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Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan / Cetuximab or Infusional 5-Fluorouracil (5-FU) / Folinic Acid (FA) / Irinotecan (FOLFIRI) / Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer

Trial Status: Closed to Accrual

This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan / cetuximab or FOLFIRI / cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.

Inclusion Criteria

  • Age ≥ 18 years at time of informed consent
  • Histologically- or cytologically-confirmed CRC that is metastatic
  • Presence of BRAFV600E in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory
  • Progression of disease after 1 or 2 prior regimens in the metastatic setting
  • Evidence of measurable or evaluable non-measurable disease per RECIST, v1.1
  • Adequate bone marrow, cardiac, kidney and liver function
  • Able to take oral medications
  • Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential
  • Males must agree to take appropriate precautions to avoid fathering a child from screening through follow-up

Exclusion Criteria

  • Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab, panitumumab or other epidermal growth factor receptor (EGFR) inhibitors
  • Prior irinotecan hypersensitivity or toxicity that would suggest an inability to tolerate irinotecan 180 mg/m2 every 2 weeks
  • Symptomatic brain metastasis or leptomeningeal disease
  • History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
  • Known history of acute or chronic pancreatitis
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤12 months prior to randomization
  • Uncontrolled blood pressure despite medical treatment
  • Impaired GI function or disease that may significantly alter the absorption of encorafenib or binimetinib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption)
  • Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
  • History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli
  • Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phosphor)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Residual common terminology criteria for adverse events (CTCAE) ≥ Grade 2 toxicity from any prior anticancer therapy, with the exception of Grade 2 alopecia or Grade 2 neuropathy
  • Known history of HIV infection
  • Active hepatitis B or hepatitis C infection
  • Known history of Gilbert's syndrome
  • Known contraindication to receive cetuximab or irinotecan at the planned doses

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: CLOSED_TO_ACCRUAL

California

Duarte
City of Hope Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Marwan Ghazi Fakih
Phone: 800-826-4673
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Colorado

Aurora
University of Colorado Hospital
Status: CLOSED_TO_ACCRUAL

Connecticut

New Haven
Yale University
Status: CLOSED_TO_ACCRUAL
Contact: Kamil Sadowski
Phone: 203-785-6661

Florida

Jacksonville
Mayo Clinic in Florida
Status: CLOSED_TO_ACCRUAL

Georgia

Atlanta
Emory Saint Joseph's Hospital
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Emory University Hospital / Winship Cancer Institute
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Emory University Hospital Midtown
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Contact: Matthew Truman Edison
Phone: 317-274-5725

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Kansas

Fairway
University of Kansas Clinical Research Center
Status: CLOSED_TO_ACCRUAL
Kansas City
University of Kansas Cancer Center
Status: CLOSED_TO_ACCRUAL
Westwood
University of Kansas Hospital-Westwood Cancer Center
Status: CLOSED_TO_ACCRUAL

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: CLOSED_TO_ACCRUAL

Minnesota

Rochester
Mayo Clinic in Rochester
Status: CLOSED_TO_ACCRUAL

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: CLOSED_TO_ACCRUAL

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: COMPLETED

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

New York

New York
Memorial Sloan Kettering Cancer Center
Status: CLOSED_TO_ACCRUAL

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Oregon

Portland
OHSU Knight Cancer Institute
Status: CLOSED_TO_ACCRUAL

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: CLOSED_TO_ACCRUAL

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: CLOSED_TO_ACCRUAL

Texas

Houston
M D Anderson Cancer Center
Status: CLOSED_TO_ACCRUAL

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: CLOSED_TO_ACCRUAL

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Pfizer Inc

  • Primary ID ARRAY-818-302
  • Secondary IDs NCI-2016-01543, 2015-005805-35, BEACON CRC, C4221009
  • Clinicaltrials.gov ID NCT02928224