FORT WASHINGTON, Pa.--(National Comprehensive Cancer Network® (NCCN®) Oncology Research Program (ORP) recently awarded 11 research grants to investigators following a review of proposals submitted in response to the NCCN Dabrafenib and Trametinib Request for Proposals. These grants were made possible through a $4-million research grant from GlaxoSmithKline to scientifically evaluate the clinical effectiveness of dabrafenib (GSK2118436) and trametinib (GSK1120212) in treatment of advanced melanoma and other cancers.)--The
“Randomized Phase II Trial of Single Agent MEK Inhibitor GSK1120212 vs. 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer”
“The NCCN ORP is pleased to have the opportunity to work with GlaxoSmithKline on the dabrafenib and trametinib research projects,” said Diane Paul, MS, RN, Vice President, NCCN ORP. “These 11 new studies—bringing the total ORP clinical trials to more than 70—afford the NCCN Member Institutions and their investigators the opportunity to identify breakthroughs in various cancer settings, and determine whether these drugs can improve patient outcomes.”
According to GlaxoSmithKline: Dabrafenib (GSK2118436) is an investigational, orally bioavailable, selective RAF kinase inhibitor (BRAF). Activating mutations in BRAF are present in approximately 50 percent of melanoma and approximately eight percent of all cancers. The mutation appears to have a direct role in activating the mitogen-activated protein (MAP) kinase pathway, which controls processes such as cell proliferation, differentiation, survival, and apoptosis (cell death).
Trametinib (GSK1120212) is also an investigational, orally bioavailable inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. MEK proteins are key components of the extracellular signal-related kinase (ERK) pathway, which is commonly hyper-activated in tumor cells. Constant and unregulated activation of this pathway has been implicated in many cancers. MEK 1/2 are thought to play a role in the activation of key signaling pathways that regulate cell growth.
The following proposals for dabrafenib have been awarded funding:
- Paul Chapman, MD, Memorial Sloan-Kettering Cancer Center, “A phase 2 Trial of Adjuvant Dabrafenib (GSK2118436) in Patients with Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K mutation”
- Mark Kelley, MD, MMHC, FACS, Vanderbilt-Ingram Cancer Center, “Biomarkers of Response and Resistance to Sequential B-RAF and MEK Targeted Therapy in a Pre-Surgical Model of Advanced, Operable Melanoma”
- Martin McMahon, PhD, UCSF Helen Diller Family Comprehensive Cancer Center, “Mechanisms of BRAF(V600E) Inhibitor Sensitivity or Resistance In Genetically Engineered Mouse Models Of Malignant Melanoma”
- Sareh Parangi, MD, Massachusetts General Hospital Cancer Center, “Accurate Modeling of Resistance to BRAF Inhibition in an Orthotopic Animal Model of Thyroid Cancer Progression”
- Manisha Shah, MD, The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, “A Randomized Phase 2 Study of Single Agent GSK2118436 (BRAFi) vs. Combination Regimen GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Patients with BRAF-Mutated Thyroid Carcinoma”
- Manisha Shah, MD, The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, “A Phase 1 Trial of GSK2118436 (BRAFi) and Pazopanib in Patients with BRAF-Mutated Advanced Malignant Tumors”
The following proposals for trametinib have been awarded funding:
- Adil Daud, MD, UCSF Helen Diller Comprehensive Cancer Center, “Phase I/II Clinical Trial of the MEK Inhibitor Trametinib with the PI3Kinase inhibitor GSK2126458 in BRAF Wild Type Melanoma”
- Richard Kim, MD, Moffit Cancer Center, “Randomized Phase II Trial of Single Agent MEK Inhibitor GSK1120212 vs. 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer”
- Andrea Myers, MD, PhD, Dana-Farber/Brigham and Women’s Cancer Center, “ A Single Arm, Single Stage Phase II Trial of GSK1120212 and GSK2126458 in Persistent or Recurrent Cervical Cancer”
- Ravindra Uppaluri, MD, PhD, Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, “A Phase II Window of Opportunity Trial with GSK1120212 in Surgically Resectable Oral Squamous Cell Cancer”
- Evan Wuthrick, MD, The Ohio State University Comprehensive Cancer Center- James Cancer Hospital and Solove Research Institute, “A Phase I Trial of MEK Inhibitor GSK1120212 in Combination with Neoadjuvent 5-Fluorouracil Chemoradiation in the Treatment of KRAS, BRAF, and NRAS-Mutant Rectal Cancers”
The awardees responded to a Request for Proposals issued by the NCCN ORP to the 21 NCCN Member Institutions. Submissions were peer reviewed by the NCCN Dabrafenib and Trametinib Scientific Review Committees. The awardees were selected based on several key criteria, including scientific merit, existing data, and the types of studies necessary to further evaluate the activity of dabrafenib and trametinib.
The NCCN ORP is organized to obtain funding to support scientifically meritorious research projects at NCCN Member Institutions. Policies and standards for the program were set by the NCCN Investigator Steering Committee, a group comprised of senior research physicians appointed by each NCCN Member Institution. The NCCN ORP has received more than $36 million in research grants from major pharmaceutical companies to support investigator-initiated trials. These trials explore new venues of clinical investigation that answer important scientific questions. Studies evaluate combinations and sequencing regimens of drugs, drug resistance, mechanisms of action of specific agents, or explore extended uses for scientific agents.
About the National Comprehensive Cancer Network
The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.
The NCCN Member Institutions are: City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; Moffitt Cancer Center, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute, Memphis, TN; Stanford Cancer Institute, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE; The University of Texas MD Anderson Cancer Center, Houston, TX; and Vanderbilt-Ingram Cancer Center, Nashville, TN.
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