Title
Phase 1/2 Study of EZH2 Inhibitor (Tazemetostat) In Comboination with Dual BRAF/MEK Inhibition in Patients with BRAF- Mutated Metastatic Melanoma Who Progressed On Prior BRAF/MEK Inhibitor Therapy

Description
This phase I/II trial investigates the best dose, possible benefits and/or side effects of tazemetostat in combination with dabrafenib and trametinib in treating patients with melanoma that has a specific mutation in the BRAF gene (BRAFV600) and that has spread to other places in the body (metastatic). Tazemetostat, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving tazemetostat in combination with dabrafenib and trametinib may stabilize BRAFV600 mutated melanoma.

Objective
Phase 1: To identify a maximum tolerated dose for the EZH2 inhibitor, tazemetostat, when used in combination with dual BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) therapy in BRAF/MEK inhibitor-resistant, BRAFV600-mutated metastatic melanoma.
Phase 2: To determine if the addition of the EZH2 inhibitor, tazemetostat, to BRAF and MEK inhibitor therapy improves progression-free survival over single-agent EZH2 inhibitor therapy in patients with BRAF/MEK inhibitor-resistant, BRAFV600-mutated melanomas harboring an EZH2 alteration.

Treatment Active Comparator: ARM I (tazemetostat) phase II
Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At the time of progression, patients may crossover to Arm II after completion of radiation therapy.
Experimental: ARM II (tazemetostat, dabrafenib, trametinib) phase I/phase II
Patients receive tazemetostat orally PO BID, 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.

Key Eligibility For full study eligibility, please see this study's ClinicialTrials.gov record.

Applicable Disease Sites
Melanoma/Skin cancer

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital