Cabozantinib + Nivolumab + Radiation for Metastatic Kidney Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Must not be taking: Anticoagulants, Steroids, Kinase inhibitors, others
Disqualifiers: Cardiovascular disease, Autoimmune disease, Infection, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to find out whether the combination of cabozantinib, nivolumab, and radiation therapy is a safe and effective treatment that causes few or mild side effects in people with renal cell cancer that has spread to the brain. The researches will also look at how the study treatment affects the quality of life of participants. They will measure the quality of life by having participants complete questionnaires.
Do I need to stop my current medications to join the trial?
The trial requires a 2-week period without taking any small molecule kinase inhibitors or VEGF-targeted therapies before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug combination of Cabozantinib and Nivolumab for metastatic kidney cancer?
The combination of Cabozantinib and Nivolumab has been shown to improve progression-free survival and overall survival compared to another drug, Sunitinib, in the treatment of advanced kidney cancer, according to the CheckMate 9ER study. This combination is also approved as a first-line treatment for advanced kidney cancer in several countries, indicating its effectiveness.
12345Is the combination of Cabozantinib and Nivolumab safe for humans?
The combination of Cabozantinib and Nivolumab has been studied for safety in treating advanced kidney cancer. While the treatment can have side effects like diarrhea, fatigue, and skin reactions, these are generally manageable with proper care and dose adjustments.
23678What makes the drug combination of Cabozantinib and Nivolumab unique for treating metastatic kidney cancer?
The combination of Cabozantinib and Nivolumab is unique because it pairs a multi-targeted tyrosine kinase inhibitor (Cabozantinib) with an immune checkpoint inhibitor (Nivolumab), which has shown to improve progression-free survival and overall survival compared to standard treatments like sunitinib for advanced renal cell carcinoma. This combination is also associated with better health-related quality of life for patients.
12369Eligibility Criteria
This trial is for adults with renal cell carcinoma that has spread to the brain. Participants must be over 18, have a good performance status (able to carry out daily activities), and agree to use effective contraception if necessary. They should not have had certain treatments recently, like whole brain radiotherapy or experimental drugs within the last month, and should not need major surgery during the study.Inclusion Criteria
My blood and organ tests meet the required health standards.
I am 18 years old or older.
I have recovered from any serious side effects of my previous treatments.
+5 more
Exclusion Criteria
Previously identified allergy or hypersensitivity to components of the treatment
I am on steroids or immunosuppressants for an autoimmune disease, with some exceptions.
I have not had significant blood vessel problems in the last 6 months.
+25 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive cabozantinib and nivolumab with radiation therapy. Cabozantinib is administered at 40 mg PO daily and nivolumab at 480 mg IV every 4 weeks. Radiation is delivered as stereotactic radiosurgery over 1-5 fractions.
8 weeks
Safety Monitoring
Participants are monitored for safety, specifically for CNS toxicity, over a 56-day period.
8 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment, including quality of life assessments through questionnaires.
1 year
Participant Groups
The study tests a combination of cabozantinib and nivolumab with stereotactic radiosurgery on patients with kidney cancer in the brain. It aims to assess safety, effectiveness, and impact on quality of life through questionnaires.
1Treatment groups
Experimental Treatment
Group I: Cabozantinib and Nivolumab With Radiation TherapyExperimental Treatment3 Interventions
Patients being newly initiated on cabo/nivo will be started on with cabozantinib 40 mg PO daily and nivolumab 480 mg IV day Q4 weeks
o Dose de-escalation of cabozantinib for toxicity will be allowed per prespecified toxicity dose levels
Radiation will be stereotactic radiosurgery, delivered over 1-5 fractions with a total dose of 18-30Gy depending on fractionation schedule per the discretion of the treating radiation oncologist. Standard institutional regimens such as 18-24 Gy in a single fraction, 24-27 Gy in three fractions, and 25-30 Gy in five fractions are permissible.
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:
Memorial Sloan Kettering Monmouth (All Protocol Activities)Middletown, NJ
Memorial Sloan Kettering Bergen (All Protocol Activities)Montvale, NJ
Memorial Sloan Kettering Cancer Suffolk - Commack (All Protocol Activities)Commack, NY
Memorial Sloan Kettering Nassau (All Protocol Activities)Uniondale, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
ExelixisIndustry Sponsor
References
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]Dual therapy with a tyrosine kinase inhibitor (TKI) and either a programmed death protein/ligand 1 (PD-1/PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor has proven efficacy as treatment for previously-untreated advanced renal cell carcinoma (RCC). The combination of the multi-targeted TKI cabozantinib (Cabometyx®) and the anti-PD-1 monoclonal antibody nivolumab (Opdivo®) is approved as first line treatment for RCC in the EU, USA and multiple other countries. In the CheckMate 9ER trial, combination therapy with cabozantinib and nivolumab was superior to sunitinib monotherapy as first line treatment for advanced RCC, demonstrating significantly longer progression-free survival and, importantly, improved overall survival. Patients receiving the combination were also more likely to respond than those treated with sunitinib monotherapy. In addition, health-related quality of life was significantly better with cabozantinib plus nivolumab at nearly all time points during the study. The tolerability profile of the combination was consistent with that seen in previous studies evaluating the two drugs as monotherapy, although more patients who received the combination had serious adverse events than those treated with sunitinib monotherapy. In summary, cabozantinib plus nivolumab is a recommended option for first-line treatment of previously-untreated advanced 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.
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.
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.
Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib. [2023]The effectiveness of nivolumab plus cabozantinib for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus remains unclear.
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).
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.
Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.
[Pharmacological properties and clinical outcomes of the anti-cancer drug, cabozantinib (CABOMETYX®)]. [2022]Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, and AXL, among others. This drug is considered to exert excellent antitumor effects by inhibiting these targets simultaneously. Significant improvement in the primary endpoint (overall survival or PFS) were observed in patients on CAB in comparison with controls in a phase-III study in patients with renal cell carcinoma, progressed after treatment with anti-angiogenic agents, and in another phase-III study in patients with previously treated, advanced hepatocellular carcinoma. These results led to the approval of CAB in Japan in 2020 as a therapeutic agent for unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma progressed after cancer chemotherapy, under the trade name of CABOMETYX® (20 mg, and 60 mg tablets). It has been suggested that CAB may modulate the immune system in favor of antitumor immunity and combined use with PD-1 checkpoint inhibitors may exert a synergistic effect. In a phase-III study that examined the efficacy of combination therapy with CAB and nivolumab in treatment-naive patients with advanced renal cell carcinoma, progression-free survival was significantly increased in patients on combination therapy over patients on sunitinib monotherapy. Three global phase-III clinical studies of combination therapy with atezolizumab and CAB in patients with non-small cell lung cancer, castration-resistant prostate cancer, and renal cell carcinoma, are in progress to confirm the efficacy of CAB.