Kidney Cancer Trials

This is a phase I/Ib, open-label, safety, and pharmacodynamics (how the drug works in the body) study of pembrolizumab (an immunotherapy) in combination with vorinostat (a targeted therapy) in patients with advanced renal or urothelial cell carcinoma. It is hypothesized that giving these drugs together will increase clinical response (decrease in tumor size) more than either drug given alone.

This clinical study will consist of a Dose Finding Phase and an Expansion Phase. The Dose Finding Phase will estimate the Recommended Phase II Dose in patients with advanced renal and urothelial cell carcinoma patients. The Dose Finding Phase will lead to the identification of an Expansion Test Dose (the highest tested dose that is declared safe and tolerable by the investigators and sponsor) for pembrolizumab in combination with vorinostat.

Patients will be treated with oral vorinostat every day for 14 days (taken at home) and with pembrolizumab at the fixed dose of 200 mg IV (given in the clinic) once every 21 days. Each cycle is 21 days. Two dose levels of vorinostat will be tested, 100 mg and 200 mg.

This study evaluates the safety and efficacy of treatment with nivolumab prior to a nephrectomy in patients with high-risk clear-cell renal cell carcinoma. Nivolumab is a drug that is part of a class of immunotherapy agents called monoclonal antibodies that have recently been approved as treatment for several other cancers. It prevents the expression of a specific protein associated with tumor cells that stops the immune system from attacking the cancer. Blocking this protein frees the T-cells (a type of immune cell) so that they can trigger an immune response that kills tumor cells and halts the growth of the cancer. Participants will receive a nivolumab injection every two weeks for a total of three injections prior to their nephrectomy.

This trial focuses on enhancing diagnostic tools for kidney cancer. The radioactive tracer 18F-DCFPyL is being studied for use during PET scans. A radiotracer is a radioactive agent that allows for identification of a certain structure, in this case the tumor. 18F-DCFPyL is attracted to a protein found on the surface of cancer cells. It is this attraction that allows the PET scan to identify the cancer. In previous studies, it was indicated that cancer cells may be more attracted to the 18F-DCFPyL, giving doctors a more accurate image of the cancer. Eligible patients are those who have had cancer staging done using either a CT scan or an MRI within the past 90 days. Participants in this study will undergo a PET/CT scan.

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.

Everolimus is a targeted therapy called an mTOR inhibitor that stops tumor growth by preventing cancer cells from multiplying and decreasing blood supply to cancer cells. It is already approved to treat advanced renal cell carcinoma after other treatments have failed. This trial tests the efficacy of everolimus for patients with either BHD-associated renal cancer or advanced sporadic chromophobe renal cancer, for which there is no approved drug treatment. Both BHD-associated and sporadic chromophobe renal cancer appear to have many similar molecular features, and previous studies have indicated that they might respond to an mTOR inhibitor such as everolimus. This trial is designed to test the tumor response of each of these cancers to everolimus. Participants will be given Everolimus to be taken orally for up to a year.

There is currently no approved treatment for advanced forms of hereditary leiomyomatosis and renal cell cancer (HLRCC), succinate dehydrogenase renal cell carcinoma (SDH-RCC), or sporadic papillary renal cell carcinoma. This trials aims to determine whether a combination of vandetanib plus metformin is a potential treatment for persons with advanced forms of these three cancers. Metformin is most commonly prescribed for type 2 diabetics, but in a recent study it was shown to improve progression-free and overall survival in cancer patients when given in combination with surgery. Vandetanib is a targeted therapy, currently used to treat thyroid cancer, that stops cancer cell growth and slows its spread to the rest of the body. This study will be conducted in two stages. Stage one is to determine the safe dose of the combination treatment. In stage two, participants will be given both vandetanib and metformin as oral medications to be taken daily for up to a year. Participants in stage two will be evaluated based upon which of the three types of cancer they have.

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.

The purpose of this study to determine the safety and effectiveness of radiation therapy in combination with nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) in patients with metastatic renal cell carcinoma.

Patients will receive both nivolumab (given intravenously, or IV in clinic) and ipilimumab (given IV in clinic) plus radiation therapy to one or two metastatic cancer sites, followed by nivolumab given alone.

Cancer treatments that couple pharmacological (drug) activation of tumor antigen presentation with activation and expansion of CD8+ T and natural killer (NK) cells in the tumor environment have the potential to induce an effective anti-tumor immune response in patients. NKTR-262 is a type of immunotherapy. In preclinical studies, a single intratumoral (directly into the tumor) injection of NKTR-262 plus intravenous (IV) NKTR-214 (a type of immunotherapy) resulted in shrinkage of cancer, including outside of the original tumor that was injected. Preliminary clinical data show NKTR-214 plus nivolumab (a type of immunotherapy) enhances immune-stimulatory responses. This trial will assess safety and anti-tumor activity of NKTR-262 with NKTR-214 +/- nivolumab for the treatment of selected cancers, including kidney cancer and urothelial cancer. This study has 2 arms: All doses of study medication will be given in clinic. Arm A: NKTR-262 + NKTR-214 Phase 1 Doublet: NKTR-262 in escalating doses, will be combined with NKTR-214. The goal of this dose escalation part of the study is to establish a safe and tolerable recommended phase 2 dose (RP2D) for NKTR-262 in combination with NKTR-214 in a once every 3 week fixed dose. Phase 2 Doublet: NKTR-262 RP2D will be combined with a once every 3 week dose of NKTR-214 in select tumor indications (including kidney cancer and urothelial cancer) to evaluate anti-tumor activity and to obtain additional safety data. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects. Arm B: Triplet: NKTR-262 + NKTR-214 + Nivolumab Phase 1 Triplet: The RP2D of NKTR-262 RP2D will be combined with a once every 3 week dose regimen of NKTR-214 plus nivolumab. The goal of this arm is to establish the safety and tolerability of the triplet. Phase 2 Triplet: The RP2D of NKTR-262 will be combined with a once every 3 week dose regimen of NKTR-214 plus nivolumab in select tumor indications to evaluate anti-tumor activity and to obtain additional safety data. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.

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.

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (Keytruda, an immunotherapy) in combination with axitinib (Inlyta, a targeted therapy) versus sunitinib (Sutent, a targeted therapy) alone as a first-line treatment for participants with advanced/metastatic renal cell carcinoma. The primary hypotheses of this study are that the combination therapy of pembrolizumab plus axitinib is superior to sunitinib alone with respect to progression-free survival and overall survival.

Patients will receive either:

1. Pembrolizumab and Axitinib Combination Therapy – participants will receive pembrolizumab 200 mg intravenously (IV) in clinic once every 3 weeks PLUS axitinib 5 mg taken orally (at home) twice daily OR

2. Sunitinib Monotherapy – participants will receive sunitinib 50 mg taken orally (at home) once daily for 4 weeks followed by a 2 week break.

This is a Phase III, multicenter, randomized, placebo-controlled, double-blind study to evaluate the efficacy (how well it works) and safety of atezolizumab (a type of immunotherapy) versus placebo in participants with Renal Cell Carcinoma who are at high risk of disease recurrence following nephrectomy.

Patients will be randomized to one of two arms:

Arm A: Atezolizumab

Participants will be given atezolizumab 1200 milligrams (mg) by intravenous (IV) infusion every once 3 weeks (in clinic) for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).

Arm B: Placebo

Participants will receive a placebo (that matches atezolizumab) by intravenous (IV) infusion every once 3 weeks (in clinic) for 16 cycles (each cycle=21 days) or 1 year (whichever occurs first).

The purpose of this study is to evaluate the safety and effectiveness of pembrolizumab (Keytruda or MK-3475, a type of immunotherapy) in the treatment of adult participants who have undergone nephrectomy (surgical removal of the kidney) and have intermediate-high risk, high risk, or no evidence of disease renal cell carcinoma (RCC) with a clear cell component.

The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS, how long it takes the cancer to be seen on CT scans).

Patients are randomized to one of two arms:

Arm A: Pembrolizumab

Participants receive pembrolizumab 200 mg intravenous (IV, in clinic) infusion on Day 1 of each 3-week cycle for up to 17 cycles.

Arm B: Placebo

Participants receive placebo (saline solution) IV infusion (in clinic) on Day 1 of each 3-week cycle for up to 17 cycles.

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.

This study investigates the safety of nivolumab (Opdivo, an immunotherapy) in combination with ipilimumab (Yervoy, an immunotherapy) in patients with previously untreated advanced or metastatic renal cell cancer. It is hypothesized that giving these drugs together will increase patients’ clinical response (decrease in tumor size) more than either drug given alone.

Both drugs are given intravenously (IV) in clinic. Each cycle is eight weeks.

Cohort 1: Nivolumab is given IV at 6mg/kg combined with ipilimumab given IV at 1mg/kg once every eight weeks. Nivolumab will also be given IV at 480mg once every eight weeks, staggered between the combination doses.

Cohort 2: Nivolumab is given IV at 3mg/kg combined with ipilimumab given IV at 1mg/kg once every three weeks for four doses, then maintenance nivolumab is given IV at 480mg once every four weeks.

Cohort 3: Nivolumab is given IV at 3mg/kg combined with ipilimumab given IV at 1mg/kg once every three weeks for four doses, then maintenance nivolumab is given IV at 480mg once every four weeks.

Cohort 4: Nivolumab is given at 3mg/kg combined with ipilimumab given at 1mg/kg once every three weeks for four doses, then maintenance nivolumab given IV at 480mg once every four weeks.

This study compares CB-839 (a type of targeted therapy) in combination with everolimus (Affinitor, a type of targeted therapy) versus placebo with everolimus in patients with advanced or metastatic renal cell carcinoma (RCC). This is a Phase II, randomized, double blind, placebo controlled study. The study has 2 arms: each cycle is 28 days Arm A: CB-839 plus everolimus CB-839 tablets are taken by mouth (orally) twice daily in combination with everolimus standard of care, taken by mouth daily everolimus for each 28 day cycle. Arm B: Placebo tablets are taken by mouth twice daily in combination with everolimus standard of care, taken by mouth daily everolimus for each 28 day cycle.

This randomized phase II trial studies how well cabozantinib-s-malate (Cabometyx, a type of targeted therapy) works compared to sunitinib malate (Sutent, a type of targeted therapy) in treating patients with previously untreated kidney cancer that has spread from where it started to nearby tissue or lymph nodes or to other places in the body (metastatic). Cabozantinib-s-malate and sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cabozantinib-s-malate is more effective than sunitinib malate in treating patients with kidney cancer.

Patients will be randomized to one of two arms:

Arm 1 Cabozantinib

Patients take cabozantinib-s-malate by mouth once daily for 6 weeks. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Arm 2 Sunitinib

Patients take sunitinib malate by mouth once daily for 4 weeks, followed by a 2 week rest period. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

The purpose of this study is to determine whether the combination of nivolumab (Opdivo, a type of immunotherapy) and ipilimumab (Yervoy, a type of immunotherapy) is safe and effective for delaying or preventing recurrence of cancer in patients who have experienced the partial or entire removal of a kidney.

Patients will be randomized to one of two arms:

Arm A Nivolumab + Ipilimumab

Nivolumab is given intravenously (IV, in clinic) at 240 mg once every 2 weeks for 12 doses total. Ipilimumab is given IV (in clinic) at 1mg/kg once every 2 weeks starting at Week 6.

Arm B Placebo

The placebo (a benign fluid with no therapeutic effect) will be given IV (in clinic) on the same schedule as the treatment arm (Arm A).

Many tumor cells, in contrast to normal cells, have been shown to require the amino acid glutamine to produce energy for growth and survival. To exploit the dependence of tumors on glutamine, CB-839 (a type of targeted therapy), a potent and selective inhibitor of the first enzyme in glutamine utilization, glutaminase, will be tested in this Phase 1 study in patients with solid tumors.

CB-839 oral capsules are taken two or three times daily in 21-day cycles (at home).

Patients with advanced clear cell renal cell carcinoma (RCC) or papillary RCC will be treated with everolimus (Affinitor, a type of targeted therapy) in combination with CB-839.

CB-839 oral capsules are taken twice daily (at home) in combination with standard dose everolimus (10 mg taken once daily at home) in 28-day.

Patients with a diagnosis of locally-advanced, inoperable or metastatic RCC will be treated with cabozantinib (Cabometyx, a type of targeted therapy) in combination with CB-839.

CB-839 oral capsules are taken twice daily (at home) in combination with standard dose cabozantinib (60 mg taken once daily at home) in 28-day cycles.

All patients will be assessed for safety, pharmacokinetics (concentration of the drug in the blood), pharmacodynamics (inhibition of glutaminase), biomarkers (biochemical markers that may predict responsiveness in later studies), and tumor response.

This is an open-label, multi-center, randomized, Phase 1b clinical study to assess the safety, tolerability, and preliminary therapeutic activity of RO6874281 (a type of immunotherapy) in combination with atezolizumab (Tecentriq, a type of immunotherapy) with/without bevacizumab (Avastin, a type of targeted therapy) in participants with unresectable advanced and/or metastatic renal cell carcinoma (RCC). The study will consist of a dose-escalation part and an extension part. The dose-escalation phase of this study has 2 arms: Arm A: Atezolizumab + RO6874281 Atezolizumab will be administered at a dose of 840 milligrams (mg) as an intravenous (IV) infusion on Days 1, 15, 29, then once every 2 weeks from Day 29 onwards. It will be administered prior to RO6874281 administration. RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, then once every 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Arm B: Atezolizumab + RO6874281 + Bevacizumab Dosing of Atezolizumab and RO6874281 is the same as in Arm A. Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) as an IV infusion on Days 15, 29, then once every 2 weeks from Day 29 onwards. It will be administered after the atezolizumab administration, and prior to RO6874281 administration. The extension phase of this study has 4 arms: dose of RO6874281 will be based on findings in the dose-escalation phase. Arm A: Atezolizumab + RO6874281 Atezolizumab will be administered at a dose of 840 milligrams (mg) as an intravenous (IV) infusion on Days 1, 15, 29, then once every 2 weeks from Day 29 onwards. It will be administered prior to RO6874281 administration. RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, then once every 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be at a dose determined in the escalation phase. Arm B: Atezolizumab + RO6874281 + Bevacizumab Dosing of Atezolizumab and RO6874281 is the same as in Arm A. Bevacizumab will be administered at a dose of 10 milligrams per kilogram (mg/kg) as an IV infusion on Days 15, 29, then once every 2 weeks from Day 29 onwards. It will be administered after the atezolizumab administration, and prior to RO6874281 administration. Arm C: Atezolizumab + RO6874281 Atezolizumab will be administered at a dose of 1200mg as an IV infusion once every 3 weeks. RO6874281 will be administered as an IV infusion once every 3 weeks at the dose determined in the dose-escalation phase. Arm D: Atezolizumab + RO6874281 + Bevacizumab Dosing of Atezolizumab and RO6874281 is the same as in Arm C. Bevacizumab will be administered at a dose of 15mg/kg as an IV infusion once every 3 weeks.

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.

This study is a randomized Phase 2 evaluation of CB-839 (a type of targeted therapy) in combination with cabozantinib (Cabometyx, a type of targeted therapy) versus placebo with cabozantinib in Renal Cell Carcinoma patients with at least one and not more than 2 prior therapies in the advanced or metastatic setting. The study has 2 arms: Arm A: CB-839 + Cabozantinib CB-839 taken orally twice daily + cabozantinib taken orally once daily. Arm B: Placebo + Cabozantinib Placebo taken orally twice daily + cabozantinib taken orally once daily.