Genetic-Guided Therapy for Kidney Cancer
Recruiting in Palo Alto (17 mi)
+5 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vanderbilt-Ingram Cancer Center
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Hypertension, Active infection, Cardiovascular, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial tests whether using genetic testing of tumor tissue to select the optimal treatment regimen works in treating patients with clear cell renal cell (kidney) cancer that has spread to other places in the body (advanced or metastatic). The current Food and Drug Administration (FDA)-approved regimens for advanced kidney cancer fall into two categories. One treatment combination includes two immunotherapy drugs (nivolumab plus ipilimumab), which are delivered by separate intravenous infusions into a vein. The other combination is one immunotherapy drug (nivolumab infusion) plus an oral pill taken by mouth (cabozantinib). Nivolumab and ipilimumab are "immunotherapies" which release the brakes of the immune system, thus allowing the patient's own immune system to better kill cancer cells. Cabozantinib is a "targeted therapy" specifically designed to block certain biological mechanisms needed for growth of cancer cells. In kidney cancer, cabozantinib blocks a tumor's blood supply. The genetic (DNA) makeup of the tumor may affect how well it responds to therapy. Testing the makeup (genes) of the tumor, may help match a treatment (from one of the above two treatment options) to the specific cancer and increase the chance that the disease will respond to treatment. The purpose of this study is to learn if genetic testing of tumor tissue may help doctors select the optimal treatment regimen to which advanced kidney cancer is more likely to respond.
Do I have to stop taking my current medications for the trial?
The trial does not specify if you need to stop taking your current medications. However, it allows the use of anti-hypertensive medications and certain corticosteroids, so you may be able to continue some treatments. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug combination of cabozantinib, nivolumab, and ipilimumab for kidney cancer?
Research shows that cabozantinib combined with nivolumab improved survival rates in advanced kidney cancer compared to another drug, sunitinib. Additionally, cabozantinib has been recognized as a breakthrough drug for advanced kidney cancer due to its effectiveness in previous trials.
12345Is the genetic-guided therapy for kidney cancer safe?
Cabozantinib, Nivolumab, and Ipilimumab have been studied for safety in treating advanced kidney cancer. Some studies have reported adverse events (side effects) when these drugs are used alone or in combination, but they are generally considered safe for use in humans with careful monitoring.
25678What makes the drug combination of Cabozantinib, Ipilimumab, and Nivolumab unique for kidney cancer?
This drug combination is unique because it combines Cabozantinib, which targets multiple pathways involved in cancer growth, with Ipilimumab and Nivolumab, which are immune checkpoint inhibitors that help the immune system attack cancer cells. This approach is novel as it targets both the cancer cells directly and boosts the body's immune response against them.
257910Eligibility Criteria
Adults with advanced or metastatic clear cell renal cell carcinoma, who haven't had systemic therapy for RCC and have a Karnofsky performance status of >=70%. Participants need measurable lesions per RECIST 1.1, adequate organ function, and must consent to genetic testing of their tumor tissue. Women must not be pregnant and agree to contraception.Inclusion Criteria
I am 18 years old or older.
I am a woman who can still have children and have not had surgery to remove my reproductive organs.
I am a woman over 45 and have not had a period for 12 months due to menopause.
+11 more
Exclusion Criteria
I am currently receiving treatment through an IV for an infection.
I have not had major surgery within the last 14 days.
I use low-dose steroids or hormone replacement without having an active autoimmune disease.
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction
Patients receive ipilimumab and nivolumab intravenously on day 1. Cycles repeat every 21 days for 4 cycles.
12 weeks
4 visits (in-person)
Maintenance
Patients receive nivolumab intravenously on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Variable, up to 4 years
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
1 visit (in-person)
Participant Groups
The trial is testing if genetic testing can help choose better treatment for kidney cancer that has spread. It compares two FDA-approved treatments: one combines two immunotherapies (nivolumab plus ipilimumab) via IV infusions; the other pairs nivolumab infusion with an oral pill (cabozantinib).
2Treatment groups
Experimental Treatment
Group I: Arm II (nivolumab, cabozantinib)Experimental Treatment2 Interventions
Patients receive nivolumab IV on day 1 and cabozantinib PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Group II: Arm I (ipilimumab, nivolumab)Experimental Treatment2 Interventions
INDUCTION: Patients receive ipilimumab and nivolumab IV on day 1. Cycles repeat every 21 days for 4 cycles.
MAINTENANCE: Patients receive nivolumab IV on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇺🇸 Approved in United States as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇨🇦 Approved in Canada as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
🇯🇵 Approved in Japan as Cabometyx for:
- Renal cell carcinoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Chao Family Comprehensive Cancer CenterOrange, CA
University Hospitals Seidman Cancer CenterCleveland, OH
City of Hope National Medical CenterDuarte, CA
Cleveland ClinicCleveland, OH
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Vanderbilt-Ingram Cancer CenterLead Sponsor
United States Department of DefenseCollaborator
National Cancer Institute (NCI)Collaborator
References
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC).
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]The efficacy and safety of treatment with cabozantinib in combination with nivolumab and ipilimumab in patients with previously untreated advanced renal-cell carcinoma are unknown.
Neoadjuvant nivolumab and cabozantinib in advanced renal cell carcinoma in a horseshoe kidney - how to achieve a safe and radical resection? a case report and review of the literature. [2023]Neoadjuvant nivolumab and cabozantinib in locally advanced renal cell carcinoma in a horseshoe kidney is a novel therapeutic approach in the preoperative setting.
Cost-Effectiveness Analysis of First-Line Nivolumab Plus Cabozantinib for Advanced Renal Cell Carcinoma in the United States. [2021]Nivolumab plus cabozantinib improved progression-free survival and overall survival compared with sunitinib in the first-line treatment of advanced renal cell carcinoma (RCC) according to CheckMate 9ER study.
Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection. [2022]Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib's designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC.
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]Recently, many agents and combinations for metastatic and advanced renal cell carcinoma have been approved. This study aims to highlight the comprehensive differences in adverse events (AEs) between cabozantinib (CAB) plus nivolumab (NIVO) and ipilimumab (IPI) plus NIVO based on a real-world big dataset.
CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma. [2022]Cabozantinib is an inhibitor of multiple tyrosine kinases, including AXL, MET and VEGF receptors. Here, we describe the rationale and design for the phase II CaboPoint trial (ClinicalTrials.gov identifier: NCT03945773), which will evaluate the efficacy and safety of cabozantinib as a second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma whose disease has progressed despite checkpoint inhibitor therapy. Patients will be recruited into two cohorts: prior ipilimumab plus nivolumab (cohort A) or prior checkpoint inhibitor-VEGF-targeted therapy (cohort B). All patients will receive once-daily oral cabozantinib 60 mg for up to 18 months. The primary end point is objective response rate. Secondary end points include overall survival, progression-free survival and safety.
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.
Updated EAU Guidelines for Clear Cell Renal Cancer Patients Who Fail VEGF Targeted Therapy. [2018]The European Association of Urology renal cancer guidelines have been updated to recommend nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of VEGF targeted therapy.
European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor-Targeted Therapy. [2018]The European Association of Urology renal cancer guidelines panel recommends nivolumab and cabozantinib over the previous standard of care in patients who have failed one or more lines of vascular endothelial growth factor-targeted therapy. New data have recently become available showing a survival benefit for cabozantinib.