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Completed

NCT Number: NCT03693170

Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer

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.

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Key information

Conditions

BRAF V600E-mutant Metastatic Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Krankenhaus der Barmherzigen Brüder, Vienna, Austria

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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
  • Evidence of measurable disease as per RECIST, v1.1
  • Subject able to receive cetuximab as per approved label with regards to RAS status
  • Eastern Cooperative Oncology Group Status (ECOG) 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

Treatment and study plan

Encorafenib

Drug

300 mg administered orally once daily (QD)

Other names: Braftovi

Binimetinib

Drug

Binimetinib 45 mg administered orally twice daily (BID)

Other names: Mektovi

Cetuximab

Drug

Standard of care for the 28 first weeks(*) and then every 2 weeks (**) :

(*) 400 mg/m2 administered as a 120-min infusion on Cycle 1 Day 1, followed by 250 mg/m2 administered as a 60-min infusion once weekly (QW) for the first 28 weeks. (**) 500 mg/m2 administered as a 120-min infusion twice weekly (Q2W) from Week 29 (Cycle 8 Day 1) onward.

Following implementation of an Urgent Safety Measure on 26 Mar 2020 due to the outbreak of COVID-19 pandemic, cetuximab infusions could be administered Q2W regardless of the cycle number, after investigator's evaluation of the benefit/risk ratio for the subject, with regards to COVID-19 pandemic.

Other names: Erbitux

Primary outcomes

  1. Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments

    Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months.

    The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

    Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

Secondary outcomes

  1. Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment

    Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months

    The confirmed overall response rate (cORR) is the percentage of confirmed responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

    Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

  2. Overall Response Rate (ORR) Based on Local Tumor Assessments

    Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months

    The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by local radiologist/investigator review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

    Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

  3. Overall Response Rate (ORR) Based on Central Tumor Assessments

    Time frame: From initiation of treatment to disease progression up to a maximum of 17.6 months

    The overall response rate (ORR) is the percentage of responses, defined as complete response (CR) or partial response (PR), as assessed by central radiologist review based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

    Complete Response (CR): Disappearance of all target lesions; Partiel response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Overall Response (OR) = CR + PR.

  4. Duration of Response (DOR) Per Local Assessment

    Time frame: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months

    Time from first radiographic evidence of response 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: From first radiographic evidence of response to disease progression up to a maximum of 17.6 months

    Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease

  6. Time to Response (TTR) Per Local Review

    Time frame: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months

    The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per local review

  7. Time to Response (TTR) Per Central Review

    Time frame: From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months

    The TTR is defined as the time from the first dose until the first documented radiographic evidence of response of CR or PR per central review

  8. Progression-Free Survival (PFS) Per Local Review

    Time frame: From initiation of treatment to disease progression or death up to a maximum of 17.6 months

    Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause

  9. Progression of Free Survival (PFS) Per Central Review

    Time frame: From initiation of treatment to disease progression or death up to a maximum of 17.6 months

    Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause

  10. Overall Survival (OS)

    Time frame: From initiation of treatment to death up to a maximum of 17.6 months

    Time from first dose to death due to any cause

  11. Change From Baseline in EORTC QLQ-C30 Over Time

    Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for cancer subjects (EORTC QLQ-C30) includes a global health status/QoL. The scale ranges in score from 0 to 100, higher score on the global health status/QoL scale indicate higher QoL.

    Changes from baseline in EORTC QLQ-C30 global health status/quality of life (QoL) over time are presented in this record.

  12. Change From Baseline in EQ-5D-5L Over Time

    Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

    The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L VAS records the patient's self-rated health on a vertical visual analogue scale numbered from 0 ("The worst health you can imagine") to 100 ("The best health you can imagine"). Changes from baseline in EQ-5D-5L VAS over time are presented in this record.

  13. PGIC Scores Over Time

    Time frame: From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months

    The Patient Global Impression of Change (PGIC) is a measure of patients' perceptions of change in their symptoms over time. For this assessment, subjects answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse."

Sponsors and collaborators

Lead sponsor

Pierre Fabre Medicament

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany
  • Pfizer

Registry information

Official study 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

Acronym: ANCHOR-CRC

Important dates

Study start
2019
Primary completion
2020
Study completion
2023
First posted
Oct 2, 2018
Registry last updated
Jul 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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