Clinical Trials /

encorAfenib, biNimetinib and Cetuximab in Subjects witH previOusly Untreated BRAF-mutant ColoRectal Cancer

NCT03693170

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: encorAfenib, biNimetinib and Cetuximab in Subjects witH previOusly Untreated BRAF-mutant ColoRectal Cancer
  • Official Title: Phase II, Open-label, Single Arm, Multicenter Study of Encorafenib, Binimetinib Plus Cetuximab in Subjects With Previously Untreated BRAF V600E -Mutant Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: W00090 GE 2 01
  • NCT ID: NCT03693170

Conditions

  • BRAF V600E-mutant Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
encorafenib1 Arm
Binimetinib1 Arm
Cetuximab1 Arm

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
1 ArmExperimentalencorafenib plus binimetinib plus cetuximab
  • encorafenib
  • Binimetinib
  • Cetuximab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed Overall Response Rate (cORR) based on local tumor assessments
Time Frame:Duration of the study, approximately 25 months
Safety Issue:
Description:Assessment of tumor evaluation change from baseline

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:Percentage of subjects with complete response (CR) and partial response (PR)
Measure: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.
Safety Issue:
Description:Percentage of subjects with complete response (CR) and partial response (PR)
Measure: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.
Safety Issue:
Description:Percentage of subjects with complete response (CR) and partial response (PR)
Measure:Duration of Response (DOR) per local assessment
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description: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
Measure:Duration of Response (DOR) per central assessment
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first radiographic evidence of response review to the earliest documented PD or death due to underlying disease
Measure:Time to Response (TTR) per local review
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first dose until first documented radiographic evidence of response of CR or PR
Measure:Time to Response (TTR) per central review
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first dose until first documented radiographic evidence of response of CR or PR
Measure:Progression of Free Survival (PFS) per local review
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first dose to the earliest documented date of disease progression or death due to any cause
Measure:Progression of Free Survival (PFS) per central review
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first dose to the earliest documented date of disease progression or death due to any cause
Measure:Overall Survival (OS)
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:Time from first dose to death due to any cause
Measure:Safety through the incidence of adverse events
Time Frame:Duration of study approximately 25 months
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:Plasma concentration of encorafenib
Measure: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)
Safety Issue:
Description:Plasma concentration of binimetinib
Measure: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)
Safety Issue:
Description:Plasma concentration of cetuximab
Measure: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)
Safety Issue:
Description:Change in the Quality of Life Questionnaire for Cancer subjects.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pierre Fabre Medicament

Trial Keywords

  • Metastatic Colorectal Cancer

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