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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 : Recruiting
First Posted : October 2, 2018
Last Update Posted : August 20, 2019
Sponsor:
Collaborators:
Array BioPharma
Merck KGaA, Darmstadt, Germany
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Pierre Fabre Medicament

Study Description
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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.

Condition or disease Intervention/treatment Phase
BRAF V600E-mutant Metastatic Colorectal Cancer Drug: encorafenib Drug: Binimetinib Drug: Cetuximab Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: All involved know the identity of the intervention assignment.
Primary Purpose: Treatment
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
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arms and Interventions
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Arm Intervention/treatment
Experimental: 1 Arm
encorafenib plus binimetinib plus cetuximab
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Overall Survival (OS) [ Time Frame: Duration of study approximately 25 months ]
    Time from first dose to death due to any cause

  11. Safety through the incidence of adverse events [ Time Frame: Duration of study approximately 25 months ]
  12. 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

  13. 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

  14. 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

  15. 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.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03693170


Contacts
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Contact: Karim Keddad, MD 0033534506000 contact_essais_cliniques@pierre-fabre.com

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Sponsors and Collaborators
Pierre Fabre Medicament
Array BioPharma
Merck KGaA, Darmstadt, Germany
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Karim Keddad, MD Pierre Fabre Medicament
More Information
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Responsible Party: Pierre Fabre Medicament
ClinicalTrials.gov Identifier: NCT03693170     History of Changes
Other Study ID Numbers: W00090 GE 2 01
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pierre Fabre Medicament:
Metastatic Colorectal Cancer

Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
 Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents