Highlights of the NCCN Oncology Research Program
The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program's establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.
NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.
An NCCN study funded through the grant mechanism is highlighted below.
A Phase II, Open-Label, 2-Arm Study of the MEK Inhibitor, Trametinib, to Investigate the Safety and Anticancer Activity in Subjects With Melanoma With BRAF Non-V600 Mutations
Principal Investigator: Douglas B. Johnson, MD, MSCI
Institutional Principal Investigators: Michael Davies, MD, PhD; Keith Flaherty, MD; and Suthee Rapisuwon, MD
Condition: Melanoma
Institutions: Vanderbilt-Ingram Cancer Center, The University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, and Georgetown University
This study is a phase II, open-label, multisite, 2-arm study designed to determine the activity and safety of the orally administered MEK inhibitor trametinib in subjects with melanoma harboring mutations in BRAF at locations other than codon 600 (atypical BRAF mutations; BRAF non-V600MUT) or BRAF fusions. More than 5% of melanomas harbor these atypical BRAF mutations or fusions. Early clinical and laboratory findings strongly support the use of MEK inhibitors for this population, although this has never been systematically studied.
In this study, all patients will receive trametinib, 2 mg orally administered once daily, and will be stratified into cohorts by mutation type for analysis purposes. Cohort A will consist of subjects with melanoma harboring mutations that have previously been described as sensitive to MEK inhibitors in preclinical and/or early clinical studies (L597, K601E, G469A, E586K, F595L) and BRAF fusions. Cohort B will consist of subjects with melanoma harboring mutations that have previously been shown to have low affinity for MEK phosphorylation from previous studies (eg, D594V, G466V, G496R), or with other mutations for which the sensitivity to MEK inhibitors is completely unknown.
Primary Objective:
Determine the clinical efficacy of trametinib in advanced BRAF non-V600MUT melanoma (“high activity” group)
Secondary Objectives:
Characterize the safety of trametinib
Evaluate the impact of trametinib on progression-free and overall survivals in patients with advanced BRAF non-V600MUT melanoma
Exploratory Objectives:
Determine the clinical efficacy of trametinib in advanced BRAF non-V600MUT melanoma (“low activity/unknown” group)
Identify mechanisms of resistance to trametinib in this patient population
Contact: Vanderbilt Cancer Clinical Trials Information Program • 800-811-8480
ClinicalTrials.gov Identifier: NCT02296112
The goal of the Highlights of the NCCN Oncology Research Program (ORP) is to provide readers with more information on the ORP, including studies currently accruing patients.
For more information on specific trials, including patient selection criteria, please use the contact information listed with each study.
For more information on the NCCN ORP, including a complete detailing of the clinical studies currently underway at NCCN Member Institutions, please access the NCCN ORP pages at NCCN.org/clinical_trials/clinicians.asp.
