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

NCT02928224

Last updated date
Study Location
Mayo Clinic Hospital
Phoenix, Arizona, 85054, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
BRAF V600E-mutant Metastatic Colorectal Cancer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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

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


- 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

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  17. Leuven, Flemish Brabant
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  43. Pamplona, Navarre
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ALL GENDERS
18 Years+
years
MULTIPLE SITES
BRAF V600E-mutant Metastatic Colorectal CancerStudy 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
NCT02928224
  1. Phoenix, Arizona
  2. Corona, California
  3. Duarte, California
  4. Fountain Valley, California
  5. Fullerton, California
  6. Los Angeles, California
  7. Riverside, California
  8. Aurora, Colorado
  9. New Haven, Connecticut
  10. Washington, District of Columbia
  11. Fort Lauderdale, Florida
  12. Jacksonville, Florida
  13. Miami, Florida
  14. Atlanta, Georgia
  15. Chicago, Illinois
  16. Peoria, Illinois
  17. Urbana, Illinois
  18. Indianapolis, Indiana
  19. New Albany, Indiana
  20. Iowa City, Iowa
  21. Westwood, Kansas
  22. New Orleans, Louisiana
  23. Baltimore, Maryland
  24. Boston, Massachusetts
  25. Boston, Massachusetts
  26. Ypsilanti, Michigan
  27. Rochester, Minnesota
  28. Saint Louis, Missouri
  29. Saint Louis, Missouri
  30. Lebanon, New Hampshire
  31. Albuquerque, New Mexico
  32. New York, New York
  33. Canton, Ohio
  34. Cleveland, Ohio
  35. Toledo, Ohio
  36. Portland, Oregon
  37. Danville, Pennsylvania
  38. Pittsburgh, Pennsylvania
  39. Nashville, Tennessee
  40. Houston, Texas
  41. Temple, Texas
  42. Seattle, Washington
  43. Spokane, Washington
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  45. Darlinghurst, New South Wales
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Advanced Information
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE BRAF V600E-mutant Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: Encorafenib
    Orally, once daily.
  • Drug: Binimetinib
    Orally, twice daily.
  • Drug: Cetuximab
    Standard of care.
  • Drug: Irinotecan
    Standard of care.
  • Drug: Folinic Acid
    Standard of care.
    Other Name: FA
  • Drug: 5-Fluorouracil
    Standard of care.
    Other Name: 5-FU
Study Arms  ICMJE
  • Experimental: Safety Lead-in, Triplet Arm
    Encorafenib + binimetinib + cetuximab.
    Interventions:
    • Drug: Encorafenib
    • Drug: Binimetinib
    • Drug: Cetuximab
  • Experimental: Doublet Arm
    Encorafenib + cetuximab.
    Interventions:
    • Drug: Encorafenib
    • Drug: Cetuximab
  • Active Comparator: Control Arm
    Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab.
    Interventions:
    • Drug: Cetuximab
    • Drug: Irinotecan
    • Drug: Folinic Acid
    • Drug: 5-Fluorouracil
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 19, 2020)
702
Original Estimated Enrollment  ICMJE
 (submitted: October 6, 2016)
645
Estimated Study Completion Date  ICMJE August 2020
Actual Primary Completion Date February 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   Czechia,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Poland,   Russian Federation,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02928224
Other Study ID Numbers  ICMJE ARRAY-818-302
2015-005805-35 ( EudraCT Number )
C4221009 ( Other Identifier: Pfizer )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE
  • Merck KGaA, Darmstadt, Germany
  • Pierre Fabre Medicament
  • Ono Pharmaceutical Co. Ltd
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date July 2020

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