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Trial record 1 of 1 for:    NCT03693170
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Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer (ANCHOR-CRC)

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ClinicalTrials.gov Identifier: NCT03693170
Recruitment Status : Active, not recruiting
First Posted : October 2, 2018
Last Update Posted : March 19, 2021
Sponsor:
Collaborators:
Pfizer
Merck KGaA, Darmstadt, Germany
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Pierre Fabre Medicament

Tracking Information
First Submitted Date  ICMJE September 17, 2018
First Posted Date  ICMJE October 2, 2018
Last Update Posted Date March 19, 2021
Actual Study Start Date  ICMJE January 17, 2019
Estimated Primary Completion Date December 29, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
Confirmed Overall Response Rate (cORR) based on local tumor assessments [ Time Frame: Duration of the study, approximately 25 months ]
Assessment of tumor evaluation change from baseline
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • Confirmed Overall Response Rate (cORR) based on central tumor assessment [ Time Frame: globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks. ]
    Percentage of subjects with complete response (CR) and partial response (PR)
  • Overall response (ORR) based on local tumor assessments [ Time Frame: Globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks. ]
    Percentage of subjects with complete response (CR) and partial response (PR)
  • Overall response (ORR) based on central tumor assessments [ Time Frame: Globally assessed by subject based on tumor evaluations every 6 weeks for the first 12 weeks and then every 8 weeks. ]
    Percentage of subjects with complete response (CR) and partial response (PR)
  • Duration of Response (DOR) per local assessment [ Time Frame: Duration of study approximately 25 months ]
    Time from first radiographic evidence of response assessed based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease
  • Duration of Response (DOR) per central assessment [ Time Frame: Duration of study approximately 25 months ]
    Time from first radiographic evidence of response review to the earliest documented PD or death due to underlying disease
  • Time to Response (TTR) per local review [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose until first documented radiographic evidence of response of CR or PR
  • Time to Response (TTR) per central review [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose until first documented radiographic evidence of response of CR or PR
  • Progression of Free Survival (PFS) per local review [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose to the earliest documented date of disease progression or death due to any cause
  • Progression of Free Survival (PFS) per central review [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose to the earliest documented date of disease progression or death due to any cause
  • Overall Survival (OS) [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose to death due to any cause
  • Safety through the incidence of adverse events [ Time Frame: Duration of study approximately 25 months ]
  • Plasma concentration of encorafenib [ Time Frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days) ]
    Plasma concentration of encorafenib
  • Plasma concentration of binimetinib [ Time Frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days) ]
    Plasma concentration of binimetinib
  • Plasma concentration of cetuximab [ Time Frame: 2 hours and 6 hours after dose on Day 1 cycle 1; Predose and 2 hours post dose on Day 1 cycle 2 (cycle length = 28 days) ]
    Plasma concentration of cetuximab
  • Comparison of Quality of Life from Baseline to end of the study [ Time Frame: At screening, at Cycle 1 Day 1 and at the end of the study (each cycle is 28 days) ]
    Change in the Quality of Life Questionnaire for Cancer subjects.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer
Official Title  ICMJE Phase II, Open-label, Single Arm, Multicenter Study of Encorafenib, Binimetinib Plus Cetuximab in Subjects With Previously Untreated BRAF V600E -Mutant Metastatic Colorectal Cancer
Brief Summary The purpose of this study is to evaluate the efficacy and safety of the combination of study drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic colorectal cancer and have not received any prior treatment for their metastatic disease.
Detailed Description The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. The preclinical results and preliminary clinical data together justify the evaluation of this triple combination in the first-line setting of this population. The primary objective of the study is to evaluate the antitumor activity of the combination of encorafenib, binimetinib and cetuximab by assessing the overall response rate in adult subjects with previously untreated BRAFV600E-mutant metastatic colorectal cancer. It will also assess the effect of the triple combination on the duration of response, time to response, progression-free survival and overall survival and assess the effect on quality of life. It will also characterize the safety and tolerability of the triple combination as well as describe the pharmacokinetics (PK) of encorafenib, binimetinib, and cetuximab.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:
All involved know the identity of the intervention assignment.
Primary Purpose: Treatment
Condition  ICMJE BRAF V600E-mutant Metastatic Colorectal Cancer
Intervention  ICMJE
  • Drug: encorafenib
    Once daily, orally
  • Drug: Binimetinib
    Twice daily, orally
  • Drug: Cetuximab
    Standard of care for the 28 first weeks and then every 2 weeks
Study Arms  ICMJE Experimental: 1 Arm
encorafenib plus binimetinib plus cetuximab
Interventions:
  • Drug: encorafenib
  • Drug: Binimetinib
  • Drug: Cetuximab
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 Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 3, 2020)
95
Original Estimated Enrollment  ICMJE
 (submitted: October 1, 2018)
90
Estimated Study Completion Date  ICMJE December 29, 2021
Estimated Primary Completion Date December 29, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female ≥ 18 years of age
  • Histologically or cytologically confirmed CRC that is metastatic
  • Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening and confirmed by central laboratory
  • Evidence of measurable disease as per RECIST, v1.1
  • Subject able to receive cetuximab as per approved label with regards to RAS status
  • ECOG Status 0 or 1
  • Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes as per protocol
  • Subject able to take oral medications

Exclusion Criteria:

  • Prior systemic therapy for metastatic disease
  • Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR inhibitors
  • Symptomatic brain metastasis or Leptomeningeal disease
  • History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors for RVO
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first dose.
  • Impaired cardiovascular function or clinically significant cardiovascular diseases: history of myocardial infarction or coronary disorders within 6 months prior to start of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or current clinically significant arrhythmia and/or conduction disorder within 6 months prior to study treatment start
  • History of thromboembolic or cerebrovascular events within 6 months prior to start of study treatment
  • Concurrent neuromuscular disorder that is associated with potential elevation of Creatine Kinase
  • Known contraindication to cetuximab administration as per SPC/approved label
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 Austria,   Belgium,   France,   Italy,   Japan,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03693170
Other Study ID Numbers  ICMJE W00090 GE 2 01
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 Not Provided
Responsible Party Pierre Fabre Medicament
Study Sponsor  ICMJE Pierre Fabre Medicament
Collaborators  ICMJE
  • Pfizer
  • Merck KGaA, Darmstadt, Germany
  • Ono Pharmaceutical Co. Ltd
Investigators  ICMJE
Study Director: Karim Keddad, MD Pierre Fabre Medicament
PRS Account Pierre Fabre Medicament
Verification Date March 2021

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