Kidney Cancer Trials

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.

This study examines the impact of proton based stereotactic radiation therapy (SBRT) on kidney function as well as other cancer outcomes including local control, locoregional and systemic failure, progression free and overall survival. The incidence of kidney cancer diagnosis has been increasing over the last years. Surgical resection represents the standard treatment. However, many patients are deemed unfit for surgery due to medical comorbidities or technical limitations. There are non-surgical options including active surveillance, cryotherapy, microwave ablation, radiofrequency and stereotactic radiation therapy (SBRT). SBRT using conventional x-rays has recently been shown to improve outcomes for patients with primary renal cell carcinoma (RCC) in terms of local control and toxicity. However, this treatment was associated with a significant decline in kidney function that necessitates additional intervention including dialysis in some patients. Proton therapy represents an emerging technique with unique properties that allow the bulk of the proton cancer fighting energy to be released at the tumor while sparing nearby healthy tissues and organs, particularly the remaining healthy kidney, the remaining part of the affected kidney, bowels, spine and liver. With this technology, both kidneys could be spared and thus less damage is expected. This study aims to study the impact of proton based SBRT on the kidney function. This study has 1 treatment arm (all subjects will receive treatment): Proton Stereotactic Body Radiation therapy (SBRT) Radiation therapy will consist of 3-5 treatments over 1.5 - 2 weeks.

This is a multi-center, single arm open label phase 1b/2 study of pembrolizumab (Keytruda, a type of immunotherapy) in combination with 177Lu-PNT2002 (also known as 177Lu-PSMA I&T), a radiopharmaceutical ( or radiation) therapy in patients with metastatic clear cell renal cell carcinoma (RCC) who have progressed after prior treatment with other immunotherapies. Investigators hypothesize that pembrolizumab in combination with 177Lu-PNT2002 in patients with metastatic clear cell RCC at a biologically active dose will result in tolerable safety profile and it will lead to improved radiological objective responses in patients who have progressed after prior treatment with standard immune-checkpoint inhibitor containing regimens. Patients will have imaging studies to help detect any spread of their cancer. All subjects will receive treatment on this study. Treatment: 177Lu-PNT2002 PLUS Pembrolizumab 177Lu-PNT2002 administered at varying dose levels (to be provided by study team) intravenously (IV) once every 8 weeks PLUS pembrolizumab 400 mg IV once every 6 weeks.

The purpose of the study is to evaluate the progression-free survival (PFS) of casdatifan (a type of targeted therapy) versus placebo when each is given in combination with cabozantinib (Cabometyx, a type of targeted therapy) in adult patients with confirmed advanced or metastatic clear cell Renal Cell Carcinoma who have experienced progression on or after prior immunotherapy. This study has 2 treatment arms: Arm A: Casdatifan PLUS cabozantinib, both taken orally (by mouth, PO). Treatment dose and schedule to be provided by study team. Arm B: Placebo PLUS cabozantinib, both taken orally (by mouth, PO). Treatment dose and schedule to be provided by study 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 III trial compares the effect of adding tivozanib to standard therapy pembrolizumab versus pembrolizumab alone for the treatment of patients with high-risk renal cell carcinoma (RCC). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tivozanib is in a class of medications called kinase inhibitors (a type of targeted therapy). It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving pembrolizumab and tivozanib together may work better than pembrolizumab alone in treating patients with RCC. This study has 2 treatment arms: Arm A: Pembrolizumab Patients receive pembrolizumab intravenously (IV) on days 1 and 43 of each cycle, or on days 1, 22, 43 and 64 of each cycle. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Arm B: Pembrolizumab + tivozanib Patients receive pembrolizumab IV on days 1 and 43 of each cycle and tivozanib by mouth (orally, PO) once daily (QD) on days 1-21, days 29-49, and days 57-77 of each cycle for up to 6 months. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug M9241 triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. This study has 3 treatment arms: Arm A: Treatment with M7824 and deescalating (decreasing) doses of M9241, if appropriate Drug: M7824 1200 mg administered intravenously (IV) in clinic every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously (SC or SQ) every 4 weeks while on M7824 and with or without SBRT Arm B: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with sequential SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241 Arm C: Treatment with M7824 and deescalating doses of M9241 (if appropriate) with concurrent SBRT Drug: M7824 1200 mg administered IV every two weeks while on M9241 and with or without SBRT Drug: M9241 an initial dose of 16.8 mcg/kg administered subcutaneously every 4 weeks while on M7824 and with or without SBRT Radiation: Stereotactic body radiation therapy (SBRT) a fixed dose of 8 Gy x 3 fractions sequential or concurrent with M7824 and M9241

This is a Phase Ib/III, randomized, multicenter, global study evaluating the effectiveness and safety of volrustomig (a type of immunotherapy) in combination with casdatifan (a type of targeted therapy) for the first-line (1L) treatment of participants with advanced clear cell renal cell carcinoma (ccRCC). The primary purpose of this study is to determine the recommended dose of volrustomig and measure the effectiveness and safety of volrustomig in combination with casdatifan compared with nivolumab (Opdivo, a type of immunotherapy) plus ipilimumab (Yervoy, a type of immunotherapy) in participants with advanced ccRCC as first line treatment. This study has 3 potential treatment arms: Arm A: Volrustomig + Casdatifan Volrustomig will be administered as an intravenous (IV) infusion at varying dose levels (to be provided by study team) PLUS Casdatifan administered orally (by mouth, PO). Treatment dose and dosing schedule to be provided by the study team. Arm B: Volrustomig alone Volrustomig will be administered as an intravenous (IV) infusion at varying dose levels (to be provided by study team). Arm C: Nivolumab + Ipilimumab Nivolumab will be administered as an IV infusion PLUS Ipilimumab will be administered as an IV infusion. Doses will be consistent with standard of care, and provided by study team.

This study is a randomized, open label, multicenter Phase II trial to evaluate the effectiveness and safety of botensilimab (a new type of immunotherapy) and balstilimab (a new type of immunotherapy) compared to ipilimumab (Yervoy, a type of immunotherapy) and nivolumab (Opdivo, a type of immunotherapy) in treatment naïve patients with metastatic clear cell renal cell carcinoma (ccRCC). This study has 2 treatment arms: Arm A: botensilimab and balstilimab Subjects will receive 2 cycles of induction treatment with each cycle lasting 6 weeks. Cycle 1 will consist of botensilimab 75mg IV (intravenously) in combination with balstilimab 450mg IV on Day 1 and Day 22. Cycle 2 will consist of balstilimab 450mg IV ONLY on Day 1 and Day 22. Botensilimab will NOT be given in Cycle 2. Subjects will receive 7 cycles of maintenance treatment with each cycle lasting 12 weeks. Cycles 3 and 4 will consist of botensilimab 75mg IV on Day 1 in combination with balstilimab 450mg IV on Day 1, 22, 43 and 64. Cycles 5-9 will consist of balstilimab alone 450 mg IV on Day 1, 22, 43 and 64. Arm B: ipilimumab and nivolumab Subjects will receive 2 cycles of induction treatment with each cycle lasting 6 weeks. Cycle 1 and 2 will consist of ipilimumab 1 mg/kg IV and nivolumab 3 mg/kg on Day 1 and 22. Subjects will receive 7 cycles of maintenance treatment with each cycle lasting 12 weeks. Nivolumab 480mg IV will be given on Day 1, 29 and 57 of each cycle (every 4 weeks).

This phase II trial compares the effect of atezolizumab (Tecentriq, a type of immunotherapy) in combination with usual treatment with cabozantinib (Cabometyx, a type of targeted therapy) to cabozantinib alone in patients with papillary renal cell carcinoma that has spread to other places in the body (metastatic). Immunotherapy, such as atezolizumab, may help body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is a type of targeted therapy that works by blocking the action of an abnormal protein that signals cancer cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of cancer cells. Combination therapy with atezolizumab and cabozantinib may shrink the cancer and allow a longer survival time in patients with metastatic renal cell carcinoma. This study has 2 arms: Arm A: Cabozantinib alone Patients receive cabozantinib S-malate orally (by mouth or PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B: Cabozantinib + Atezolizumab Patients receive cabozantinib S-malate PO QD on days 1-21 and atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

The purpose of this study is to evaluate the safety and tolerability of casdatifan (a type of targeted therapy) when taken alone in participants with advanced solid tumor malignancies and clear cell renal cell carcinoma (ccRCC) during, and casdatifan in combination with cabozantinib (Cabometyx, a type of targeted therapy) in participants with ccRCC. This study has 2 treatment regimens: Regimen 1: Casdatifan monotherapy Participants will receive casdatifan at various dose levels by mouth (orally, po) once or twice daily. Dosing and dosing schedule will be provided by treatment team. Regimen 2: Casdatifan + Cabozantinib Participants will receive casdatifan orally with cabozantinib. Dosing and dosing schedule will be provided by treatment team.

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.

Kidney cancer is the 12th leading cause of cancer-related death in the United States. Some kidney tumors do not respond well to current treatments. Better treatments are needed. Most patients with advanced clear cell RCC are treated with immunotherapy and targeted therapy. There are few options for patients who have progressed on these therapies. There is currently no widely accepted standard treatment for patients with papillary renal cell carcinoma, although some patients may benefit from targeted therapy. Preclinical data suggest that inhibitors of CDK 4/6 (targeted therapy) might be active in kidney cancer and that these agents might act synergistically with immunotherapy. The objective of this study is to the safety and effectiveness of combining palbociclib (a type of targeted therapy inhibiting CDK4/6) and sasanlimab (a type of immunotherapy). All participants receive treatment with palbociclib given by mouth (PO, orally) + sasanlimab given by subcutaneous injection (sc or sq). Dosage and dosing schedule will be provided by the treatment team.