction (LVEF) \>= 50% by (either multigated acquisition scan \[MUGA\] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Durvalumab, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Vinblastine Sulfate
Renal Pelvis and Ureter Urothelial Carcinoma, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
Post-market Surveillance Study of the BD® WavelinQ™ EndoAVF System (CONNECT-AV)
A prospective, single-arm, multi-center post-market surveillance study of the BD® WavelinQ™ EndoAVF System for the Creation of Arteriovenous (AV) Fistula in Patients Requiring Dialysis.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Camille.Harry@UTSouthwestern.edu
Aria Nazeri
ALL
18 Years to old
NA
NCT04634916
STU-2024-0152
Inclusion Criteria:
• Subject must be either male or non-pregnant female ≥ 18 years of age with an expected lifespan sufficient to allow for completion of all study procedures.
• Subject must voluntarily sign and date the Informed Consent Form (ICF) prior to collection of study data or performance of study procedures.
• Subject must be willing to comply with the protocol requirements, including clinical follow-up.
• Subjects who have established, non-reversible kidney failure, who are currently on dialysis at screening or are in immediate need (within 6 months of endoAVF creation) of dialysis.
• Target treatment vein diameter(s) for endoAVF creation ≥ 2.0 mm as measured via Duplex Ultrasound (DUS) or Venography.
• Target treatment artery diameter ≥ 2.0 mm as measured via Duplex Ultrasound (DUS) or Arteriogram.
• Subject has adequate collateral circulation to the hand, in the opinion of the Investigator.
• At least one superficial outflow vein diameter ≥ 2.5 mm and in communication with the target creation site via a proximal forearm perforating vein.
Exclusion Criteria:
• The subject is in a hypercoagulable state.
• The subject has known bleeding diathesis.
• The subject has insufficient cardiac output to support a native fistula in the opinion of the Investigator.
• Known history of active intravenous drug abuse.
• "Planned" major surgical procedure within 6 months following index procedure or major surgery within 30 days prior to index procedure.
• The subject has a known allergy or hypersensitivity to contrast media which cannot be adequately pre-medicated.
• The subject has known adverse effects to sedation and/or anesthesia which cannot be adequately pre-medicated.
• Evidence of active infection on the day of the index procedure (temperature of ≥ 38.0° Celsius and/ or WBC of ≥ 12,000 cells/ μL, if collected).
• The subject has another medical condition, which, in the opinion of the Investigator, may cause him/her to be non-compliant with the protocol, confound the data interpretation, or is associated with a life expectancy insufficient to allow for the completion of study procedures and follow-up.
• The subject is currently participating in an investigational drug or another device study that has not completed the study treatment or that clinically interferes with the study endpoints. Note: Studies requiring extended follow-up visits for products that were investigational, but have since become commercially available, are not considered investigational studies.
• The subject has central venous stenosis or central vein narrowing \> 50% based on imaging on the same side as the planned endoAVF creation.
• Absence of a proximal forearm perforating vein feeding the target cannulation vein(s) from the target creation site via Duplex Ultrasound (DUS) or Venography.
• Occlusion or stenosis \> 50% of target cannulation vein(s) such as cephalic, median cubital, basilic, etc. assessed via Duplex Ultrasound (DUS) or Venography.
• Significantly compromised venous or arterial flow in the treatment arm as determined by Investigator and Duplex Ultrasound (DUS) or Venography.
• Presence of significant calcification at the target endoAVF location that could potentially impact the effectiveness of endoAVF creation as determined by the Investigator.
DEVICE: EndoAVF Creation
Kidney Disease, End-Stage, End-stage Renal Disease, Arteriovenous Fistula
EndoAVF
Parkland Health & Hospital System
Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor
This phase I/II trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Years to 39 Years old
PHASE2
NCT04616560
STU-2021-0273
Inclusion Criteria:
* Phase 1 (Part A): Patients must be at least 2 years and less than 12 years of age at the time of study enrollment
* Phase 2: Wilms tumor patients (Part B1): All Wilms tumor patients enrolled must be less than 18 years of age at enrollment
* Until the completion of the Phase 1 dose confirmation, patients must be at least 12 years of age and less than 18 years of age at the time of study enrollment
* Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, Wilms tumor patients at least 2 to less than 18 years of age will be allowed on the Phase 2 component
* Phase 2: DSRCT patients (Part B2): Until the completion of the Phase 1 component, patients enrolling on the Phase 2 component of the study must be from at least 12 to 39 years of age at the time of study enrollment
* Following dose confirmation of DS-8201a in children at least 2 to less than 12 years old in the Phase 1 component, DSRCT patients at least 2 to 39 years of age will be allowed on the Phase 2 component
* Patients must have had histologic verification of Wilms tumor or desmoplastic small round cell tumor at original diagnosis or relapse
* Solid tumors: Patients must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Patients with clinically inactive brain metastases may be included in the study. Patients with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. Lastly, patient must have unresectable lesions or lesions with no intention to surgically remove the lesions in the 6 months following enrollment
* Wilms tumor: WT patients must have either refractory disease or a very high risk relapse, defined as ANY of the following:
* Relapse after initial treatment with 4 or more chemotherapy agents (e.g. Regimens vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide and radiation \[M\], vincristine, dactinomycin and doxorubicin, vincristine, and irinotecan \[MVI\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide and radiation \[UH-1\], doxorubicin, vincristine, cyclophosphamide, carboplatin, etoposide, vincristine, and irinotecan \[UH-2\], vincristine, irinotecan, cyclophosphamide, carboplatin, etoposide and doxorubicin \[UH-3\], and etoposide, carboplatin, cyclophosphamide, and doxorubicin \[HR-1\])
* Relapse with high risk histology (anaplasia, blastemal predominant)
* Multiple relapses
* Desmoplastic small round cell tumor: DSRCT patients with relapsed or refractory disease are eligible
* Patient's current disease state must be one for which they have received at least standard initial therapy, defined as systemic therapy combined with either radiation or surgery for local control of the primary tumor at diagnosis. Prior therapy after relapse is not required
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0 or 1. Use Karnofsky for patients older than 16 years of age and Lansky for patients 16 years of age and younger
* Patients must have recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent
* Antibodies: \>= 4 weeks (28 days) must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion the infusion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* Radiation therapy (XRT)/external beam irradiation including protons: \>= 4 weeks (28 days) including palliative radiation therapy to the chest. \>= 14 days after palliative local XRT to areas other than the chest or for whole brain radiotherapy
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, samarium): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior HER2 therapies including antibody drug conjugates (e.g. TDM-1 or DS-8201a), HER2 directed cellular therapies, HER2 receptor therapy (e.g. trastuzumab, pertuzumab, margetuximab, zanidatamab, zenocutuzumab) or small molecule antagonists of HER2 (e.g lapatinib, tucatinib, or neratinib). Prior exposure to antibody drug conjugates which do not target HER2 as well as prior treatment with topoisomerase 1 inhibitors (e.g. irinotecan, topotecan) are permitted
* Patients must be at least 14 days from the date of last surgery
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL, (for patients with solid tumors without known bone marrow involvement)
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (for patients with solid tumors without known bone marrow involvement)
* Hemoglobin \>= 8.0 g/dL at baseline (Red Blood Cell transfusion is not allowed within 1 week prior to enrollment) (for patients with solid tumors without known bone marrow involvement)
* For patients less than or equal to 17 years old, "Bedside" Schwartz formula (2009)
* Estimated glomerular filtration rate (GFR) (eGFR) ≥ 70 mL/min/1.73 m\^2 (\> 70mL/min/1.73 m\^2 for patients \> 17 years old)
* For patients older than 17 years of age the Cockroft-Gault equation should be utilized to calculate creatinine clearance ≥ 70 ml/min:
* OR for any age group:
* A 24 hour urine creatinine clearance ≥ 70 mL/min/1.73 m\^2 (\> 70mL/min for patients ≥ 17 years old) OR
* A directly measured GFR ≥ 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age. For patients with documented Gilbert's syndrome (unconjugated hyperbilirubinemia) bilirubin must be \< 3 x ULN for age (patients with solid tumors)
* Aspartate aminotransferase (AST) =\< 3 x ULN
* Serum albumin \>= 2.5 g/dL (patients with solid tumors)
* International normalized ratio (INR)/prothrombin time (PT) =\< 1.5 x ULN. Exception for patients receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have INR/PT within the therapeutic range as deemed appropriate by the investigator
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by either an echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Step 1 enrollment
* Corrected QT interval (QTc) prolongation to \< 480 ms based on average triplicate 12-lead electrocardiogram (ECG)
* Pulse oximetry \> 93% on room air
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5) resulting from prior chemotherapy, surgery, and/or radiation must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment are eligible
* All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
* Pregnant, planning to become pregnant, or breast-feeding women will not be entered on this study. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Abstinence is an acceptable method of birth control
* Methods considered as highly effective methods of contraception include:
* Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
* Oral
* Intravaginal
* Transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation:
* Oral
* Injectable
* Implantable
* Intrauterine device (IUD)
* Intrauterine hormone-releasing system (IUS)
* Bilateral tubal occlusion
* Vasectomized partner
* Complete sexual abstinence defined as refraining from heterosexual intercourse. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception
* Non-child-bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle-stimulating hormone \[FSH\] \> 40 mIU/mL and estradiol \< 40 pg/mL \[\< 147 pmol/L\] is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method
* Male patients must not freeze or donate sperm starting at enrollment and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrolment in this study
* Female patients must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are receiving chloroquine or hydroxychloroquine within 14 days are not eligible for this trial
* Patients who received a live, attenuated vaccine (messenger ribonucleic acid \[mRNA\] and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to enrollment are not eligible for this trial
* Note: Participants, if enrolled, should not receive live vaccines during the study and up to 90 days after the last dose of study intervention. It is recommended that patients receive a yearly influenza killed vaccination and additional killed vaccinations based on local or national recommendations. Consider vaccination against viral pathogens that cause pneumonias according to local or national guidelines
* Patients who have received a prior solid organ transplantation are not eligible
* Patients with a medical history of myocardial infarction within 180 days before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV) or troponin levels consistent with myocardial infarction as defined according to the manufacturer 28 days prior to enrollment are not eligible
* Additionally, patients with a history of any of the following congenital heart disease are not eligible:
* Single ventricle heart defects (hypoplastic left heart syndrome, unbalanced atrioventricular septal defects, double inlet left ventricle, tricuspid atresia, the presence of superior cavopulmonary anastomosis or Fontan palliation);
* Unpalliated defects with significant hemodynamic alterations or palliated lesions with residual hemodynamic alterations (ductal-dependent or shunt-dependent physiology, large unrestrictive ventricular septal defect, transposition of the great arteries, greater than moderate atrioventricular valve insufficiency, moderate or greater aortic valve stenosis, moderate or greater aortic valve insufficiency, large atrial septal defects with significant right ventricular volume overload, large patent ductus arteriosus)
* Patients who have a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART) are not eligible. (Drainage and concentrated ascites reinfusion therapy are not allowed within 2 weeks prior to enrollment)
* Patients who have spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms are not eligible
* Patients with a known history of severe hypersensitivity to DS-8201a, any excipient contained in the DS-8201a drug formulation, or HER2-targeted monoclonal antibodies (trastuzumab, pertuzumab, margetuximab) are not eligible
* Patients who have an uncontrolled infection or non-healing surgical site are not eligible
* Patients with a known history of substance abuse or any other clinically significant medical conditions (i.e. psychological conditions) that may, in the opinion of the investigator, interfere with the patient's participation in the clinical study or evaluation of the clinical study results are not eligible
* Patients who have pulmonary compromise, ex hypoxia, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.), or prior pneumonectomy are not eligible
* Patients who have a history of (non-infectious) ILD (interstitial lung disease)/pneumonitis that required steroids, has current ILD/pneumonitis, or for whom suspected ILD/pneumonitis cannot be ruled out by imaging at screening are not eligible. Patients who have history of genetic disorders of the lung (i.e. cystic fibrosis are not eligible)
* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study are not eligible
* Patients with known hepatitis B or C with detectable viral load are not eligible
* Patients with any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of enrollment or genetic diseases involving the lung are not eligible
* Patients with an active primary immunodeficiency are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Trastuzumab Deruxtecan
Desmoplastic Small Round Cell Tumor, Osteosarcoma, Recurrent Desmoplastic Small Round Cell Tumor, Recurrent Kidney Wilms Tumor, Recurrent Osteosarcoma, Refractory Desmoplastic Small Round Cell Tumor, Refractory Wilms Tumor, Wilms Tumor, Bones and Joints
Children’s Health
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
ALL
18 Years and over
PHASE3
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 Clear Cell Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) 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. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Wickiser
ALL
up to 30 Years old
PHASE2
NCT04322318
STU-2020-1103
Inclusion Criteria:
* Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on APEC14B1, consented to Part A - Eligibility Screening, and have received an initial stratum assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a final stratum assignment showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on APEC14B1 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
* Patients must be =\< 30 years old at study enrollment
* Patients with the following diagnoses are eligible for this study:
* Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
* Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
* Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
* High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
* Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations
* Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
* Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
* Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
* Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
* Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
* Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the initial stratum assignment on APEC14B1-REN
* Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
* Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
* Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, 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
* Radiation therapy (RT): \>= 2 weeks (wks) must have elapsed 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. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
* Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (performed within 7 days prior to enrollment)
* Platelet count \>= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (performed within 7 days prior to enrollment)
* Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
* Creatinine clearance or radioisotope GFR \>= 60 mL/min/1.73 m\^2 (performed within 7 days prior to enrollment)
* Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR \>= 60 mL/min/1.73 m\^2), or an adequate serum creatinine as per the following table:
* Age: Maximum Serum Creatinine (mg/dL)
* 1 month to \< 6 months: 0.4 (male and female)
* 6 months to \< 1 year: 0.5 (male and female)
* 1 to \< 2 years: 0.6 (male and female)
* 2 to \< 6 years: 0.8 (male and female)
* 6 to \< 10 years: 1 (male and female)
* 10 to \< 13 years: 1.2 (male and female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =\< ULN for patients whose total bilirubin \> 1.5 x ULN (performed within 7 days prior to enrollment)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age or =\< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)
Exclusion Criteria:
* Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
* Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
* For patients with high-risk or very high-risk relapsed FHWT:
* Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate \< 16 mmol/L and serum phosphate =\< 2 mg/dL (or \< 0.8 mmol/L) without supplementation
* For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
* Chronic inflammatory bowel disease and/or bowel obstruction
* Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating 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 PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Ifosfamide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, PROCEDURE: Surgical Procedure, DRUG: Topotecan, PROCEDURE: Transabdominal Ultrasound, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Anaplastic Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Kidney
Children’s Health
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT03866382
STU-2019-1012
Inclusion Criteria:
* Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
* One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
* One bone lesion on bone scan (tec99 or sodium fluoride \[NaF\] PET/CT, CT or MRI) for the bone-only cohort.
* Histologically confirmed diagnosis of one of the following metastatic cohorts:
* Small cell/ neuroendocrine carcinoma of the bladder (Cohort A)- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
* Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma (Cohort B) - must be pure (per World Health Organization \[WHO\] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma
* Squamous cell carcinoma of the bladder (Cohort C) - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
* Plasmacytoid urothelial carcinoma (Cohort D) - Tumor should show predominantly \> or equal \~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
* Any penile cancer (Cohort E)
* Sarcomatoid renal cell carcinoma (Cohort F) - Tumor should be predominantly sarcomatoid \~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed
* Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to (Cohort G) : Micropapillary (Tumor should show predominantly \> or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly \> or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC
* Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
* Sarcomatoid urothelial carcinoma (Cohort H) - Tumor should show predominantly \~ 50% sarcomatoid differentiation
* Renal medullary carcinoma (Cohort I) - Per World Health Organization (WHO) definition, ideally confirmed with immunostains
* Bone-only metastatic GU tumors (non-prostate) (Cohort J) - All genitourinary histologies, except prostate are eligible
* Renal Collecting Duct Carcinoma (Cohort K) - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)
* Urethra carcinoma (Cohort L) - May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
* H\&E slides from diagnostic tumor tissue for retrospective central pathology review
* Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
* Age \>= 18 years
* Patients must be able to swallow oral formulation of the tablets
* Karnofsky performance status \>= 80%
* Absolute neutrophil count (ANC) \>= 1,000/mcL
* Platelet count \>= 75,000/mcL
* Total bilirubin =\< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =\< 3.0 mg/dL
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) (or =\< 5 x ULN for patients with liver metastases or Gilbert's disease)
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 40 mL/min/1.73 m\^2 (calculated using the Chronic Kidney Disease Epidemiology \[CKD-EPI\] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
* Hemoglobin \>= 9 g/dL (transfusion of packed red blood cells \[PRBCs\] allowed)
* Serum albumin \>= 3.2 g/dL
* Lipase and amylase =\< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
* Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
* No prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors with the exception of patients with "urothelial carcinoma" histology (cohorts D, H, J, L)
* Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
* Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
* Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil \[PTU\] or methimazole) including physiologic oral corticosteroids are eligible
* Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
* Women of childbearing potential must have a negative pregnancy test =\< 7 days prior to registration
* Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea \>= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
* Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
* The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
* The patient has received no radiation therapy:
* To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
* To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
* To any other site(s) within 2 weeks before the first dose of study treatment
* The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
* The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
* The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
* The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
* The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
* The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
* No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=\< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
* No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
* Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* The patient has not experienced any of the following:
* Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
* Hemoptysis of \>= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
* Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
* The patient has no tumor invading any major blood vessels
* The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible
* The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
* Cardiovascular disorders including:
* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic, or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
* The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms within 28 days before randomization. Note: if initial QTcF is found to be \> 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =\< 500 ms, the subject meets eligibility in this regard
* Any history of congenital long QT syndrome
* Any of the following within 6 months before registration of study treatment:
* Unstable angina pectoris
* Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
* Stroke (including transient ischemic attack \[TIA\], or other ischemic event)
* Myocardial infarction
* Cardiomyopathy
* No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
* Any of the following that have not resolved within 28 days before the first dose of study treatment:
* Active peptic ulcer disease
* Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
* None of the following within 2 years before the first dose of study treatment:
* Abdominal fistula or genitourinary fistula
* Gastrointestinal perforation
* Bowel obstruction or gastric outlet obstruction
* Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
* Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
* No other clinically significant disorders such as:
* Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
* Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
* History of organ or allogeneic stem cell transplant
* Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone \[TSH\], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
* No history of major surgery as follows:
* Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
* Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement
* Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
* No history of severe hypersensitivity reaction to any monoclonal antibody
* No evidence of active malignancy, requiring systemic treatment within 2 years of registration
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
* No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative
* No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, BIOLOGICAL: Ipilimumab, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma, Bladder Mixed Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Bladder Squamous Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Collecting Duct Carcinoma, Invasive Bladder Giant Cell Urothelial Carcinoma, Invasive Bladder Lymphoepithelioma-Like Carcinoma, Invasive Bladder Nested Urothelial Carcinoma, Invasive Bladder Plasmacytoid Urothelial Carcinoma, Invasive Bladder Sarcomatoid Urothelial Carcinoma, Invasive Bladder Urothelial Carcinoma, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Malignant Testicular Leydig Cell Tumor, Malignant Testicular Sertoli Cell Tumor, Metastatic Bladder Carcinoma, Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma, Metastatic Bladder Giant Cell Urothelial Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Lipid-Rich Urothelial Carcinoma, Metastatic Bladder Micropapillary Urothelial Carcinoma, Metastatic Bladder Plasmacytoid Urothelial Carcinoma, Metastatic Bladder Sarcomatoid Urothelial Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Chromophobe Renal Cell Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Papillary Renal Cell Carcinoma, Metastatic Penile Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Metastatic Urethral Carcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IV Urethral Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Urachal Adenocarcinoma, Urethral Clear Cell Adenocarcinoma, Kidney, Other Male Genital, Other Urinary, Urinary Bladder
UT Southwestern
Testing an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO
This phase Ib trial studies the side effects of nivolumab and to see how well it works alone and in combination with other treatments, such as ipilimumab, cabozantinib, platinum containing therapy, and fluoropyrimidine, in treating patients with autoimmune disorders and cancer that has spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced), to other places in the body (metastatic) or cannot removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib blocks certain proteins, which may help keep tumor cells from growing. It may also prevent the growth of new blood vessels that tumors need to grow. Cabozantinib is a type of tyrosine kinase inhibitor and a type of angiogenesis inhibitor. Chemotherapy drugs, such as platinum containing therapies and fluoropyrimidine, 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 alone and in combination with other treatments, including ipilimumab, cabozantinib, platinum containing therapy, or fluoropyrimidine, may be safe, tolerable, and/or effective in treating patients with autoimmune disorders and advanced, metastatic, or unresectable cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT03816345
STU-2021-0100
Inclusion Criteria:
* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting, as well as the neoadjuvant or perioperative setting in which such treatment is considered standard of care or has been approved. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab or other PD1/PD-L1 inhibitors are FDA-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)
* Patients enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* Patients enrolled on the study can receive Nivolumab with other FDA-approved combinations according to the FDA package insert, including, but not limited to ipilimumab, cabozantinib or chemotherapy
* Patients who have previously received other forms of immunotherapy (high-dose \[HD\] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks
* Age \>= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* Creatinine ULN OR glomerular filtration rate (GFR) \>= 30 mL/min (if using the Cockcroft-Gault formula)
* Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
* If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
* If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
* Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
* The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product
* Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
* WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy), tubal ligation, or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
* These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
* Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately. Patients can resume treatment upon termination of a pregnancy or the completion of a successful pregnancy
* Ability to understand and the willingness to sign a written informed consent document
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort (Please note: Patients with more than one autoimmune disease should receive assessments for all previously diagnosed autoimmune diseases. For example, a patient with psoriasis and IBD might be enrolled in the IBD cohort. Disease assessments for both psoriasis and IBD should be obtained, as per protocol. Case report forms \[CRFs\] for all relevant autoimmune diseases should be utilized. However, all additional cohort requirements will be considered optional and only the assessments from the assigned cohort will be considered mandatory)
* DM/SSc-SPECIFIC INCLUSION: Patients with known SSc or DM according to updated classification criteria (Van den Hoogan et al., Arthritis Rheum 2013;65(11):2737-47; Lundberg et al., A\&R in press). Overlap features are permitted, but patients must meet criteria for a "primary diagnosis" of DM or SSc
* DM/SSc-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for DM or SSc unless specifically excluded
* DM/SSc-SPECIFIC INCLUSION: Patients must have a baseline computed tomography (CT) of the chest (within 6 months of study entry)
* RA-SPECIFIC INCLUSION: Rheumatologist-diagnosed RA requiring prior treatment with disease-modifying antirheumatic drugs (DMARDs) before patient was diagnosed with current malignancy. We recommend, but do not require, documentation for meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
* RA-SPECIFIC INCLUSION: Prednisone up to 10 mg/day will be allowed. Intraarticular steroids will be allowed for the treatment of new symptomatic joints
* RA-SPECIFIC INCLUSION: Nonsteroidal anti-inflammatory drugs (NSAIDs) will be allowed
* SLE-SPECIFIC INCLUSION: SLE diagnosed by a rheumatologist. The patient should meet the revised 1997 American College of Rheumatology (ACR) classification criteria for SLE, but this is not mandatory
* ULCERATIVE COLITIS (UC)-SPECIFIC INCLUSION: Diagnosis of UC must be made by endoscopy with biopsies
* UC-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* UC-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (antigen \[Ag\] negative, antibody \[core (c)Ab\] negative, antibody \[surface (s)Ab\] positive or negative) and Mycobacterium tuberculosis (purified-protein- derivative \[PPD\] or enzyme-linked immunospot assay \[ELISpot or T-spot\]) or be on appropriate anti-microbial treatment for these infections
* UC-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission, defined as a Mayo Clinic score (MCS) of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 either without medications, or treated with 5-ASA derivative, probiotic, or prior fecal transplant
* UC-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on 6-mercaptopurine, azathioprine, methotrexate, or rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* UC-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either be A) in clinical remission, defined as a MCS of 2 or lower and no subscore higher than 1, and an endoscopic subscore of 0 or 1 on a biologic therapy targeting tumor necrosis alpha (TNF-α) (infliximab, adalimumab, golimumab, or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), IL-23p19 inhibitors (risankizumab or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease defined as a MCS of 3-5 and no subscore higher than 2, and an endoscopic subscore of \< 2 on one of the medications or combination of medications defined for the Moderate or Mild cohort
* CROHN'S DISEASE (CD)-SPECIFIC INCLUSION: Complete colonoscopy with biopsies during study screening, within 8 weeks before initial nivolumab administration, or within 4 weeks after initial nivolumab administration
* CD-SPECIFIC INCLUSION: If patients have prior known disease in the stomach or small intestines, appropriate endoscopic evaluation (esophagogastroduodenoscopy/video capsule endoscopy) and/or imaging (computed tomography or magnetic resonance enterography) must also be current within 4 weeks prior to nivolumab administration
* CD-SPECIFIC INCLUSION: Deep enteroscopy techniques, such as double balloon enteroscopy, will not be required
* CD-SPECIFIC INCLUSION: Patients must test negative for hepatitis B (sAg negative, cAb negative, sAb positive or negative) and M. tuberculosis (PPD or ELISpot or T-spot) or be on appropriate anti-microbial treatment for these infections
* CD-SPECIFIC INCLUSION: Mild Disease Cohort: Patients must be in clinical remission as defined by a Crohn's Disease Activity Index (CDAI) \< 150 either without treatment or on a 5-ASA derivative, probiotic, antibiotics, or following fecal transplant
* CD-SPECIFIC INCLUSION: Moderate Disease Cohort: Patients must be in clinical remission as defined by a CDAI \< 150 on 6-mercaptopurine, azathioprine, methotrexate, rectal hydrocortisone, budesonide, or one of these medications in combination with any of the medications listed in the Mild cohort
* CD-SPECIFIC INCLUSION: Severe Disease Cohort (A or B): Patients must either A) be in clinical remission as defined by a CDAI \< 150 on biologic therapy targeting TNF-α (infliximab, adalimumab, certolizumab pegol, or other approved agent in this class), IL-12/23p40 (Ustekinumab or other approved agent in this class), α4β7 integrin (vedolizumab or other approved agent in this class), selective JAK1 inhibitor (upadacitinib or other approved agent in this class), selective sphingosine 1-phosphate receptor (S1PR) inhibitors (ozanimod, etrasimod or other approved agent in this class), or one of these biologic therapies in combination with any of the medications listed in the Mild or Moderate cohort, or B) have mild active disease as defined by a CDAI of 150 to 220 on one of medications or combination of medications defined for the Moderate or Mild cohort
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For other autoimmune diseases that cannot be classified, the eligibility criteria will be determined by the managing rheumatologist or other autoimmune disease specialist, based on the clinical judgement and current American College of Radiology (ACR) classification guidelines or other relevant guidelines, as per the disease category in question
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For giant cell arteritis (GCA), patients must have had positive temporal artery biopsy for GCA and abnormal erythrocyte sedimentation rate (ESR) at time of diagnosis
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: For polymyalgia rheumatica (PMR), patients must have clinical diagnosis in addition to elevated inflammatory markers including (ESR, C reactive protein \[CRP\])
* OTHER AUTOIMMUNE DISEASES- NS-SPECIFIC INCLUSION: Patients can be in remission (with no glucocorticoids or immunosuppressive medications) or have low-moderate activity, which is defined as being on prednisone ≤ 10 mg or equivalent
* MS-SPECIFIC INCLUSION: Patients must meet 2017 McDonald criteria for the diagnosis of MS (Thompson AJ, et al. Diagnosis of multiple sclerosis: 2017 revision of the McDonald criteria. Lancet Neurol. 17(2):162-173.)
* MS-SPECIFIC INCLUSION: Patients with MS can be in remission and can have a history of being on immunomodulatory agents, but at the time of entry into the clinical trial, patients should be off any concurrent MS therapy for at least 2 weeks. Patients can resume concurrent MS therapy 2 weeks after Nivolumab initiation. Patients in the MS2 cohort may be receiving contemporary multiple sclerosis disease modifying therapies, including but not limited to anti CD20 agents (ocrelizumab, rituximab, ofatumumab, ublituximab), sphingosine 1 phosphate (S1P) modulators (fingolimod, siponimod, ozanimod, ponesimod), cladribine, or other FDA approved MS therapies
* MS-SPECIFIC INCLUSION: Patients must have neurologic stability for at least 4 weeks prior to nivolumab initiation
* SJS-SPECIFIC INCLUSION: SjS diagnosed by a rheumatologist or oral medicine provider. The patient should meet the American-European Consensus Criteria for Sjögren's Syndrome (Vitali, et al., 2002). If on treatment, the patient may only be on hydroxychloroquine and prednisone ≤ 10 mg or equivalent
* PSO/PSA-SPECIFIC INCLUSION: Patients with known PsO as diagnosed by a dermatologist or PsA by a rheumatologist and/or by Classification for Psoriatic Arthritis (CASPAR) criteria (Tillett et al., 2012)
* PSO/PSA-SPECIFIC INCLUSION: Patients must have stable disease as determined by the investigator with no change in systemic therapy and/or biologic therapy for at least 3 months, except for those on tumor necrosis factor (TNF) inhibitors. In the case of TNF inhibition, patients may have transitioned to an alternative biologic therapy with stable disease for at least 4 weeks. For PsA, no change in corticosteroid therapy for at least 1 month prior to baseline and dose must be 10 mg or less
* PSO/PSA-SPECIFIC INCLUSION: Patients may be on any concurrent therapy for PsO or PsA unless specifically excluded
Exclusion Criteria:
* Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted (2 week washout from start of treatment), if all of the following criteria are met:
* Repeat imaging demonstrates no new sites of bone metastases
* The lesion being considered for palliative radiation is not a target lesion
* Patients with prior therapy with an anti-PD-1 or anti-PD-L1
* Patients with prior allogeneic hematologic transplant
* Patients who are receiving any other anticancer investigational agents
* 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 would limit compliance with study requirements
* Patients with thymoma concurrent with myasthenia gravis
* UC-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* UC-SPECIFIC EXCLUSION: Prior colectomy
* UC-SPECIFIC EXCLUSION: Concurrent primary sclerosing cholangitis (PSC). Patients with PSC can be enrolled on the Other Autoimmune Diseases Cohorts
* UC-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* CD-SPECIFIC EXCLUSION: Known untreated abscesses, untreated and symptomatic strictures, short gut physiology, or isolated jejunal disease
* CD-SPECIFIC EXCLUSION: Patients who have received ipilimumab treatment
* CD-SPECIFIC EXCLUSION: Patients on empiric immunosuppressive treatment without any clinical workup
* MS-SPECIFIC EXCLUSION: Patients with MS cannot have medical contraindications to gadolinium-enhanced magnetic resonance imaging (MRI) PROCEDURE: Biospecimen Collection, DRUG: Cabozantinib, DRUG: Fluoropyrimidine, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab, DRUG: Platinum Compound, DRUG: Platinum Doublet
Autoimmune Disease, Crohn Disease, Dermatomyositis, Hematopoietic and Lymphoid Cell Neoplasm, Inflammatory Bowel Disease, Malignant Solid Neoplasm, Multiple Sclerosis, Psoriasis, Psoriatic Arthritis, Rheumatoid Arthritis, Sjogren Syndrome, Systemic Lupus Erythematosus, Systemic Scleroderma, Ulcerative Colitis, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Leukemia, Not Otherwise Specified, Leukemia, Other, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Lymphoid Leukemia, Lymphoma, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
A Phase 3 Study of Tabelecleucel for Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease After Failure With Rituximab or Rituximab and Chemotherapy (ALLELE)
The purpose of this study is to determine the clinical benefit and characterize the safety profile of tabelecleucel for the treatment of Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD) in the setting of (1) solid organ transplant (SOT) after failure of rituximab (SOT-R) and rituximab plus chemotherapy (SOT-R+C) or (2) allogeneic hematopoietic cell transplant (HCT) after failure of rituximab.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tamra Slone
ALL
Not specified
PHASE3
NCT03394365
STU-2018-0349
Inclusion Criteria:
• Prior SOT of kidney, liver, heart, lung, pancreas, small bowel, or any combination of these (C-SOT); or prior allogeneic HCT (C-HCT).
• A diagnosis of locally assessed, biopsy-proven EBV+ PTLD.
• Availability of appropriate partially HLA-matched and restricted tabelecleucel has been confirmed by the sponsor.
• Measurable, 18F-deoxyglucose (FDG)-avid (Deauville score ≥ 3) systemic disease using Lugano Classification response criteria by positron emission tomography (PET)-diagnostic computed tomography (CT), except when contraindicated or mandated by local practice, then magnetic resonance imaging (MRI) may be used. For participants with treated central nervous system (CNS) disease, a head CT and/or brain/spinal MRI as clinically appropriate will be required to follow CNS disease response per Lugano Classification response criteria.
• Treatment failure of rituximab or interchangeable commercially available biosimilar monotherapy (C-SOT-R or C-HCT) or rituximab plus any concurrent or sequentially administered chemotherapy regimen (C-SOT-R+C) for treatment of PTLD.
• Males and females of any age.
• Eastern Cooperative Oncology Group performance status ≤ 3 for participants aged ≥ 16 years; Lansky score ≥ 20 for participants \< 16 years.
• For C-HCT only: If allogeneic HCT was performed as treatment for an acute lymphoid or myeloid malignancy, the underlying primary disease for which the participant underwent transplant must be in morphologic remission.
• Adequate organ function.
• Absolute neutrophil count ≥ 1000/μL, (C-SOT) or ≥ 500/μL (C-HCT), with or without cytokine support.
• Platelet count ≥ 50,000/μL, with or without transfusion or cytokine support. For C-HCT, platelet count \< 50,000/μL but ≥ 20,000/μL, with or without transfusion support, is permissible if the participant has not had grade ≥ 2 bleeding in the prior 4 weeks (where grading of the bleeding is determined per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\], version 5.0).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin each \< 5 × the upper limit of normal; however, ALT, AST, and total bilirubin each ≤ 10 × upper limit of normal is acceptable if the elevation is considered by the investigator to be due to EBV and/or PTLD involvement of the liver as long as there is no known evidence of significant liver dysfunction.
• Participant or participant's representative is willing and able to provide written informed consent.
Exclusion Criteria:
• Currently active Burkitt, T-cell, NK/T-cell lymphoma/LPD, Hodgkin, plasmablastic, transformed lymphoma, active hemophagocytic lymphohistiocytosis, or other malignancies requiring systemic therapy.
• Daily steroids of \> 0.5 mg/kg prednisone or glucocorticoid equivalent, ongoing methotrexate, or extracorporeal photopheresis.
• Untreated CNS PTLD or CNS PTLD for which the participant is actively receiving CNS-directed chemotherapy (systemic or intrathecal) or radiotherapy at enrollment. NOTE: Participants with previously treated CNS PTLD may enroll if CNS-directed therapy is complete.
• Suspected or confirmed grade ≥ 2 graft-versus-host disease (GvHD) per the Center for International Blood and Marrow Transplant Research consensus grading system at enrollment.
• Ongoing or recent use of a checkpoint inhibitor agent (eg, ipilimumab, pembrolizumab, nivolumab) within 3 drug half-lives from the most recent dose to enrollment.
• For C-HCT: active adenovirus viremia.
• Need for vasopressor or ventilatory support.
• Antithymocyte globulin or similar anti-T cell antibody therapy ≤ 4 weeks prior to enrollment.
• Treatment with Epstein-Barr virus cytotoxic T lymphocytes or chimeric antigen receptor T cells directed against B cells within 8 weeks of enrollment (C-SOT or C-HCT), or unselected donor lymphocyte infusion within 8 weeks of enrollment (C-HCT only).
• Female who is breastfeeding or pregnant or female of childbearing potential or male with a female partner of childbearing potential unwilling to use a highly effective method of contraception.
• Inability to comply with study-related procedures.
• Any medical condition or organ system dysfunction that in the investigator';s opinion, could compromise the participant's safety or ability to complete the study.
BIOLOGICAL: tabelecleucel
Epstein-Barr Virus+ Associated Post-transplant Lymphoproliferative Disease (EBV+ PTLD), Solid Organ Transplant Complications, Lymphoproliferative Disorders, Allogeneic Hematopoietic Cell Transplant, Stem Cell Transplant Complications, Other
Epstein-Barr Virus (EBV)-associated Lymphoproliferative Disease (LPD), Epstein-Barr Virus (EBV), Cytotoxic T lymphocyte (CTL), Cancer After Transplant, Kidney transplant, Renal transplant, Liver transplant, Heart transplant, Lung transplant, Intestinal transplant, Pancreas transplant, Post-transplant Lymphoma, Solid Organ Transplant (SOT), Bone Marrow Transplant Complications, Epstein-Barr Virus-specific Cytotoxic T Lymphocytes (EBV-CTL), Hematopoietic Cell Transplant (HCT), Hematopoietic Stem Cell Transplantation (HSCT), Allogeneic Hematopoietic Cell Transplant, Allogeneic, Off-The-Shelf T-cell Immunotherapy
Children’s Health
Nephrotic Syndrome Study Network (NEPTUNE)
Minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and Membranous nephropathy (MN), generate an enormous individual and societal financial burden, accounting for approximately 12% of prevalent end stage renal disease (ESRD) cases (2005) at an annual cost in the US of more than $3 billion. However, the clinical classification of these diseases is widely believed to be inadequate by the scientific community. Given the poor understanding of MCD/FSGS and MN biology, it is not surprising that the available therapies are imperfect. The therapies lack a clear biological basis, and as many families have experienced, they are often not beneficial, and in fact may be significantly toxic. Given these observations, it is essential that research be conducted that address these serious obstacles to effectively caring for patients. In response to a request for applications by the National Institutes of Health, Office of Rare Diseases (NIH, ORD) for the creation of Rare Disease Clinical Research Consortia, a number of affiliated universities joined together with The NephCure Foundation the NIDDK, the ORDR, and the University of Michigan in collaboration towards the establishment of a Nephrotic Syndrome (NS) Rare Diseases Clinical Research Consortium. Through this consortium the investigators hope to understand the fundamental biology of these rare diseases and aim to bank long-term observational data and corresponding biological specimens for researchers to access and further enrich.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Bethany.Roehm@UTSouthwestern.edu
Bethany Roehm
All
up to 80 Years old
N/A
NCT01209000
STU 112012-082
Cohort A (biopsy cohort)
• Documented urinary protein excretion ≥1500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.
• Scheduled renal biopsy Cohort B (non-biopsy, cNEPTUNE)
• Age <19 years of age
• Initial presentation with <30 days immunosuppression therapy
• Proteinuria/nephrotic
• UA>2+ and edema OR
• UA>2+ and serum albumin <3 OR
• UPC > 2g/g and serum albumin <3 Exclusion Criteria (Cohort A&B):
• Prior solid organ transplant
• A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
• Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
• Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months
• Unwillingness or inability to give a comprehensive informed consent
• Unwillingness to comply with study procedures and visit schedule
• Institutionalized individuals (e.g., prisoners)
Inclusion Criteria:
Patients presenting with an incipient clinical diagnosis for FSGS/MCD or MN or pediatric
participants not previously biopsied, with a clinical diagnosis for FSGS/MCD or MN meeting
the following inclusion criteria:
• Documented urinary protein excretion ≥1500 mg/24 hours or spot protein: creatinine ratio equivalent at the time of diagnosis or within 3 months of the screening/eligibility visit.
• Scheduled renal biopsy Cohort B (non-biopsy, cNEPTUNE)
Inclusion Criteria:
• Age <19 years of age
• Initial presentation with <30 days immunosuppression therapy
• Proteinuria/nephrotic
• UA>2+ and edema OR
• UA>2+ and serum albumin <3 OR
• UPC > 2g/g and serum albumin <3 Exclusion Criteria (Cohort A&B):
• Prior solid organ transplant
• A clinical diagnosis of glomerulopathy without diagnostic renal biopsy
• Clinical, serological or histological evidence of systemic lupus erythematosus (SLE) as defined by the ARA criteria. Patients with membranous in combination with SLE will be excluded because this entity is well defined within the International Society of Nephrology/Renal Pathology Society categories of lupus nephritis, and frequently overlaps with other classification categories of SLE nephritis (68)
• Clinical or histological evidence of other renal diseases (Alport, Nail Patella, Diabetic Nephropathy, IgA-nephritis, monoclonal gammopathy (multiple myelomas), genito-urinary malformations with vesico-urethral reflux or renal dysplasia)
• Known systemic disease diagnosis at time of enrollment with a life expectancy less than 6 months
• Unwillingness or inability to give a comprehensive informed consent
• Unwillingness to comply with study procedures and visit schedule
• Institutionalized individuals (e.g., prisoners)
Procedure: Kidney Biopsy
Minimal Change Disease (MCD), Membranous Nephropathy, Glomerulosclerosis, Focal Segmental, Kidney
Focal and Segmental Glomerulosclerosis, Focal & Segmental Glomerulosclerosis, Focal Segmental Glomerulosclerosis, FSGS, Minimal change disease, MCD, Membranous Nephropathy, MN, Nephrotic Syndrome, Neph Syndrome, NEPTUNE, NephCure, Halpin
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Phase 1 Dose-escalating Study of MM-398 (Irinotecan Sucrosofate Liposome Injection) Plus Intravenous Cyclophosphamide in Recurrent or Refractory Pediatric Solid Tumors
This is a Phase 1 study of the combination of two drugs: MM-398 and Cyclophosphamide. The goal is to find the highest dose of MM-398 that can be given safely when it is used together with the chemotherapy drug Cyclophosphamide.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Avanthi Shah
All
12 Months to 20 Years old
Phase 1
NCT02013336
STU 092013-007
Inclusion Criteria:
• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
Exclusion Criteria:
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment
Drug: MM-398 (Irinotecan Sucrosofate Liposome Injection) plus cyclophosphamide
Recurrent or Refractory Solid Tumors, Ewing Sarcoma, Rhabdomyosarcoma, Neuroblastoma, Osteosarcoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Eye and Orbit, Gall Bladder, Head and Neck, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Mycosis Fungoides, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Sarcoma, Small Intestine, Soft Tissue, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva
pediatric, MM-398, cyclophosphamide, irinotecan
Children’s Health
Tacrolimus/Everolimus vs. Tacrolimus/MMF in Pediatric Heart Transplant Recipients Using the MATE Score (TEAMMATE)
The TEAMMATE Trial will enroll 210 pediatric heart transplant patients from 25 centers at 6 months post-transplant and follow each patient for 2.5 years. Half of the participants will receive everolimus and low-dose tacrolimus and the other half will receive tacrolimus and mycophenolate mofetil. The trial will determine which treatment is better at reducing the cumulative risk of coronary artery vasculopathy, chronic kidney disease and biopsy proven-acute cellular rejection without an increase in graft loss due to all causes (e.g. infection, PTLD, antibody mediated rejection).
Call 214-648-5005
studyfinder@utsouthwestern.edu, kara.lorduy@childrens.com
Ryan Butts
All
up to 21 Years old
Phase 3
NCT03386539
STU 122017-025
Inclusion Criteria:
• Orthotopic heart transplantation
• Age < 21 years at time of transplant
• Stable immunosuppression at the time of randomization with no contraindication to everolimus, tacrolimus, or mycophenolate mofetil
• Planned follow-up at a study site for the 30 month duration of the study.
• Subject or legal adult representative capable of providing informed consent (in general, assent will be sought for children aged 12 years or older).
Exclusion Criteria:
• Multi-organ transplant (e.g. heart-lung or heart-liver).
• Known hypersensitivity to everolimus, sirolimus, tacrolimus or mycophenolate mofetil (MMF), or to components of the drug products.
• Patients on maintenance corticosteroid therapy exceeding a dose equivalent of prednisone 0.1 mg/kg/day at randomization.
• High-risk for rejection defined as active rejection, recurrent (≥ 2 episodes of grade 2R rejection) cellular rejection, recurrent rejection (≥ 2 episodes of any grade) with hemodynamic compromise, steroid-resistant rejection or unresolved antibody-mediated rejection during the first 6 months post-heart transplant
• Graft dysfunction (LVEF <40% or wedge pressure >22 mmHg or cardiac index <2.2 L/min/m2)
• Stage 4 or 5 CKD (eGFR <30 ml/min/1.73 m2) or moderate proteinuria (urine protein to urine creatinine ratio >0.5 mg/mg).
• Active infection requiring hospitalization or treatment dose medical therapy.
• Patients with ongoing wound healing problems, clinically significant wound infection requiring continued therapy or other severe surgical complication in the opinion of the Site Principal Investigator.
• Fasting Serum Cholesterol ≥300 mg/dL OR greater than or equal to 7.75 mmol/L, AND fasting triglycerides ≥2.5x the upper limit of normal (ULN). Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication, and reduction of serum cholesterol and triglyceride levels to below exclusion ranges is confirmed.
• Uncontrolled diabetes mellitus.
• Diagnosis of post-transplant lymphoproliferative disorder (PTLD) during the first 6 months post-heart transplant.
• History of non-adherence to medical regimens.
• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) and cannot discontinue the treatment
• Patients who are pregnant or breast-feeding or intend to get pregnant during the study period.
Drug: Everolimus, Drug: Tacrolimus, Drug: Mycophenolate Mofetil
Pediatric Heart Transplantation, Immunosuppression, Chronic Kidney Diseases, Cardiac Allograft Vasculopathy, Heart Transplant Failure and Rejection, Post-transplant Lymphoproliferative Disorder, Heart Transplant Infection
heart transplantation, children, everolimus, tacrolimus, mycophenolate mofetil, randomized clinical trial
Children’s Health
A Study To Evaluate The Efficacy And Safety Of Obinutuzumab In Patients With ISN/RPS 2003 Class III Or IV Lupus Nephritis (REGENCY)
This study will evaluate the efficacy, safety, and pharmacokinetics of obinutuzumab compared with placebo in patients with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis (LN) when added on to standard-of-care therapy consisting of mycophenolate mofetil (MMF) and corticosteroids.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Nazeem.Mohammed@UTSouthwestern.edu
David Karp
All
18 Years to 75 Years old
Phase 3
NCT04221477
STU-2020-0374
Key
• Diagnosis of ISN/RPS 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
• Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour collection
• Other inclusion criteria may apply Key
• Pregnancy or breastfeeding
• Severe renal impairment or the need for dialysis or renal transplantation
• Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
• Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply
Inclusion Criteria:
• Diagnosis of ISN/RPS 2003 Class III or IV LN as evidenced by renal biopsy performed within 6 months. Participants may co-exhibit Class V disease in addition to either Class III or Class IV disease
• Urine protein to creatinine ratio greater than or equal to (>/=) 1 on a 24-hour collection
• Other inclusion criteria may apply Key
Exclusion Criteria:
• Pregnancy or breastfeeding
• Severe renal impairment or the need for dialysis or renal transplantation
• Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to screening or during screening; or cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
• Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
• Known active infection of any kind or recent major episode of infection
• Intolerance or contraindication to study therapies
• Other exclusion criteria may apply
Drug: Obinutuzumab, Drug: MMF, Drug: Prednisone, Drug: Placebo, Drug: Methylprednisolone, Drug: Acetaminophen, Drug: Diphenhydramine
Lupus Nephritis
UT Southwestern; Parkland Health & Hospital System
Abatacept in Immune Checkpoint Inhibitor Myocarditis (ATRIUM)
The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vlad Zaha
All
18 Years and over
Phase 3
NCT05335928
STU-2022-0624
Inclusion Criteria:
• Must have provided informed consent in a manner approved by the Investigator's Institutional Review Board (IRB) prior to any study-related procedure being performed. If a participant is unable to provide informed consent due to his/her medical condition, the participant's legally authorized representative may consent on behalf of the study participant, as permitted by local law and institutional Standard Operating Procedures;
• Aged greater than or equal to 18 years at the time of informed consent;
• Recent use of an FDA-approved immune checkpoint inhibitor (ICI, defined as administered an immune checkpoint inhibitor ≤ 6 months of myocarditis diagnosis), alone or in combination with other cancer therapies (i.e. chemotherapy, radiation therapy or targeted therapy). The FDA-approved ICI could be given as part of a clinical trial but not in combination with a new investigational agent which may cause myocarditis;
• A diagnosis of myocarditis.
• Hospitalized at the time of randomization;
• On 1000 mg of solumedrol per day for myocarditis or with an intent to initiate 1000 mg of solumedrol per day for myocarditis within 24 hours of first administration of study drug;
• Serum evidence of ongoing myocardial injury: Serum evidence of ongoing myocardial injury will be defined as an institutional troponin (either conventional or high-sensitivity troponin I or T, using the standard institutional assay) with a value that is ≥5 times the upper limit of the reference standard normal for that institution. The troponin assay may be adjusted based on sex depending on institutional standards. This value of troponin of ≥5 times above the institutional upper limits of normal value must be noted within 10 days prior to potential randomization. The 10-day period can be in the outpatient or inpatient setting. For example, a participant with a troponin value that on one occasion was ≥5 times the upper limits of institutional normal in the 10-day window prior to potential randomization (whether in the inpatient or outpatient setting), but later decreases below that threshold, typically due to starting corticosteroids, would still be considered eligible;
• The following laboratory parameters, not older than 48 hours at the time of randomization, and measured as part of usual care:
• Total white blood cell (WBC) count >2,500/μl
• Absolute neutrophil count (ANC) >1,500/μL
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <20 times the upper limit of the institutional normal ranges;
• Women of childbearing potential (i.e., not postmenopausal, or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test prior to randomization. Participating women of childbearing potential must be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug. Participating men must also be willing to consistently use effective methods of contraception from screening until at least 90 days after administration of the last dose of study drug; and
• Must be willing and able to abide by all study requirements and restrictions.
Exclusion Criteria:
• Must not have experienced any of the following (as defined in the section on the primary endpoint) in the 30-day period prior to randomization:
• A sudden cardiac arrest
• Cardiogenic shock as defined. A significant bradyarrhythmia (Mobitz type II second degree atrioventricular block or third degree (complete) atrio-ventricular (AV) block, for which an intervention with a temporary or permanent pacemaker is completed or recommended).
• A significant tachyarrhythmia (ventricular fibrillation of any duration or sustained ventricular tachycardia (>30 seconds, >120 beats per minute); or a ventricular tachyarrhythmia requiring intervention.
• Recent (≤2 month) exposure to abatacept or belatacept.
• Concurrent or recent (≤2 month) use of the following non-corticosteroid immunosuppressive therapies prior to randomization: mycophenolate, JAK STAT inhibitors (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib), tacrolimus, anti-thymocyte globulin, alemtuzumab, infliximab, and plasma exchange. The use of intravenous immunoglobulin is permitted prior to randomization and during study treatment.
• Currently enrolled in another interventional study utilizing systemic agents for the management of ICI-related toxicities.
• Female who is pregnant, breastfeeding, or is considering becoming pregnant during the study or for approximately 90 days after the last dose of study drug.
• Male who is considering fathering a child or donating sperm during the study or for approximately 30 days after the last dose of study drug.
• Any active, chronic, or recurrent viral infection that, based on the investigator's clinical assessment, makes the participant an unsuitable candidate for the study. These may include hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, and disseminated (even a single episode) herpes simplex. Active HBV and HCV are defined as: HBV: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for Hepatitis B core antibody (HBc Ab) positive (+) participants; HCV: HCV ribonucleic acid (RNA) detectable in any participant with anti-HCV antibody (HCV Ab). Patients with active Covid-19 infection will be excluded. This is defined as the period of ongoing symptoms in the setting of a positive Covid-19 test, or until 10 days after symptom onset and after resolution of fever for at least 24 hours, without the use of fever-reducing medications.
• Known active tuberculosis (TB), history of incompletely treated TB, suspected or known extrapulmonary TB, suspected or known systemic bacterial or fungal infections;
• Receipt of any live vaccine within four weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 90 days after the last dose of IV study drug.
• Any medical condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would, in the opinion of the Investigator, increase the risk of the participant by participating in the study.
• Any factors that, in the Investigator's opinion, are likely to interfere with study procedures, such as history of noncompliance with scheduled appointments.
Drug: Abatacept plus, Drug: Placebo
Myocarditis Acute, Cancer, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Immune checkpoint Inhibitor, Myocarditis, Abatacept, Immune therapy, Immune related adverse events
UT Southwestern