BRAF V600E-mutant Colorectal Cancer Study of Encorafenib Taken With Cetuximab Plus or Minus Chemotherapy (BREAKWATER)

NCT04607421

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Neoplasms
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
16 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Safety Lead-In = Male/female ≥ 18 years old

- Phase 3: Male/female ≥ 16 years old

- Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation

- Prior systemic treatment in metastatic setting

- SLI: 0-1 regimens

- Phase 3: None

- Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment

- Measurable disease (Phase 3)/ Measurable or evaluable disease (Safety Lead-in)

- ECOG PS 0-1

- Adequate organ function

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Tumors that are locally confirmed 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

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Advanced Information
Descriptive Information
Brief Title  ICMJE BRAF V600E-mutant Colorectal Cancer Study of Encorafenib Taken With Cetuximab Plus or Minus Chemotherapy (BREAKWATER)
Official Title  ICMJE AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE 3 STUDY OF FIRST-LINE ENCORAFENIB PLUS CETUXIMAB WITH OR WITHOUT CHEMOTHERAPY VERSUS STANDARD OF CARE THERAPY WITH A SAFETY LEAD-IN OF ENCORAFENIB AND CETUXIMAB PLUS CHEMOTHERAPY IN PARTICIPANTS WITH METASTATIC BRAF V600E-MUTANT COLORECTAL CANCER
Brief Summary 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: Encorafenib
    75 mg capsules
    Other Name: Braftovi, PF-07263896, LGX818, ONO-7702
  • Drug: Cetuximab
    Injection for intravenous use 100 mg/vial, 200 mg/vial, or 500 mg/vial
    Other Name: Erbitux
  • Drug: Oxaliplatin
    Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
    Other Name: Eloxatin
  • Drug: Irinotecan
    Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial
    Other Name: Campostar
  • Drug: Leucovorin
    Injection 50 mg/vial, 100 mg/vial, 200 mg/vial, or 350 mg/vial
    Other Name: Wellcovorin, Fusilev, Khapzory
  • Drug: 5-FU
    Injection for intravenous use 250 mg/vial, 500 mg/vial, or 1000 mg/vial
    Other Name: Fluorouracil
  • Drug: Capecitabine
    150 mg or 500 mg Tablet
    Other Name: Xeloda
  • Drug: Bevacizumab
    Optional Injection for intravenous use 100 mg/vial or 400 mg/vial
    Other Name: Zirabev
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
    • Drug: Irinotecan
    • Drug: Leucovorin
    • Drug: 5-FU
  • 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
    Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
    • Drug: Oxaliplatin
    • Drug: Leucovorin
    • Drug: 5-FU
  • Experimental: Phase 3 Arm A
    Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks
    Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
  • Experimental: Phase 3 Arm B
    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 -OR- 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
    Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
    • Drug: Oxaliplatin
    • Drug: Irinotecan
    • Drug: Leucovorin
    • Drug: 5-FU
  • 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-

    Every two weeks:

    Irinotecan 180 mg/m2 (90-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- 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)

    Interventions:
    • Drug: Oxaliplatin
    • Drug: Irinotecan
    • Drug: Leucovorin
    • Drug: 5-FU
    • Drug: Capecitabine
    • Drug: Bevacizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: October 22, 2020)
930
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 15, 2026
Estimated Primary Completion Date September 16, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  • Tumors that are locally confirmed 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04607421
Other Study ID Numbers  ICMJE C4221015
2020-001288-99 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:Yes
Plan Description: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/d….
URL:https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d…
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE
  • Ono Pharmaceutical Co. Ltd
  • Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP