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

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive18 and overARRAY-818-302
NCI-2016-01543, 2015-005805-35, NCT02928224

Trial Description

Summary

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.

Eligibility Criteria

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

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 CK

(e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis,

spinal muscular atrophy)

Residual 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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Array Biopharma Inc

  • Merck KgaA
  • Pierre Fabre Medicament

Trial Sites

U.S.A.

California
Duarte

City of Hope Comprehensive Cancer Center

Marwan Ghazi Fakih
Ph: 800-826-4673
Email: becomingapatient@coh.org

Marwan Ghazi Fakih
Principal Investigator

Los Angeles

USC / Norris Comprehensive Cancer Center

Heinz-Josef Lenz
Principal Investigator

Colorado
Aurora

University of Colorado Cancer Center - Anschutz Cancer Pavilion

Christopher Hanyoung Lieu
Principal Investigator

Illinois
Chicago

University of Chicago Comprehensive Cancer Center

Manish R. Sharma
Principal Investigator

Iowa
Iowa City

University of Iowa/Holden Comprehensive Cancer Center

Daniel James Berg
Principal Investigator

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

Nilofer Saba Azad
Principal Investigator

Ohio
Cleveland

Case Comprehensive Cancer Center

Alok Anand Khorana
Principal Investigator

Tennessee
Nashville

Vanderbilt University/Ingram Cancer Center

Dana Backlund Cardin
Principal Investigator

Texas
Houston

M D Anderson Cancer Center

Van Karlyle Morris
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT02928224

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.