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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

NCT02928224

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: A Multicenter, Randomized, Open-label, 3-Arm Phase 3 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

Clinical Trial IDs

  • ORG STUDY ID: ARRAY-818-302
  • SECONDARY ID: 2015-005805-35
  • NCT ID: NCT02928224

Conditions

  • BRAF V600E-mutant Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
EncorafenibSafety Lead-in, Triplet Arm
BinimetinibSafety Lead-in, Triplet Arm
CetuximabSafety Lead-in, Triplet Arm
IrinotecanControl Arm
Folinic AcidFAControl Arm
5-Fluorouracil5-FUControl Arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Safety Lead-in, Triplet ArmExperimentalEncorafenib + binimetinib + cetuximab.
  • Encorafenib
  • Binimetinib
  • Cetuximab
Doublet ArmExperimentalEncorafenib + cetuximab.
  • Encorafenib
  • Cetuximab
Control ArmActive ComparatorInvestigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
  • Cetuximab
  • Irinotecan
  • Folinic Acid
  • 5-Fluorouracil

Eligibility Criteria

        Key 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

        Key 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:(Safety Lead-in) Incidence of dose-limiting toxicities (DLTs)
Time Frame:Cycle 1 (up to 28 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:(Safety Lead-in) Response Rate (ORR)
Time Frame:Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Safety Lead-in) Duration of Response (DOR)
Time Frame:Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Safety Lead-in) Time to Response
Time Frame:Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm and Triplet Arm vs. Doublet Arm
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Comparison of Progression-free Survival (PFS) in study arms
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Comparison of Objective Response Rate (ORR) in study arms
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Comparison of Duration of Response (DOR) in study arms
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Comparison of Time to Response in study arms
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Incidence and severity of adverse events (AEs) and changes in clinical laboratory parameters, vital signs, electrocardiograms (ECGs), echocardiogram (ECHO)/multi-gated acquisition (MUGA) scans and ophthalmic examinations
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Phase 3) Comparison of the Quality of Life in study arms
Time Frame:Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Safety Issue:
Description:
Measure:(Safety Lead-in) Evaluation of the area under the concentration-time curve (AUC) for cetuximab, encorafenib, binimetinib, and a metabolite of binimetinib
Time Frame:Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Safety Issue:
Description:
Measure:(Safety Lead-in) Evaluation of the maximum concentration (Cmax) for cetuximab, encorafenib, binimetinib, and a metabolite of binimetinib
Time Frame:Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Safety Issue:
Description:
Measure:(Safety Lead-in) Evaluation of the time of maximum observed concentration (Tmax) for cetuximab, encorafenib, binimetinib, and a metabolite of binimetinib
Time Frame:Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Safety Issue:
Description:
Measure:(Safety Lead-in) Evaluation of the steady-state concentration measured just before the next dose of study drug (Ctrough) for cetuximab, encorafenib, binimetinib, and a metabolite of binimetinib
Time Frame:Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Array BioPharma

Trial Keywords

  • Colorectal cancer
  • BRAF
  • BRAFV600E

Last Updated

February 9, 2018