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.
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
Drug | Synonyms | Arms |
---|
encorafenib | | 1 Arm |
Binimetinib | | 1 Arm |
Cetuximab | | 1 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
Name | Type | Description | Interventions |
---|
1 Arm | Experimental | encorafenib 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: | Active, not recruiting |
Lead Sponsor: | Pierre Fabre Medicament |
Trial Keywords
- Metastatic Colorectal Cancer
Last Updated
August 6, 2021