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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02928224




Registration number
NCT02928224
Ethics application status
Date submitted
16/08/2016
Date registered
10/10/2016

Titles & IDs
Public 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
Scientific 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
Secondary ID [1] 0 0
BEACON CRC
Secondary ID [2] 0 0
ARRAY-818-302
Universal Trial Number (UTN)
Trial acronym
BEACON CRC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
BRAF V600E-mutant Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Encorafenib
Treatment: Drugs - Binimetinib
Treatment: Drugs - Cetuximab
Treatment: Drugs - Irinotecan
Treatment: Drugs - Folinic Acid
Treatment: Drugs - 5-Fluorouracil

Experimental: Safety Lead-in, Triplet Arm - Encorafenib + binimetinib + cetuximab.

Experimental: Doublet Arm - Encorafenib + cetuximab.

Active comparator: Control Arm - Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.


Treatment: Drugs: Encorafenib
Orally, once daily.

Treatment: Drugs: Binimetinib
Orally, twice daily.

Treatment: Drugs: Cetuximab
Standard of care.

Treatment: Drugs: Irinotecan
Standard of care.

Treatment: Drugs: Folinic Acid
Standard of care.

Treatment: Drugs: 5-Fluorouracil
Standard of care.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
(Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 (up to 28 days)
Primary outcome [2] 0 0
(Safety Lead-in) Number of Participants With Adverse Events (AEs)
Timepoint [2] 0 0
Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Primary outcome [3] 0 0
(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis
Timepoint [3] 0 0
Duration of safety lead-in, approximately 6 months (up to 28 days per cycle)
Primary outcome [4] 0 0
(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis
Timepoint [4] 0 0
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)
Primary outcome [5] 0 0
(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis
Timepoint [5] 0 0
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm)
Primary outcome [6] 0 0
(Phase 3) Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm
Timepoint [6] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [1] 0 0
(Safety Lead-in) Objective Response Rate (ORR) by Investigator
Timepoint [1] 0 0
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)
Secondary outcome [2] 0 0
(Safety Lead-in) Objective Response Rate (ORR) by BICR
Timepoint [2] 0 0
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks)
Secondary outcome [3] 0 0
(Safety Lead-in) Duration of Response (DOR) by Investigator
Timepoint [3] 0 0
From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)
Secondary outcome [4] 0 0
(Safety Lead-in) Duration of Response (DOR) by BICR
Timepoint [4] 0 0
From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks)
Secondary outcome [5] 0 0
(Safety Lead-in) Time to Response by Investigator
Timepoint [5] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks)
Secondary outcome [6] 0 0
(Safety Lead-in) Time to Response by BICR
Timepoint [6] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks)
Secondary outcome [7] 0 0
(Safety Lead-in) Progression-Free Survival (PFS) by Investigator
Timepoint [7] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks)
Secondary outcome [8] 0 0
(Safety Lead-in) Progression-Free Survival (PFS) by BICR
Timepoint [8] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks)
Secondary outcome [9] 0 0
(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm
Timepoint [9] 0 0
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm)
Secondary outcome [10] 0 0
(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm
Timepoint [10] 0 0
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 89.1 weeks for triplet arm)
Secondary outcome [11] 0 0
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR
Timepoint [11] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [12] 0 0
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator
Timepoint [12] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [13] 0 0
(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR
Timepoint [13] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [14] 0 0
(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator
Timepoint [14] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [15] 0 0
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR
Timepoint [15] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [16] 0 0
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator
Timepoint [16] 0 0
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [17] 0 0
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator
Timepoint [17] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [18] 0 0
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR
Timepoint [18] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [19] 0 0
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator
Timepoint [19] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [20] 0 0
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR
Timepoint [20] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [21] 0 0
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator
Timepoint [21] 0 0
Duration of Phase 3, approximately 6 months (up to 28 days per cycle)
Secondary outcome [22] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR
Timepoint [22] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [23] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator
Timepoint [23] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [24] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR
Timepoint [24] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [25] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator
Timepoint [25] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [26] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR
Timepoint [26] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [27] 0 0
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator
Timepoint [27] 0 0
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [28] 0 0
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR
Timepoint [28] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [29] 0 0
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator
Timepoint [29] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm)
Secondary outcome [30] 0 0
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR
Timepoint [30] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [31] 0 0
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator
Timepoint [31] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm)
Secondary outcome [32] 0 0
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR
Timepoint [32] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [33] 0 0
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator
Timepoint [33] 0 0
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm)
Secondary outcome [34] 0 0
(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Timepoint [34] 0 0
Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)
Secondary outcome [35] 0 0
(Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Timepoint [35] 0 0
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)
Secondary outcome [36] 0 0
(Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Timepoint [36] 0 0
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)
Secondary outcome [37] 0 0
(Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet
Timepoint [37] 0 0
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days)
Secondary outcome [38] 0 0
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab
Timepoint [38] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [39] 0 0
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib
Timepoint [39] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [40] 0 0
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib
Timepoint [40] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [41] 0 0
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032)
Timepoint [41] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [42] 0 0
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab
Timepoint [42] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [43] 0 0
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib
Timepoint [43] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [44] 0 0
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib
Timepoint [44] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [45] 0 0
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032)
Timepoint [45] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [46] 0 0
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab
Timepoint [46] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [47] 0 0
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib
Timepoint [47] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [48] 0 0
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib
Timepoint [48] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [49] 0 0
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032)
Timepoint [49] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [50] 0 0
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib
Timepoint [50] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [51] 0 0
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib
Timepoint [51] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [52] 0 0
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab
Timepoint [52] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [53] 0 0
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib
Timepoint [53] 0 0
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days)
Secondary outcome [54] 0 0
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib
Timepoint [54] 0 0
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)
Secondary outcome [55] 0 0
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib
Timepoint [55] 0 0
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)
Secondary outcome [56] 0 0
(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab
Timepoint [56] 0 0
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days)
Secondary outcome [57] 0 0
Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Timepoint [57] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [58] 0 0
Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Timepoint [58] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [59] 0 0
Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters
Timepoint [59] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [60] 0 0
Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities
Timepoint [60] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [61] 0 0
Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values
Timepoint [61] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [62] 0 0
Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score
Timepoint [62] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)
Secondary outcome [63] 0 0
Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment
Timepoint [63] 0 0
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks)

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/10/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/11/2022
Sample size
Target
Accrual to date
Final
702
Recruitment in Australia
Recruitment state(s)
NEW South Wales (nsw)QLD,SA,VIC
Recruitment hospital [1] 0 0
St Vincent's Clinic - Darlinghurst
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Marsden Eye Specialists - Parramatta
Recruitment hospital [4] 0 0
Newcastle Eye Centre - Sydney
Recruitment hospital [5] 0 0
Mater Misericordiae Limited - South Brisbane
Recruitment hospital [6] 0 0
Central Adelaide Local Health Network Inc. operating as Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 0 0
Central Adelaide Local Health Network Inc. operating as The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [9] 0 0
Monash Health Translation Precinct - Monash Health - Clayton
Recruitment hospital [10] 0 0
Austin Health - Heidelberg
Recruitment hospital [11] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2150 - Parramatta
Recruitment postcode(s) [3] 0 0
2300 - Sydney
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
5042 - Bedford Park
Recruitment postcode(s) [7] 0 0
5011 - Woodville South
Recruitment postcode(s) [8] 0 0
3168 - Clayton
Recruitment postcode(s) [9] 0 0
3084 - Heidelberg
Recruitment postcode(s) [10] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
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France
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France
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France
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Germany
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Germany
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Bayern
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Germany
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Germany
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Germany
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Nordrhein-westfalen
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Germany
State/province [75] 0 0
North Rhine Westfalia
Country [76] 0 0
Germany
State/province [76] 0 0
Rheinland-pfalz
Country [77] 0 0
Germany
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Berlin
Country [78] 0 0
Germany
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Dresden
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Germany
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Hamburg
Country [80] 0 0
Hungary
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Zala
Country [81] 0 0
Hungary
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Budapest
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Hungary
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Debrecen
Country [83] 0 0
Hungary
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Pecs
Country [84] 0 0
Israel
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NAP
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Israel
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Ashkelon
Country [86] 0 0
Israel
State/province [86] 0 0
Be'er-Sheva
Country [87] 0 0
Israel
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Bnei Brak
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Israel
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Petah Tikva
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Israel
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Tel-Hashomer
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Italy
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CR
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Malatya
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Kyivska Oblast'
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Ukraine
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Zakarpats'ka Oblast'
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United Kingdom
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Berkshire
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United Kingdom
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Glasglow City, Scotland
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London
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Pierre Fabre Medicament
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Ono Pharmaceutical Co. Ltd
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02928224