Encorafenib + Cetuximab for Colorectal Cancer

Recruiting at433 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: Pfizer

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with Stage IV colorectal cancer that has spread and has a specific gene mutation (BRAF V600E). They should not have had previous treatments for metastatic cancer, although prior adjuvant therapy is allowed if relapse occurred within 6 months. Participants need to be in good physical condition with proper organ function and no symptomatic brain metastases or recent infections.

Inclusion Criteria

I am eligible for a Phase 3 trial with no specific requirements.

My colorectal cancer is stage IV with a BRAF V600E mutation.

I have received treatment for cancer after it spread.

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Exclusion Criteria

My tumor is MSI-H/dMMR, and I can't take immune checkpoint inhibitors due to a health condition.

I have not had any bacterial or viral infections in the last 2 weeks.

I have brain metastases that are causing symptoms.

Treatment Details

Interventions

5-FU (Other)
Bevacizumab (Chemotherapy)
Capecitabine (Chemotherapy)
Cetuximab (Monoclonal Antibodies)
Encorafenib (Kinase Inhibitor)
Irinotecan (Chemotherapy)
Leucovorin (Chemotherapy)
Oxaliplatin (Chemotherapy)

Trial OverviewThe study tests encorafenib plus cetuximab alone or combined with standard chemotherapy (Oxaliplatin, Irinotecan, Bevacizumab, Leucovorin, Capecitabine, 5-FU) against chemotherapy alone. Encorafenib is taken orally daily; cetuximab is given by IV every two weeks. The goal is to compare the effectiveness of these treatments over approximately three years.

Participant Groups

7Treatment groups

Experimental Treatment

Active Control

Group I: Safety Lead-in Cohort 2Experimental Treatment5 Interventions

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

Group II: Safety Lead-in Cohort 1Experimental Treatment5 Interventions

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

Group III: Phase 3 Arm BExperimental Treatment6 Interventions

Group IV: Phase 3 Arm AExperimental Treatment2 Interventions

Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks

Group V: Cohort 3 Arm DExperimental Treatment5 Interventions

Group VI: Phase 3 Arm CActive Control6 Interventions

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)

Group VII: Cohort 3 Arm EActive Control4 Interventions

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)