Navitoclax + Dabrafenib + Trametinib for Melanoma

Recruiting at52 trial locations

Overseen by Ryan J Sullivan

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with BRAF mutant melanoma or solid tumors that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Navitoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of tumor cells by blocking Bcl-2, a protein needed for tumor cell survival. Giving navitoclax, dabrafenib, and trametinib may help shrink tumors in patients with melanoma.

Research Team

Ryan J Sullivan

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

Adults with BRAF mutant melanoma that's spread or can't be surgically removed, who have good organ function and no recent significant bleeding or other serious illnesses. They must not have had certain treatments recently, agree to use non-hormonal birth control, and be able to swallow pills. Those with known allergies to the drugs being tested or similar compounds are excluded.

Inclusion Criteria

Your blood clotting tests should be within the normal range.

Your white blood cell count is equal to or greater than 3,000 per microliter.

You must have a certain amount of a type of white blood cell called neutrophils in your blood.

Exclusion Criteria

Patients who are receiving any other investigational agents have received any other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study

I am HIV-positive but not on any HIV medication that would interfere with the study drugs.

I have not taken navitoclax, BRAF, or MEK inhibitors.

Treatment Details

Interventions

• Dabrafenib; Trametinib (Protein Kinase Inhibitor)
• Navitoclax (B-cell lymphoma-2 (BCL-2) inhibitor)

Trial Overview The trial is testing a combination of three drugs: dabrafenib, trametinib, and navitoclax for advanced melanoma with a specific mutation (BRAF V600E/K). It aims to find the best dose and see how well these drugs work together in stopping cancer growth by blocking enzymes and proteins needed by cancer cells.

Participant Groups

Group I: Arm II (dabrafenib, trametinib, and navitoclax) Experimental Treatment 11 Interventions

Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

Group II: Arm I (dabrafenib, trametinib) Experimental Treatment 10 Interventions

ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

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