Protocol No.

142813 (10285)

Principal Investigator

Hu-Lieskovan, Siwen

Phase

I/II

Age Group

Adult

ClinicalTrials.Gov

NCT04557956 (Click to jump to clinicaltrials.gov)

Eligibility Detail

Eligibility Criteria.pdf

Contact

Nina Orr
+1 801-213-4266
nina.orr@hci.utah.edu

Title

Phase I/II Study of an EZH2 Inhibitor (Tazemetostat) in Combination with Dual BRAF/MEK Inhibition in Patients with BRAF-Mutated Metastatic Melanoma Who Progressed On Prior BRAF/MEK Inhibitor Therapy

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.

• Phase 1: To observe and record anti-tumor activity. Although the clinical benefit of this drug combination has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus patients will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.
• Phase 2: To determine the overall response rate of single-agent EZH2 inhibitor therapy (tazemetostat) and triplet EZH2 inhibitor (tazemetostat), BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) therapy in patients with BRAF/MEK inhibitor-resistant BRAFV600-mutated melanomas harboring an EZH2 alteration.

• To explore alterations in the gene expression profile (RNA-sequencing), H3K27methylome (IHC, ChIP-Sequencing), and open chromatin landscape (ATAC-Sequencing) with EZH2 inhibition in fresh clinical or PDX-derived tumor samples, which may reveal underlying transcriptional/epigenetic pathways mediating response to treatment.

Applicable Disease Sites

Melanoma

Participating Institutions

Huntsman Cancer Institute : Nina Orr; University of Utah : Nina Orr

Status

Open