A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer

Conditions

• Neoplasms

Eligibility Criteria

Sex

ALL

Age

16 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Encorafenib — DRUG
  75 mg capsules
• Cetuximab — DRUG
  Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
• Oxaliplatin — DRUG
  Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
• Irinotecan — DRUG
  Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
• Leucovorin — DRUG
  Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
• 5-FU — DRUG
  Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
• Capecitabine — DRUG
  150 mg or 500 mg Tablet
• Bevacizumab — DRUG
  Optional Injection for intravenous use 100 mg/vial or 400 mg/vial

Study Details

The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab) taken alone or together with standard chemotherapy for the potential treatment of colorectal cancer that: * has spread to other parts of the body (metastatic); * has a certain type of abnormal gene called "BRAF"; and * has not received prior treatment. Participants in this study will receive one of the following study treatments: * Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection into the vein) at the study clinic. * Encorafenib plus cetuximab with chemotherapy: These participants will receive encorafenib and cetuximab in the way described in the bullet above. Additionally, they will receive standard chemotherapy by IV infusion and oral treatment at home. * Chemotherapy alone: These participants will receive chemotherapy, the standard treatment for this condition, by IV infusion at the study clinics and oral treatment at home. This study is currently enrolling participants who will receive either encorafenib plus cetuximab with chemotherapy or chemotherapy alone. The study team will monitor how each participant responds to the study treatment for up to about 3 years.

Key Dates

Start date

Dec 21, 2020

Status verified

May 2026

Primary completion

Mar 1, 2025

Completion

Dec 28, 2027

Study Design

Enrollment

841 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Safety Lead-in Cohort 1
  Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
• Experimental: Safety Lead-in Cohort 2
  Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
• Experimental: Phase 3 Arm A
  Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks
• Experimental: Phase 3 Arm B
  Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
• Active Comparator: Phase 3 Arm C
  Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions)
• Experimental: Cohort 3 Arm D
  Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
• Active Comparator: Cohort 3 Arm E
  Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions)

Primary Outcome Measure

SLI: Number of Participants With Dose Limiting Toxicity (DLTs) [ Time Frame: Cycle 1 (28 days) ]

Locations (62)

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