Kidney Cancer Trials

This phase III trial compares the usual treatment (treatment with ipilimumab and nivolumab followed by nivolumab alone) to treatment with ipilimumab and nivolumab, followed by nivolumab with cabozantinib in patients with untreated renal cell carcinoma that has spread to other parts of the body. The addition of cabozantinib to the usual treatment may make it work better. Immunotherapy, such as nivolumab (Opdivo) and ipilimumab (Yervoy), may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Targeted therapy, such as cabozantinib, 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. It is not yet known how well the combination of cabozantinib and nivolumab after initial treatment with ipilimumab and nivolumab works in treating patients with renal cell cancer that has spread to other parts of the body. This study has 2 arms: Arm A: Nivolumab INDUCTION: Patients receive nivolumab intravenously (IV) in clinic over 30 or 60 minutes PLUS ipilimumab IV over 60 minutes on day 1 of every 21 day cycle, for up to 4 cycles. TREATMENT: Patients receive nivolumab IV over 30 or 60 minutes on day 1 of every 28 day cycle. Arm B: Nivolumab + Cabozantinib INDUCTION: Patients receive nivolumab intravenously (IV) in clinic over 30 or 60 minutes PLUS ipilimumab IV over 60 minutes on day 1 of every 21 day cycle, for up to 4 cycles. TREATMENT: Patients receive nivolumab IV over 30 or 60 minutes on day 1 of every 28 day cycle PLUS cabozantinib orally (by mouth or PO) daily on days 1-28.

This trial tests the target therapy drug INC280 for patients with either hereditary or sporadic papillary renal cell carcinoma. Some patients with papillary renal cell carcinoma are affected by a MET mutation that makes the cancer more aggressive, makes it resistant to chemotherapy, and increases its tendency to spread and become metastatic. INC280 is a MET inhibitor whose effect on the cancer is being evaluated in this study. Participants eligible for this study must have papillary renal cell carcinoma and either bilateral multifocal disease or visible disease that is considered unresectable. Participants will take INC280 as an oral medication twice daily.

Currently, there is no effective treatment for papillary renal cell carcinoma (PRCC) once it has metastasized or spread. PRCC is a particularly aggressive form of kidney cancer that has a lower survival rate, can be resistant to chemotherapy, and has a much higher tendency to metastasize. PRCC can either be hereditary (HLRCC) or sporadic (SPRCC). This combination of targeted therapies using bevacizumab and erlotinib is an attempt to exploit the higher energy requirements of PRCC compared to other forms of kidney cancer. Erlotinib can slow or stop the growth and spread of cancer by blocking a specific protein expressed in cancer cells, and bevacizumab restricts the cancer's access to oxygen and nutrients by preventing it from forming new blood vessels.  During this study, the effectiveness of the treatment will be evaluated for both HLRCC and SPRCC. Treatment will consist of 28-day cycles. IV bevacizumab will be administered every two weeks and oral erlotinib will be administered once daily.

This is a Phase I/II, open-label, multi-center study of axitinib (Inlyta, a type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) in patients with previously treated and untreated advanced renal cell carcinoma (RCC). This clinical study will be composed of a dose finding phase (Phase I) and two parallel dose expansion phases (Phase II). The dose finding phase will assess the safety of the combination and establish a recommended phase II dose in patients with advanced RCC who have received prior systemic therapy for metastatic disease. Phase II will evaluate the effectiveness of the combination in two parallel expansion cohorts in both previously treated and treatment naïve patients. All patients in all phases of this study will receive both drugs, at various doses. Axitinib is taken orally (by mouth) twice daily, although dose and dosing schedule may vary. Nivolumab is given intravenously (IV), dose and dosing schedule may vary.

This is a phase II trial of nivolumab (Opdivo, an immunotherapy) in treatment-naïve patients with clear cell renal cancer. Nivolumab has been shown to have anti-tumor activity in renal cell patients. It is hypothesized that patients may still respond (have anti-tumor activity) by giving ipilimumab with nivolumab when the patient is no longer responding to nivolumab alone.

In Part A, nivolumab 240 mg will be given intravenously (IV) in clinic once every two weeks for six doses. Patients who remain on study after re-evaluation will receive nivolumab 360 mg IV in clinic once every three weeks.

In Part B, nivolumab 3 mg/kg AND ipilimumab (Yervoy, an immunotherapy) will both be given IV in clinic once every three weeks for four doses. Patients who remain on study after re-evaluation will receive nivolumab 360 mg IV in clinic once every three weeks.

In this four part study, NKTR-214 (a type of immunotherapy) will be administered in combination with nivolumab (Opdivo, a type of immunotherapy) in Parts 1 & 2, and with nivolumab and ipilimumab (Yervoy, a type of immunotherapy) in Parts 3 & 4. In Part 1, the safety, effectiveness and recommended dose of NKTR-214 in combination with nivolumab will be determined. In Part 2, the clinical benefit, safety, and tolerability of combining NKTR-214 with nivolumab Renal Cell Carcinoma and Urothelial Carcinoma. In Part 3, the safety, effectiveness and dose level of NKTR-214 in combination with nivolumab and ipilimumab will be determined. In Part 4, the clinical benefit, safety, and tolerability of the combination of all three drugs will be evaluated in select patients with renal cell carcinoma. All three drugs target the immune system and may act together to promote anti-cancer effects. This study has 2 arms: All drugs are given intravenously (IV) in clinic. Arm A: Combination of NKTR-214 + nivolumab Part 1: Patients with select tumor types will receive NKTR-214 doses administered either once every 2 weeks or once every 2 weeks, in combination with 360 mg of nivolumab once every 3 weeks or 240 mg nivolumab once every 2 weeks. Part 2: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 and nivolumab (as determined by Part 1 of the trial). Arm B: Combination of NKTR-214 + nivolumab + ipilimumab Part 3: The first schedule to be evaluated, Cohort A, is NKTR-214 0.006 mg/kg and nivolumab 360 mg once every 3 weeks with the addition of ipilimumab 1 mg/kg (kilogram, based on your weight) once every 6 weeks. Upon review of safety, tolerability, and other data collected in Cohort A, alternative doses/schedules may be considered where ipilimumab will be administered at a later cycle. Part 4: Additional patient cohorts with select tumor types will be dosed at the dose/schedule of NKTR-214 in combination with nivolumab and ipilimumab (as determined by Part 3 of the trial).

The purpose of this study is to determine whether nivolumab (Opdivo, an immunotherapy) in combination with other therapies is more effective than nivolumab in combination with ipilimumab (Yervoy, an immunotherapy) in treating patients with advanced renal cell carcinoma. It is hypothesized that patients will have an increased clinical response (decrease in tumor size) when given a combination of nivolumab and BMS-986016 (an immunotherapy) than when given a combination of nivolumab and ipilumumab.

Nivolumab, ipilimumab, and the experimental drug BMS-986016 are all given intravenously (IV) in clinic. The dosing schedule will be either:

1. Nivolumab is given intravenously IV at 3mg/kg PLUS ipilimumab given IV at 1mg/kg once every 3weeks for 4 doses. Six weeks after the last dose of combination study, nivolumab will be given IV at 480 mg one every 4 weeks for 3 doses OR

2. Nivolumab is given IV at 240 mg PLUS BMS-986016 is given IV at 80 mg once every 2 weeks for 12 doses.

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 is a multicenter, randomized, double-blinded, controlled Phase 3 trial of cabozantinib (Cabometyx, a type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) versus nivolumab and ipilimumab in combination with matched placebo. The primary objective of this study is to evaluate the effect of cabozantinib in combination with nivolumab and ipilimumab ("triplet") on the duration of progression-free survival (PFS) versus nivolumab and ipilimumab. A secondary objective is to evaluate the effect of triplet combination on the duration of overall survival (OS).

Metastatic renal cell carcinoma (RCC) is an incurable condition. Current therapy for this disease consists of targeted therapies and immunotherapies. Long-term survival can be achieved however, of those patients treated with immunotherapy, three quarters will not respond at all and only 5-8% will achieve a complete and long term response. Gene transfer is a new cancer therapy that takes white blood cells from a person and grows them in a lab. The cells are changed with a virus to attack tumor cells, then returned to the person. Researchers want to see if this therapy fights kidney cancer cells. Our team isolated a tumor-specific cytotoxic T lymphocyte (CTL, a type of white blood cell that kills cancer cells) line from peripheral blood obtained after an allogeneic transplant from a patient who showed prolonged tumor regression. We identified a HERV-E derived antigen expressed in the patient s ccRCC cells to be the target of this T-cell clone. Remarkably, we found this HERV-E was expressed in the majority of ccRCC cells with no expression in normal tissues. This research protocol is designed to evaluate the safety and effectiveness of the infusion of HERV-E T cells. Treatment: • Participants will have leukapheresis. Blood will be removed by a needle in an arm. It will go through a machine that removes white blood cells. Plasma and red cells will be returned through a needle in the participant’s other arm. • Participants cells will be grown in the lab and genetically changed. • Participants will stay in the hospital 2-3 weeks. In the hospital participants will: • Get 2 chemotherapy drugs by catheter (thin plastic tube) inserted into a vein in the chest. • Get the changed cells via catheter. • Get a drug to increase white blood cell count and one to make the cells active. • Recover for about a week. • Have lab and blood tests. After leaving the hospital, participants will: • Take an antibiotic for several months. • Have leukapheresis. • Have one- or two-day clinic visits every few weeks for 2 years, and then as determined by their doctor. These will include blood and lab tests, imaging studies, and physical exam. • Participants will have follow-up checks for up to 15 years.

This randomized phase II trial studies how well cabozantinib-s-malate (Cabometyx, a type of targeted therapy), crizotinib (Xalkori, a type of targeted therapy), volitinib (Savolitinib, a type of targeted therapy), or sunitinib malate (Sutent, a type of targeted therapy) work in treating patients with kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body (metastatic disease). Cabozantinib-s-malate, crizotinib, volitinib, and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Patient will be randomized to one of four arms:

Arm I: Sunitinib

Patients receive sunitinib malate taken orally (at home) once daily on days 1-28, followed by a rest period (where you do not take the study drug) days 29-42. Courses repeat every 42 days.

Arm II: Cabozantinib

Patients receive cabozantinib-s-malate taken orally (at home) once daily on days 1-42. Courses repeat every 42 days.

Arm III: Crizotinib

Patients receive crizotinib taken orally (at home) twice daily on days 1-42. Courses repeat every 42 days.

Arm IV: Volitinib

Patients receive volitinib taken orally (at home) once daily on days 1-42. Courses repeat every 42 days.

The main purpose of this study is to compare the overall response rate (ORR) and overall survival (OS) of NKTR-214 (a type of immunotherapy) combined with nivolumab (a type of immunotherapy) to that of a tyrosine kinase inhibitor (TKI, a type of targeted therapy) monotherapy in intermediate and poor-risk participants with previously untreated advanced renal cell carcinoma (RCC). This study has 2 arms: specific doses and dosing schedules to be provider by the participating site. Arm 1: Combination of NKTR-214 + Nivolumab Participants will receive NKTR-214 in combination with Nivolumab given intravenously (IV). Arm 2: Sunitinib (Sutent) or Cabozantinib (Cabometyx) Participants will receive the treating physician’s choice of either one of these two treatment options. Both drugs are taken by mouth.

This is a Phase II, open-label, safety, pharmacodynamic (how the drugs work in the body) and effectiveness study of entinostat (at type of targeted therapy) in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) in subjects with metastatic renal cell carcinoma (RCC) who have progressed on ipilimumab + nivolumab regimen. It is thought that adding entinostat to the ipilimumab + nivolumab regimen will help the regimen work better or help it start working again. This study has 1 arm: Entinostat, Nivolumab and Ipilimumab: Entinostat is given at 5mg, 3mg, or 2mg orally (by mouth) on days 1, 8, 15 of each cycle, plus Nivolumab 3 mg/kg IV (intravenously) on day1 and Ipilimumab 1 mg/kg IV on day 1. Each cycle is 21 days.

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 randomized phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with or without nivolumab (Opdivo, a type of immunotherapy) in treating patients with kidney cancer that is limited to a certain part of the body (localized). Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving nivolumab before nephrectomy may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. After nephrectomy, it may increase survival. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

Patients will be randomized to one of two arms:

Arm A Nivolumab + nephrectomy – Patients receive nivolumab intravenously (IV) over 60 minutes every 14 days for 2 cycles. Each cycle is 28 days. Patients then undergo partial or radical nephrectomy. After surgery, patients then receive nivolumab IV every 14 days for 6 cycles, and then once every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Arm B – Patients undergo partial or radical nephrectomy followed by observation.

After completion of study treatment, all patients are followed up every 3 months for 2 years, every 6 months for 3 years, and every 12 months for 5 years.

The primary objective of this study is to compare MK-6482 (a type of targeted therapy) to everolimus (Afinitor, a type of targeted therapy) with respect to progression-free survival (PFS, the time it takes your cancer to get larger) and to compare everolimus with respect to overall survival (OS, how long you live overall, whether your cancer grows or not). The belief is that MK-6482 will work better than everolimus with respect to PFS and OS. Treatment – this study has 2 arms Arm A: MK-6482 Participants receive 120 mg of MK-6482 orally (by mouth or PO) once daily. Arm B: Everolimus Participants receive 10 mg of Everolimus orally (by mouth or PO) once daily.