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.

NCCN-sponsored studies funded through the grant mechanism are highlighted below.

A Phase 2 Trial of Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation

Principal Investigator: Paul Chapman, MD

Condition: Melanoma

Institution: Memorial Sloan-Kettering Cancer Center

Inhibition of BRAFV600E kinase has emerged as an effective therapeutic strategy for patients with metastatic melanoma harboring a BRAFV600E mutation. It is reasonable to speculate that BRAFV600E kinase inhibitors will benefit molecularly selected patients with melanoma at earlier stages of the disease. Patients with stage IIIC melanoma are at an extremely high risk for disease recurrence and death despite definitive surgical resection. In this single-center phase II trial, patients with surgically resected stage IIIC melanoma characterized by a BRAFV600E or BRAFV600K mutation will be treated with 4 cycles of adjuvant dabrafenib and monitored clinically and radiographically for disease recurrence for 24 months.

Primary Objective:

• Determine the relapse-free survival (RFS) at 24 months for patients with stage IIIC melanoma harboring a BRAFV600E/K mutation who are treated with definitive surgical resection followed by 4 cycles of adjuvant dabrafenib administration.

Secondary Objective:

• Determine overall survival.

Exploratory Objectives:

• Characterize the genetic heterogeneity of BRAF-mutated melanomas and explore mechanisms of intrinsic and acquired resistance to dabrafenib.

• Evaluate the ability of circulating tumor-derived exosomes to predict melanoma recurrence.

Contacts: Paul Chapman, MD • 646-888-4162

Jedd Wolchok, MD, PhD • 646-888-2395

ClinicalTrials.gov Identifier: NCT01682213

A Phase I Trial of Vorinostat Concurrent With Stereotactic Radiotherapy in Treatment of Brain Metastases From Non–Small Cell Lung Cancer

Principal Investigator: Griffith Harsh, MD

Conditions: Brain metastases; non–small cell lung cancer

Institution: Stanford Cancer Institute, and Moffitt Cancer Center

Vorinostat is an oral histone deacetylase inhibitor with anticancer activity in several different cancers. Given the potentially debilitating negative effects and the lack of survival benefit of whole brain irradiation for treatment of brain metastases, there is a growing movement toward using stereotactic radiosurgery (SRS) alone for patients with a limited number of brain metastases. The hypothesis behind this study is that vorinostat, given concurrently with SRS, will improve local tumor control and decrease distant brain failure. The purpose of this study is to determine the maximum tolerated dose (MTD) of vorinostat given concurrently with SRS to treat non–small cell lung cancer brain metastases in patients with 1 to 4 lesions.

Primary Objective Phase I:

• Determine the MTD of vorinostat given concurrently with SRS to treat brain metastases in patients with 1 to 4 lesions.

Primary Objective Expanded Phase I:

• Confirm safety of the MTD.

• Determine the local control rate.

• Determine the distant intracranial control rate.

Secondary Objectives:

• Determine the short-term (<30 days posttreatment) and long-term (>30 days posttreatment) adverse effects.

• Determine the overall survival rate.

Contacts: Maria Coburn • 650-736-9551 • mcoburn@stanford.edu

Melissa Joiner, RN, CRC • 813-745-1896 • melissa.joiner@moffitt.org

ClinicalTrials.gov Identifier: NCT00946673