20 Participants Needed

Sequential Therapy for Kidney Cancer

CT
Overseen ByChe-Kai Tsao, MD
Age: 18+
Sex: Any
Trial Phase: Phase < 1
Sponsor: Icahn School of Medicine at Mount Sinai
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain cancer treatments or immunosuppressive medications recently, and some anticoagulants are not allowed. It's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug combination used in the Sequential Therapy for Kidney Cancer trial?

Research shows that the combination of cabozantinib and nivolumab is effective for advanced kidney cancer, leading to longer survival and better quality of life compared to other treatments. Additionally, combining nivolumab with ipilimumab has shown improved survival rates and response in patients with certain risk profiles.12345

Is the sequential therapy for kidney cancer safe for humans?

The combination of cabozantinib and nivolumab, sometimes with ipilimumab, has been studied for safety in treating advanced kidney cancer. While the safety profile is generally manageable, some side effects like diarrhea, liver issues, skin reactions, and fatigue can occur, but they can often be managed with supportive care and dose adjustments.26789

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

This drug combination is unique because it combines a tyrosine kinase inhibitor (Cabozantinib) with two immune checkpoint inhibitors (Nivolumab and Ipilimumab), offering a novel approach that may enhance the immune system's ability to fight cancer and improve outcomes compared to traditional treatments. The combination has shown promise in clinical trials, potentially leading to longer disease control and improved survival for patients with advanced kidney cancer.2451011

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 \[Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG\]).

Research Team

CT

Che-Kai Tsao

Principal Investigator

Investigator

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

Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception during the course of the study and for 4 months after the last dose of study treatment
Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
I had kidney cancer, underwent kidney removal, and now it has spread.
See 9 more

Exclusion Criteria

I haven't taken any kinase inhibitor medication in the last 2 weeks.
I haven't had recent radiation or radionuclide treatments and have no ongoing complications from them.
You have had a bad reaction to certain medications or their ingredients in the past.
See 20 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Cabozantinib

Participants receive Cabozantinib for 12 weeks

12 weeks

Treatment - Ipilimumab + Nivolumab

Participants receive Ipilimumab plus Nivolumab immunotherapy for 12 weeks

12 weeks

Treatment - Response-based

Participants receive Nivolumab for CR/PR/SD, or Cabozantinib or Lenvatinib/Everolimus for PROG for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Cabozantinib
  • Everolimus
  • Ipilimumab
  • Lenvatinib
  • Nivolumab
Trial Overview 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.
Participant Groups
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:

🇪🇺
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

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials
933
Recruited
579,000+

Findings from Research

Nivolumab (Opdivo®) has been established as an effective second-line treatment for metastatic renal cell carcinoma (mRCC), showing improved overall survival (26 months vs. 19.7 months) and response rates compared to Everolimus, based on the CheckMate 025 trial with 1,080 participants.
The combination of Nivolumab and Ipilimumab has demonstrated a significantly higher objective response rate (42% vs. 27%) and better overall survival in intermediate and high-risk patients compared to Sunitinib, while also improving quality of life, despite an increase in immune-related adverse events.
[Immunotherapy for renal cell carcinoma - current status].Grimm, MO., Foller, S.[2019]
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]
In a phase 3 trial involving 522 patients with metastatic renal cell carcinoma, adding atezolizumab to cabozantinib did not significantly improve progression-free survival or overall survival compared to cabozantinib alone, indicating that this combination may not be effective for patients whose disease progressed after immune checkpoint inhibitors.
The combination treatment with atezolizumab and cabozantinib resulted in higher rates of serious adverse events (48% vs. 33% for cabozantinib alone), suggesting increased toxicity without clinical benefit, which raises concerns about its use outside of clinical trials.
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.Pal, SK., Albiges, L., Tomczak, P., et al.[2023]

References

[Immunotherapy for renal cell carcinoma - current status]. [2019]
Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [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]
Cabozantinib plus Nivolumab: A Review in Advanced Renal Cell Carcinoma. [2022]
Less is More? First Impressions From COSMIC-313. [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]
Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors. [2023]
An Illustrative Case of Combination Cabozantinib/Nivolumab for Progressive Metastatic Renal Cell Carcinoma (mRCC). [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Sequencing Therapies for Metastatic Renal Cell Carcinoma. [2020]
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