NCT04527549

Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma

The BAMM2 (BRAF, Autophagy, MEK Inhibition in Melanoma) Study: A Randomized Double Blind Phase II Study of Dabrafenib and Trametinib With or Without Hydroxychloroquine in Advanced BRAF V600E/K Melanoma With Elevated LDH

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: ECOG-ACRIN Cancer Research Group · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial investigates how well adding hydroxychloroquine to the standard treatment of dabrafenib and trametinib works to overcome resistance and delay disease progression in treating patients with stage IIIC or IV BRAF V600E/K melanoma. Hydroxychloroquine may cause cell death in tumor cells that rely on a process called "autophagy" for survival. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hydroxychloroquine together with dabrafenib and trametinib may work better than dabrafenib and trametinib alone to shrink and stabilize the cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the rate of one year progression-free survival (PFS) when hydroxychloroquine sulfate (hydroxychloroquine) or placebo is added to dabrafenib mesylate (dabrafenib) and trametinib dimethyl sulfoxide (trametinib) in advanced BRAFV600E/K melanoma with elevated lactate dehydrogenase (LDH). SECONDARY OBJECTIVES: I. To compare the PFS of both arms. II. To evaluate the best overall response rate by treatment arm. III. To evaluate the complete response (CR) rate by treatment arm. IV. To evaluate the adverse event rate by treatment arm. V. To evaluate overall survival (OS) by treatment arm. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive dabrafenib mesylate orally (PO) twice daily (BID), trametinib dimethyl sulfoxide PO once daily (QD), and hydroxychloroquine sulfate PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive dabrafenib mesylate PO BID, trametinib dimethyl sulfoxide PO QD, and placebo PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 1 year.

Conditions

• Clinical Stage IV Cutaneous Melanoma AJCC v8
• Locally Advanced Melanoma
• Pathologic Stage IIIC Cutaneous Melanoma AJCC v8
• Pathologic Stage IV Cutaneous Melanoma AJCC v8
• Unresectable Melanoma

Interventions

Type	Name	Description
DRUG	Dabrafenib mesylate	Given PO
DRUG	Hydroxychloroquine	Given PO
DRUG	Placebo Administration	Given PO
DRUG	Trametinib dimethyl sulfoxide	Given PO

Timeline

• Start date: 2021-06-01
• Primary completion: 2024-01-08
• Completion: 2024-01-08
• First posted: 2020-08-26
• Last updated: 2026-04-01
• Results posted: 2024-08-22

Locations

199 sites across 1 country: United States

Regulatory

• FDA-regulated drug study