Cabozantinib + Nivolumab for Advanced Skin and Head & Neck Cancers

Recruiting in Palo Alto (17 mi)

+222 other locations

Overseen by Siwen Hu-Lieskovan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Research Team

Siwen Hu-Lieskovan

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

Adults with advanced melanoma or squamous cell head and neck cancer that has spread, who have progressed after PD-1 checkpoint therapy. They must be able to take oral medication, have measurable disease, known HPV/p16 status for oropharyngeal cancer, adequate organ function and performance status. Exclusions include prior anti-VEGF therapies, active autoimmune diseases requiring steroids, significant infections or organ dysfunction.

Inclusion Criteria

I haven't had serious heart problems in the last 3 months.

My organs function well enough for treatment.

I do not take steroids or other drugs for an autoimmune disease, with some exceptions.

Exclusion Criteria

Participants must not have received investigational agents or monoclonal antibodies within 28 days prior to step 2 registration

I haven't had cancer treatment or steroids in the last 14 days.

I haven't taken certain medications that affect enzyme levels recently.

Treatment Details

Interventions

• Cabozantinib S-malate (Tyrosine Kinase Inhibitor)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The trial is testing the combination of Cabozantinib (an enzyme blocker) and Nivolumab (an immunotherapy antibody) on patients with certain types of advanced cancers. It aims to see if these drugs can shrink or stabilize tumors based on biomarkers like 'tumor mutational burden' and 'tumor inflammation signature'.

Participant Groups

Group I: Treatment (nivolumab and cabozantinib) Experimental Treatment 6 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cabozantinib PO daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School