1175 Participants Needed

Immunotherapy + Cabozantinib for Advanced Kidney Cancer

Recruiting at 972 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive drugs and specific anticoagulants are not allowed. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

What data supports the effectiveness of the drug combination of immunotherapy and cabozantinib for advanced kidney cancer?

Research shows that the combination of cabozantinib and nivolumab is effective for treating advanced kidney cancer, with studies indicating it leads to longer survival and better quality of life compared to some other treatments. This combination is recommended in both European and American guidelines for first-line treatment of advanced renal cancer.12345

Is the combination of immunotherapy and cabozantinib safe for advanced kidney cancer?

The combination of cabozantinib and nivolumab has been studied for advanced kidney cancer, showing a manageable safety profile with common side effects like diarrhea, fatigue, and skin reactions. These side effects can often be managed with supportive care and dose adjustments.13678

How is the drug combination of Ipilimumab, Nivolumab, and Cabozantinib unique for advanced kidney cancer?

This drug combination is unique because it combines immunotherapy (Ipilimumab and Nivolumab) with a targeted therapy (Cabozantinib), which is a tyrosine kinase inhibitor. This approach aims to enhance the immune system's ability to fight cancer while simultaneously targeting specific pathways that help cancer cells grow, offering a potentially more effective treatment for advanced kidney cancer compared to traditional therapies.12345

What is the purpose of this trial?

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 with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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.

Research Team

TZ

Tian Zhang

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

This trial is for adults with advanced kidney cancer that hasn't been treated yet. Participants should have a certain level of physical fitness (Karnofsky performance status >= 70%), measurable disease, and be at an intermediate or poor risk according to specific criteria. They can't join if they've had certain treatments before, have active autoimmune diseases, uncontrolled conditions like hypertension or infections like HIV with detectable viral load, or are pregnant.

Inclusion Criteria

You have a disease that can be measured according to the study's guidelines.
My kidney cancer is classified as intermediate or poor risk.
Your hemoglobin level is at least 8 grams per deciliter.
See 20 more

Exclusion Criteria

I haven't had serious stomach or bowel problems in the last 6 months.
I am currently being treated for an autoimmune disease.
Your blood pressure is too high and not under control.
See 22 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive nivolumab and ipilimumab intravenously every 21 days for up to 4 cycles

12 weeks
4 visits (in-person)

Treatment

Patients receive either nivolumab alone or nivolumab with cabozantinib based on randomization, with treatment repeating every 28 days

Ongoing until disease progression or unacceptable toxicity
Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

  • Cabozantinib
  • Ipilimumab
  • Nivolumab
Trial Overview The study compares standard immunotherapy treatment using Nivolumab and Ipilimumab followed by Nivolumab alone versus the same regimen followed by a combination of Nivolumab with Cabozantinib. The goal is to see if adding Cabozantinib improves outcomes in untreated renal cell carcinoma that has spread.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm B (nivolumab, cabozantinib)Experimental Treatment8 Interventions
INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity. Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD rwith clinical stability eceive nivolumab IV over 30 minutes on day 1 and cabozantinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.
Group II: Arm A (nivolumab)Active Control8 Interventions
INDUCTION: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. TREATMENT: Patients with iuPD with clinical instability receive cabozantinib PO daily on days 1-28. Treatment repeats every 28 days until further disease progression or unacceptable toxicity Patients with iCR receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with non-CR/non-PD with clinical stability receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI and blood and urine sample collection, and may also undergo a bone scan as clinically indicated throughout the study.

Ipilimumab is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Yervoy for:
  • Advanced melanoma
  • Stage III unresectable melanoma
  • Stage IV metastatic melanoma
🇪🇺
Approved in European Union as Yervoy for:
  • Advanced melanoma
  • Stage III unresectable melanoma
  • Stage IV metastatic melanoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a phase II trial involving 47 patients with advanced non-clear-cell renal cell carcinoma, the combination of cabozantinib and nivolumab showed a promising objective response rate of 47.5% in patients with papillary, unclassified, or translocation-associated RCC, along with a median progression-free survival of 12.5 months.
The treatment was less effective in chromophobe RCC, with no objective responses observed, highlighting the need for further research into genomic predictors of response, particularly mutations like NF2 and FH that were associated with better outcomes.
Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates.Lee, CH., Voss, MH., Carlo, MI., et al.[2023]
The combination of cabozantinib (a TKI) and nivolumab (an anti-PD-1 antibody) is an effective first-line treatment for previously-untreated advanced renal cell carcinoma (RCC), showing significantly longer progression-free and overall survival compared to sunitinib monotherapy in the CheckMate 9ER trial.
Patients receiving cabozantinib plus nivolumab reported better health-related quality of life, although the combination therapy had a higher incidence of serious adverse events compared to sunitinib, indicating a need for careful monitoring.
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma.Markham, A.[2022]
In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.
However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma.Choueiri, TK., Powles, T., Albiges, L., et al.[2023]

References

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]
Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab. [2023]
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]
Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]
Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]
Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]
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