Rare Genitourinary Cancer Trials

This phase II trial studies how well cabozantinib (Cabometyx, a type of targeted therapy) works in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) in treating patients with rare genitourinary (GU) tumors that have spread 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. All participants will receive treatment: Treatment (cabozantinib, nivolumab, ipilimumab) Patients will take cabozantinib orally (PO) QD on days 1-21 of cycles 1-4, and on days 1-28 of subsequent cycles. Patients also receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Patients then receive nivolumab IV over 30 minutes on day 1 of subsequent cycles. Treatment repeats every 21 days for cycles 1-4 and every 28 days for subsequent cycles for 2 years.

This study is being done to see if a drug called disitamab vedotin (a type of targeted therapy), alone or with pembrolizumab (Keytruda, a type of immunotherapy), works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants. Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic). It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease. All patients will receive treatment with either: Disitamab vedotin alone: Given into the vein (IV; intravenous) every 2 weeks OR Disitamab vedotin + pembrolizumab: Disitamab vedotin is given into the vein (IV; intravenous) every 2 weeks + Pembrolizumab given by IV on Day 1 of each 6-week cycle.

Tumors in the genitourinary tracts can occur in the kidney, bladder, prostate, and testicles and can have common and rare histologies. Some cancers that occur along the genitourinary (GU) tract are rare. Some GU tumors are so rare that they are not included in treatment studies or tissue banks. This makes it hard for researchers to determine standards of care. Researchers want to learn more about common and rare GU tumors. The objective of this study is to learn more about urinary tract cancers. Rare histological variants of the GU tract include bladder/urachal adenocarcinoma, squamous cell carcinoma, and small cell carcinoma; variants of urothelial carcinoma including plasmacytoid, sarcomatoid; renal tumors including sarcomatoid renal cell carcinoma and renal medullary carcinoma; penile cancers; micropapillary, giant cell, lipid rich, clear cell and nested variants, large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns; small cell neuroendocrine carcinoma of the prostate, testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC. Some GU tumors occur so infrequently that they are not systematically captured by currently available registries, treatment protocols or tissue banks. The rarity of these tumors limits the sufficient numbers of patients needed in larger randomized clinical studies to characterize standard treatments or disease course. Systematic and longitudinal collection and annotation of clinical history, tissue samples, imaging studies, participant reported outcomes, and other pertinent information in participants with these rare tumors will yield future knowledge and help with the development of subsequent prospective studies to optimize diagnosis and treatment paradigms for less common GU tumors. There is no treatment given as part of this study. This will be a long-term study to comprehensively study participants with rare GU tumors. Medical history will be collected, and participants followed throughout the course of their illnesses, with particular attention to patterns of disease presentation, recurrence and progression, response to therapies, duration of responses and participant reported outcomes. Tissue samples and blood will be obtained from participants during this study. A broad spectrum of scientific experiments, including genomics and immune monitoring will be performed.

This is a single arm, Phase II trial involving the use of atezolizumab (Tecentriq, a type of immunotherapy) plus platinum (a type of chemotherapy) and etoposide (a type of chemotherapy) for patients with locally advanced urothelial cancer. The primary goal of this trial is to assess the pathologic complete response rate (meaning there is no longer any cancer visible on imaging scans) at time of cystectomy (the surgical removal of the bladder) in patients after being treated with a combination therapy of atezolizumab, platinum, and etoposide. The study population will include male and female patients over the age of 18 with invasive small cell / neuroendocrine carcinoma of the bladder, with or without urothelial cancer component, who are eligible for platinum based chemotherapy and immunotherapy. All patients will be fit to undergo surgical resection of their cancer by cystectomy. This study has 1 treatment arm: Atezolizumab with Platinum and Etoposide, followed by cystectomy. Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 mg on Day 1 of every 21 day cycle (1 cycle = 21 days), with chemotherapy, for 4 cycles. Following cystectomy, Atezolizumab maintenance will continue once every 21 days for up to 1 year. Chemotherapy will include Etoposide given IV on Days 1 - 3 every cycle for the first 4 cycles. Chemotherapy will include either Carboplatin given IV on Day 1 every cycle for the first 4 cycles OR Cisplatin given IV on Day 1 every cycle for first 4 cycles. Cystectomy should be performed within 42 days after completion of last administered study therapy of induction phase (first 4 cycles of chemotherapy). Cystectomy should be performed within 42 days after completion of last administered study therapy (after the first 4 cycles of Atezolizumab + chemotherapy).

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 (a type of targeted therapy). LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse. This study has 2 potential treatment arms: Arm A: LOXO-435 alone LOXO-435 will be administered orally (by mouth, PO) at various dosages. Dosage will be provided by the treatment team. Arm B: LOXO-435 + Pembrolizumab (Keytruda, a type of immunotherapy) LOXO-435 administered orally in combination with pembrolizumab administered intravenously (IV). Dosage and dosing schedule will be provided by the treatment team.

Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs enfortumab vedotin (EV, a type of targeted therapy) and pembrolizumab (Keytruda, a type of immunotherapy), has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers. The objective of this study is to test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract. This study has 2 treatment arms: Arm A: Enfortumab vedotin (EV) EV is administered intravenously (IV) at 1.25 mg/kg. Dosing schedule will be provided by treatment team. Arm B: Pembrolizumab + Enfortumab vedotin (EV) Pembrolizumab is administered IV at 200 mg on day 1 of each 21-day cycle. EV is administered intravenously (IV) at 1.25 mg/kg. Dosing schedule will be provided by treatment team.

Rare tumors of the genitourinary (GU) tract can appear in the kidney, bladder, ureters, and penis. Rare tumors are difficult to study because there are not enough people to conduct large trials for new treatments. Two drugs, sacituzumab govitecan (SG, a type of targeted chemotherapy) and atezolizumab (Tecentriq, a type of immunotherapy), are each approved to treat other cancers. Researchers want to find out if the two drugs used together can help people with rare GU cancers. The objective of this study is to determine clinical effectiveness of sacituzumab govitecan (SG), either alone or in combination with atezolizumab in participants with rare metastatic non-prostate genitourinary tumors. This study has 2 treatment arms: Arm A: Sacituzumab govitecan Sacituzumab govitecan is administered intravenously (IV) at 10 mg/kg on days 1 and 8 of each 21-day cycle. Arm B: Sacituzumab govitecan PLUS Atezolizumab Sacituzumab govitecan is administered intravenously (IV) at 10 mg/kg on days 1 and 8 of each 21-day cycle PLUS Atezolizumab is administered IV at 1200 mg on day 1 each 21-day cycle.

Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin (Zepzelca, a type of chemotherapy) and avelumab (Bavencio, a type of immunotherapy) are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET. The objective of this study is to assess the objective response rate (ORR, how many patients have their cancer shrink in response to taking the study medication) of lurbinectedin, either alone or in combination with avelumab, in participants with small cell carcinoma of the bladder (SCCB) or other high grade neuroendocrine tumors (HGNETs) of the urinary tract. This study has 2 treatment arms: Arm A: Lurbinectedin Lurbinectedin is administered intravenously (IV) over 1 hour on day 1 of each 21-day cycle. Arm B: Lurbinectedin + Avelumab Lurbinectedin is administered intravenously (IV) over 1 hour on day 1 of each 21-day cycle PLUS Avelumab is administered IV at 800 mg over 1 hour on day 1 of each 21-day cycle.

The purpose of this study is to test a new medicine, vepugratinib (a type of targeted therapy), in comparison with placebo, to see if it is safe and can help people with bladder cancer that is advanced or has spread. Vepugratinib or placebo will be administered in combination with enfortumab vedotin (Padcev, a type of targeted therapy) and pembrolizumab (Keytruda, a type of immunotherapy). This study has 2 treatment arms: Arm A: Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion. Dosage and dosing schedule will be provided by the treatment team. Arm B: Placebo + EV + Pembrolizumab Placebo administered orally, and EV + pembrolizumab administered by IV infusion. Dosage and dosing schedule will be provided by the treatment team.

This is a single arm, single site, open-label Phase II study of the effects of oral olaparib (Lynparza, a type of targeted therapy, a PARP inhibitor) in participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L who have had prior treatment with at least one immune checkpoint inhibitor (immunotherapy) or anti-VEGF therapy (targeted therapy). This study has 1 arm: Olaparib: Participants will be initially treated with olaparib 150 mg by mouth (PO) twice daily for one month. After one month of therapy, the dose will be increased to 300mg by mouth twice daily, if tolerated. Treatment will be continued until clinical and/or radiographic progression or unmanageable side effects requiring discontinuation of the drug.

This phase II trial studies the effects of combination therapy with bevacizumab (Avastin, a type of targeted therapy), erlotinib (Tarceva, a type of targeted therapy), and atezolizumab (Tecentriq, a type of immunotherapy) in treating patients with hereditary leiomyomatosis and kidney cancer that has spread to other places in the body (advanced). Bevacizumab is in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumors. This may slow the growth and spread of tumors. Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Combination therapy with bevacizumab, erlotinib, and atezolizumab may stabilize or shrink advanced hereditary leiomyomatosis and kidney cancer. This study has one treatment arm: Bevacizumab + Atezolizumab + Erlotinib Patients receive bevacizumab intravenously (IV) over 30-90 minutes and atezolizumab IV over 30-90 minutes on day 1 of each cycle. Patients also receive erlotinib by mouth (orally or PO) once daily on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

This phase II trial compares the effect of giving cabozantinib (Cabometyx, a type of targeted therapy) with or without cemiplimab (Libtayo, a type of immunotherapy) in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, 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 with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer. This study has 2 treatment arms: Arm A: Cabozantinib alone Patients receive cabozantinib by mouth (orally, PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Upon disease progression, patients may elect to crossover to receive combination therapy on Arm B. Arm B: Cabozantinib + cemiplimab Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 and cabozantinib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity.