Sequential Therapy for Kidney Cancer
Palo Alto (17 mi)Overseen byChe-Kai Tsao
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Icahn School of Medicine at Mount Sinai
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a pilot, single-center, single-arm study where 20 patients with metastatic or unresectable clear cell renal cell carcinoma will receive same sequential treatment strategy (Cabozantinib for 12 weeks, then proceed with Ipilimumab plus Nivolumab immunotherapy x4 over 12 weeks, then subsequent therapies depending on treatment response for another 12 weeks \[Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG\]).
Is the drug combination Cabozantinib, Ipilimumab, and Nivolumab promising for kidney cancer?Yes, the combination of Cabozantinib, Ipilimumab, and Nivolumab is promising for kidney cancer. Studies show that Cabozantinib and Nivolumab together can control the disease for a long time and improve survival rates. This combination is approved in many countries as a first-line treatment for advanced kidney cancer. The addition of Ipilimumab in trials suggests that using all three drugs together could be a new and effective option for patients.24789
What safety data is available for the sequential therapy in kidney cancer?The safety data for the sequential therapy involving cabozantinib, nivolumab, and ipilimumab in kidney cancer includes findings from several studies. The CheckMate 9ER study demonstrated that cabozantinib plus nivolumab had a manageable safety profile with appropriate management strategies such as prophylaxis, supportive care, dose modifications, and immunosuppressive therapy. Common adverse events included diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. Another study compared adverse events between cabozantinib plus nivolumab and ipilimumab plus nivolumab, highlighting differences in safety profiles. Overall, the safety profiles of these combinations are considered manageable with proper care and adjustments.356911
What data supports the idea that Sequential Therapy for Kidney Cancer is an effective treatment?The available research shows that combining cabozantinib with nivolumab is effective for treating advanced kidney cancer. In the CheckMate 9ER trial, this combination was better than using sunitinib alone, leading to longer periods without the disease getting worse and improved overall survival. Patients also reported a better quality of life with this combination. Additionally, the combination of nivolumab and ipilimumab has shown a higher response rate and better survival compared to sunitinib, especially for patients with a higher risk profile. These findings suggest that Sequential Therapy for Kidney Cancer is a strong option for treating this condition.178910
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain cancer treatments or immunosuppressive medications recently. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
Adults with advanced or metastatic clear cell renal cell carcinoma that can't be surgically removed. They should have a life expectancy of at least 12 weeks, measurable disease, and good organ function. Participants must not be pregnant, have had certain cancers within the last 3 years, or received specific treatments for kidney cancer before.Inclusion Criteria
I am 18 years old or older.
I had kidney cancer, underwent kidney removal, and now it has spread.
My kidney cancer cannot be cured with surgery or radiation and is mostly clear cell type.
I am fully active or able to carry out light work.
I can provide a tumor sample with a pathology report for testing.
Exclusion Criteria
I haven't had recent radiation or radionuclide treatments and have no ongoing complications from them.
I cannot swallow pills.
I have had an autoimmune disease in the last 2 years.
I have had cancer spread to the lining of my brain and spinal cord.
I am currently taking blood thinners.
I do not have any other cancer that needs treatment.
I received my last cancer treatment less than 4 weeks ago or within five half-lives of the treatment.
I had a severe reaction to previous immunotherapy, or I still have moderate side effects from it.
I have previously received treatments like cabozantinib or nivolumab for advanced kidney cancer.
I have not received a live vaccine within the last 30 days and do not plan to during the study.
Treatment Details
The study tests a sequence of drugs: Cabozantinib for 12 weeks followed by Ipilimumab plus Nivolumab immunotherapy over another 12 weeks. Depending on response, treatment may continue with either Nivolumab alone or in combination with Lenvatinib/Everolimus.
1Treatment groups
Experimental Treatment
Group I: Patients with metastatic or unresectable clear cell renal cell carcinomaExperimental Treatment5 Interventions
Patients with metastatic or unresectable clear cell renal cell carcinoma to receive same sequential treatment strategy. (Cabozantinib for 12 weeks, then proceed with Ipilimumab plus Nivolumab immunotherapy x4 over 12 weeks, then subsequent therapies depending on treatment response for another 12 weeks \[Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG\]).
Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:
πͺπΊ Approved in European Union as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
πΊπΈ Approved in United States as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
π¨π¦ Approved in Canada as Cabometyx for:
- Renal cell carcinoma
- Hepatocellular carcinoma
π―π΅ Approved in Japan as Cabometyx for:
- Renal cell carcinoma
Find a clinic near you
Research locations nearbySelect from list below to view details:
Icahn School of Medicine at Mount SinaiNew York, NY
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Who is running the clinical trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
References
[Immunotherapy for renal cell carcinoma - current status]. [2019]Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo®) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma after prior VEGF targeted therapy. Nivolumab in combination with Ipilimumab will become a standard 1st line option for patients with intermediate and high risk profile according to IMDC. Further data are required regarding PD-1/PD-L1 inhibitors in combination with Bevacizumab and VEGFR-TKIs, respectively, including overall survival and side effect profile.
Sequencing Therapies for Metastatic Renal Cell Carcinoma. [2020]In an era of several therapeutic options available, optimal treatment sequencing is crucial to providing patients the most effective therapy and promoting quality of life. In clear cell renal cell carcinoma, a combination approach with an immunotherapy backbone, such as nivolumab/ipilimumab or axitinib/pembrolizumab, has a key role in the first-line setting. Safety and activity data support the transition to single-agent targeted therapies in the second-line setting. Nivolumab monotherapy possesses clinical and mechanistic rationale as a second-line therapeutic option for patients treated with targeted therapies in the first-line setting. Gene expression models are being generated from large prospective clinical trial data sets.
Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. [2023]We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances.
An Illustrative Case of Combination Cabozantinib/Nivolumab for Progressive Metastatic Renal Cell Carcinoma (mRCC). [2022]We report a case using combination cabozantinib plus nivolumab to salvage disease control in a patient with refractory metastatic renal cell carcinoma. The patient had previously experienced disease progression from high-dose interleukin-2, sunitinib, pazopanib, cabozantinib, and nivolumab, all given sequentially. Combination cabozantinib plus nivolumab resulted in 22 months of disease control. Vascular endothelial growth factor inhibitors including cabozantinib have immunomodulatory effects when combined with immune checkpoint inhibitors, with multiple ongoing phase III trials exploring the cabozantinib plus nivolumab combination in the first-line setting. To our knowledge, this is the first reported case of progression on nivolumab and cabozantinib when given as sequential monotherapies but stable disease on combination cabozantinib plus nivolumab.
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.
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.
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.
Less is More? First Impressions From COSMIC-313. [2023]The COSMIC-313 phase 3 randomized controlled trial tested the triplet combination of cabozantinib with nivolumab and ipilimumab in comparison with nivolumab plus ipilimumab control as fist-line systemic therapy in metastatic clear cell renal cell carcinoma. The first results presented at the 2022 European Society of Medical Oncology Congress are a milestone for the renal cell carcinoma field because they signal the advent of triplet combinations as potential treatment options for our patients. The present commentary highlights some considerations and potential next steps based on these first impressions.
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.
Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. [2023]Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment.
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.