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

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

September 17, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

June 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

Current Secondary Outcome Measures ^ICMJE

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.

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

Phase 2

Study Design ^ICMJE

Allocation:
Intervention Model: Single Group Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:All involved know the identity of the intervention assignment.
Primary Purpose: Treatment

Condition ^ICMJE

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

Experimental: 1 Arm
encorafenib plus binimetinib plus cetuximab

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

October 2020

Estimated Primary Completion Date

June 2020 (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

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

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

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Pierre Fabre Medicament

Collaborators ^ICMJE

Investigators ^ICMJE

Study Director: Karim Keddad, MD Pierre Fabre Medicament

PRS Account

Verification Date

October 2018

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

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