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

NCT ID: NCT03693170

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-17
• Study Completion Date: 2023-04-27

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.

Conditions

BRAF V600E-mutant Metastatic Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 Arm

encorafenib plus binimetinib plus cetuximab

Group Type: EXPERIMENTAL

encorafenib

Intervention Type: DRUG

300 mg administered orally once daily (QD)

Binimetinib

Intervention Type: DRUG

Binimetinib 45 mg administered orally twice daily (BID)

Cetuximab

Intervention Type: 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.

Interventions

encorafenib

300 mg administered orally once daily (QD)

Intervention Type: DRUG

Binimetinib

Binimetinib 45 mg administered orally twice daily (BID)

Intervention Type: DRUG

Cetuximab

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.

Intervention Type: DRUG

Other Intervention Names

Braftovi; Mektovi; Erbitux

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

Ono Pharmaceutical Co. Ltd

INDUSTRY

Sponsor Role: collaborator

Pierre Fabre Medicament

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isabelle KLAUCK, MD

Role: STUDY_DIRECTOR

Corporate Medical&Patient/Consumer Division, Pierre Fabre Medicament

Locations

Memorial Sloan Kettering Cancer Center

New York, New York, United States

PC dba West Cancer Center

Germantown, Tennessee, United States

Krankenhaus der Barmherzigen Brüder

Vienna, , Austria

UZ Gent, Gastro-Enterology

Ghent, East Flanders, Belgium

Trial DIO, UZ Gasthuisberg

Leuven, Flemish Brabant, Belgium

Cliniques universitaires Saint-Luc

Brussels, , Belgium

ICM- VAL d 'Aurelle

Montpellier, Cedex 5, France

Hôpital Morvan CHRU de Brest Institut de cancérologie et d'hematologie

Brest, , France

AP-HM CHU Timone

Marseille, , France

Hôpital Cochin Gastroenterology

Paris, , France

Hôpital Europeen Georges Pompidou

Paris, , France

Hôpital Saint Antoine

Paris, , France

HOPITAL HAUT-LEVEQUE, Av de MAGELLAN

Pessac, , France

ICO- Site René Gauducheau

Saint-Herblain, , France

CHU TOULOUSE Rangueil

Toulouse, , France

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori

Meldola, Forlì-Cesena, Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, , Italy

Ospedale Policlinic San Martin

Genova, , Italy

Ospedale S.M. Misericordia

Perugia, , Italy

Pierre Fabre Investigative Site

Nagoya, Aichi-ken, Japan

Pierre Fabre Investigative Site

Kashiwa, Chiba, Japan

Pierre Fabre Investigative Site

Fukuoka, Fukuoka, Japan

Pierre Fabre Investigative Site

Osaka, Osaka, Japan

Pierre Fabre Investigative Site

Nagaizumi-cho, Shizuoka, Japan

Pierre Fabre Investigative Site

Koto-ku,, Tokyo, Japan

St Antonius Ziekenhuis

Utrecht, , Netherlands

Hospital Puerta de Hierro

Madrid, Madrid, Spain

Complejo Hospitalario De Navarra S Oncologia Medica

Pamplona, Navarre, Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clínic I Provincial de Barcelona

Barcelona, , Spain

Institut Català d'Oncologia (ICO L'Hospitalet)

Barcelona, , Spain

Hospital de la Santa Creu i Santa Pau

Barcelona, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Clínico Universitario de

Valencia, , Spain

Hospital Universitario y Politécnico La FE

Valencia, , Spain

Hospital Alvaro Cunqueiro

Vigo, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Torbay Hospital, Lowes Bridge

Torquay, Devon, United Kingdom

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

St James Hospital

Leeds, , United Kingdom

GI research team, OHCT, Guy's Hospital

London, , United Kingdom

GI Research Team, The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

United States; Austria; Belgium; France; Italy; Japan; Netherlands; Spain; United Kingdom

References

Van Cutsem E, Taieb J, Yaeger R, Yoshino T, Grothey A, Maiello E, Elez E, Dekervel J, Ross P, Ruiz-Casado A, Graham J, Kato T, Ruffinelli JC, Andre T, Carriere Roussel E, Klauck I, Groc M, Vedovato JC, Tabernero J. ANCHOR CRC: Results From a Single-Arm, Phase II Study of Encorafenib Plus Binimetinib and Cetuximab in Previously Untreated BRAFV600E-Mutant Metastatic Colorectal Cancer. J Clin Oncol. 2023 May 10;41(14):2628-2637. doi: 10.1200/JCO.22.01693. Epub 2023 Feb 10.

Reference Type: DERIVED

PMID: 36763936 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

W00090 GE 2 01

Identifier Type: -

Identifier Source: org_study_id