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

Sponsor

Pierre Fabre Medicament (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03693170

Collaborator

Pfizer (Industry), Merck KGaA, Darmstadt, Germany (Industry), Ono Pharmaceutical Co. Ltd (Industry)

Enrollment

Locations

Arm

35.4

Anticipated Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated Enrollment :

95 participants

Allocation:

N/A

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 :

Jan 17, 2019

Anticipated Primary Completion Date :

Dec 29, 2021

Anticipated Study Completion Date :

Dec 29, 2021

Arms and Interventions

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

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

Primary Outcome Measures

Confirmed Overall Response Rate (cORR) based on local tumor assessments [Duration of the study, approximately 25 months]
Assessment of tumor evaluation change from baseline

Secondary Outcome Measures

Confirmed Overall Response Rate (cORR) based on central tumor assessment [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 [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 [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 [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 [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 [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 [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 [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 [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) [Duration of study approximately 25 months]
Time from first dose to death due to any cause
Safety through the incidence of adverse events [Duration of study approximately 25 months]
Plasma concentration of encorafenib [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 [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 [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 [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
2	PC dba West Cancer Center	Germantown	Tennessee	United States	38138
3	Krankenhaus der Barmherzigen Brüder	Wien		Austria	1020
4	UZ Gent, Gastro-Enterology	Gent	East Flanders	Belgium	9000
5	Trial DIO, UZ Gasthuisberg	Leuven	Flemish Brabant	Belgium	3000
6	Cliniques universitaires Saint-Luc	Brussels		Belgium	1200
7	ICM- VAL d 'Aurelle	Montpellier	Cedex 5	France	34298
8	Hôpital Morvan CHRU de Brest Institut de cancérologie et d'hematologie	Brest		France	29200
9	AP-HM CHU Timone	Marseille		France	13005
10	Hôpital Cochin Gastroenterology	Paris		France	75014
11	Hôpital Europeen Georges Pompidou	Paris		France	75015
12	Hôpital Saint Antoine	Paris		France	75571
13	HOPITAL HAUT-LEVEQUE, Av de MAGELLAN	Pessac		France	33604
14	ICO- Site René Gauducheau	Saint-Herblain		France	44805
15	CHU TOULOUSE Rangueil	Toulouse		France
16	IRCCS Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia	Italy	71013
17	Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori	Meldola	Forlì-Cesena	Italy	47014
18	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo		Italy	10060
19	Ospedale Policlinic San Martin	Genova		Italy	16132
20	Ospedale S.M. Misericordia	Perugia		Italy	06129
21	Pierre Fabre Investigative Site	Nagoya	Aichi	Japan	464-8681
22	Pierre Fabre Investigative Site	Kashiwa	Chiba	Japan	277-8577
23	Pierre Fabre Investigative Site	Fukuoka-shi	Fukuoka	Japan	811-1395
24	Pierre Fabre Investigative Site	Osaka-shi	Osaka	Japan	540-0006
25	Pierre Fabre Investigative Site	Nagaizumi-cho	Shizuoka	Japan	411-8777
26	Pierre Fabre Investigative Site	Koto-ku,	Tokyo	Japan	135-8550
27	St Antonius Ziekenhuis	Utrecht		Netherlands	3543 AZ
28	Hospital Puerta de Hierro	Madrid	Community Of Madrid	Spain	28222
29	Complejo Hospitalario De Navarra S Oncologia Medica	Pamplona	Navarre	Spain	31008
30	Hospital Vall d'Hebron	Barcelona		Spain	08035
31	Hospital Clínic I Provincial de Barcelona	Barcelona		Spain	08036
32	Institut Català d'Oncologia (ICO L'Hospitalet)	Barcelona		Spain	08908
33	Hospital de la Santa Creu i Santa Pau	Barcelona		Spain
34	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28009
35	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
36	Hospital Clínico Universitario de	Valencia		Spain	46010
37	Hospital Universitario y Politécnico La FE	Valencia		Spain	46026
38	Hospital Alvaro Cunqueiro	Vigo		Spain	36312
39	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
40	Torbay Hospital, Lowes Bridge	Torquay	Devon	United Kingdom	TQ2 7AA
41	The Royal Marsden NHS Foundation Trust	Sutton	Surrey	United Kingdom	SM2 5PT
42	Beatson West of Scotland Cancer Centre	Glasgow		United Kingdom	G12 0YN
43	St James Hospital	Leeds		United Kingdom	LS9 7TF
44	GI research team, OHCT, Guy's Hospital	London		United Kingdom	SE1 9RT
45	GI Research Team, The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX

Sponsors and Collaborators

Pierre Fabre Medicament
Pfizer
Merck KGaA, Darmstadt, Germany
Ono Pharmaceutical Co. Ltd

Investigators

Study Director: Isabelle KLAUCK, MD, Corporate Medical&Patient/Consumer Division, Pierre Fabre Medicament

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Pierre Fabre Medicament

ClinicalTrials.gov Identifier:

NCT03693170

Other Study ID Numbers:

W00090 GE 2 01

First Posted:

Oct 2, 2018

Last Update Posted:

Aug 6, 2021

Last Verified:

Aug 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Pierre Fabre Medicament

Metastatic Colorectal Cancer

Additional relevant MeSH terms:

Colorectal Neoplasms

Cetuximab

Study Results

No Results Posted as of Aug 6, 2021