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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 16 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Safety Lead-In = Male/female ≥ 18 years old - Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally) - Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation - Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment ) - Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety Lead-in) - ECOG PS 0-1 - Adequate organ function

Exclusion Criteria

  • Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition - Active bacterial or viral infections in 2 weeks prior to starting dosing - Symptomatic brain metastases

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • Drug: Encorafenib
    75 mg capsules
    Other names:
    • Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other names:
    • Erbitux
  • Drug: Irinotecan
    Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
    Other names:
    • Campostar
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
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
  • Drug: Encorafenib
    75 mg capsules
    Other names:
    • Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other names:
    • Erbitux
  • Drug: Oxaliplatin
    Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
    Other names:
    • Eloxatin
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
Experimental
Phase 3 Arm A 		Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks
  • Drug: Encorafenib
    75 mg capsules
    Other names:
    • Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other names:
    • Erbitux
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
  • Drug: Encorafenib
    75 mg capsules
    Other names:
    • Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other names:
    • Erbitux
  • Drug: Oxaliplatin
    Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
    Other names:
    • Eloxatin
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
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)
  • Drug: Oxaliplatin
    Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
    Other names:
    • Eloxatin
  • Drug: Irinotecan
    Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
    Other names:
    • Campostar
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
  • Drug: Capecitabine
    150 mg or 500 mg Tablet
    Other names:
    • Xeloda
  • Drug: Bevacizumab
    Optional Injection for intravenous use 100 mg/vial or 400 mg/vial
    Other names:
    • Zirabev
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
  • Drug: Encorafenib
    75 mg capsules
    Other names:
    • Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other names:
    • Erbitux
  • Drug: Irinotecan
    Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
    Other names:
    • Campostar
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
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)
  • Drug: Irinotecan
    Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
    Other names:
    • Campostar
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other names:
    • Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other names:
    • Fluorouracil
  • Drug: Bevacizumab
    Optional Injection for intravenous use 100 mg/vial or 400 mg/vial
    Other names:
    • Zirabev

Recruiting Locations

Vanderbilt Oncology IDS Pharmacy
Nashville, Tennessee 37232

Vanderbilt-Ingram Cancer Center
Nashville, Tennessee 37232-6307

Vanderbilt Health Clinic at Walgreens Nippers Corner
Nashville, Tennessee 37211

Vanderbilt Health Clinic at Walgreens Donelson
Nashville, Tennessee 37214

Vanderbilt Health Clinic at Walgreens Hart Lane
Nashville, Tennessee 37216

Vanderbilt Health Clinic at Walgreens Bellevue
Nashville, Tennessee 37221

Vanderbilt Health Clinic at Walgreens Belle Meade
Nashville, Tennessee 37205

Vanderbilt Health Clinic at Walgreens Hermitage
Hermitage, Tennessee 37076

Vanderbilt Health Clinic at Walgreens Cool Springs
Franklin, Tennessee 37067

Vanderbilt Health Clinic at Walgreens La Vergne
La Vergne, Tennessee 37086

Vanderbilt Health Clinic at Walgreens Clarksville
Clarksville, Tennessee 37043

Vanderbilt Health Clinic at Walgreens Smyrna
Smyrna, Tennessee 37167

Vanderbilt Health Clinic at Walgreens Hendersonville
Hendersonville, Tennessee 37075

Vanderbilt Health Clinic at Walgreens Lebanon
Lebanon, Tennessee 37087

Vanderbilt Health Clinic at Walgreens Gallatin
Gallatin, Tennessee 37066

Vanderbilt Health Clinic at Walgreens Murfreesboro
Murfreesboro, Tennessee 37128

Henry-Joyce Cancer Center
Nashville, Tennessee 37232

More Details

Status
Recruiting
Sponsor
Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Detailed Description

The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy combination is to be used in the Phase 3 portion of the study.

Notice

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