BRAF V600E-mutant Metastatic Colorectal Cancer Clinical Trial
— ANCHOR-CRCOfficial 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
Verified date | January 2024 |
Source | Pierre Fabre Medicament |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 95 |
Est. completion date | April 27, 2023 |
Est. primary completion date | June 29, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Austria | Krankenhaus der Barmherzigen Brüder | Wien | |
Belgium | Cliniques universitaires Saint-Luc | Brussels | |
Belgium | UZ Gent, Gastro-Enterology | Gent | East Flanders |
Belgium | Trial DIO, UZ Gasthuisberg | Leuven | Flemish Brabant |
France | Hôpital Morvan CHRU de Brest Institut de cancérologie et d'hematologie | Brest | |
France | AP-HM CHU Timone | Marseille | |
France | ICM- VAL d 'Aurelle | Montpellier | Cedex 5 |
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 | |
Italy | Fondazione del Piemonte per l'Oncologia IRCC Candiolo | Candiolo | |
Italy | Ospedale Policlinic San Martin | Genova | |
Italy | Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori | Meldola | Forlì-Cesena |
Italy | Ospedale S.M. Misericordia | Perugia | |
Italy | IRCCS Ospedale Casa Sollievo della Sofferenza | San Giovanni Rotondo | Foggia |
Japan | Pierre Fabre Investigative Site | Fukuoka-shi | Fukuoka |
Japan | Pierre Fabre Investigative Site | Kashiwa | Chiba |
Japan | Pierre Fabre Investigative Site | Koto-ku, | Tokyo |
Japan | Pierre Fabre Investigative Site | Nagaizumi-cho | Shizuoka |
Japan | Pierre Fabre Investigative Site | Nagoya | Aichi |
Japan | Pierre Fabre Investigative Site | Osaka-shi | Osaka |
Netherlands | St Antonius Ziekenhuis | Utrecht | |
Spain | Hospital Clínic I Provincial de Barcelona | Barcelona | |
Spain | Hospital de la Santa Creu i Santa Pau | Barcelona | |
Spain | Hospital Vall d'Hebron | Barcelona | |
Spain | Institut Català d'Oncologia (ICO L'Hospitalet) | Barcelona | |
Spain | Hospital General Universitario Gregorio Marañón | Madrid | |
Spain | Hospital Puerta de Hierro | Madrid | Community Of Madrid |
Spain | Hospital Universitario HM Sanchinarro | Madrid | |
Spain | Complejo Hospitalario De Navarra S Oncologia Medica | Pamplona | Navarre |
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 | |
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 | The Royal Marsden NHS Foundation Trust | Sutton | Surrey |
United Kingdom | Torbay Hospital, Lowes Bridge | Torquay | Devon |
United States | PC dba West Cancer Center | Germantown | Tennessee |
United States | Memorial Sloan Kettering Cancer Center | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Pierre Fabre Medicament | Merck KGaA, Darmstadt, Germany, Ono Pharmaceutical Co. Ltd, Pfizer |
United States, Austria, Belgium, France, Italy, Japan, Netherlands, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Confirmed Overall Response Rate (cORR) Based on Local Tumor Assessments | 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. |
From initiation of treatment to disease progression up to a maximum of 17.6 months. | |
Secondary | Confirmed Overall Response Rate (cORR) Based on Central Tumor Assessment | 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. |
From initiation of treatment to disease progression up to a maximum of 17.6 months | |
Secondary | Overall Response Rate (ORR) Based on Local Tumor Assessments | 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. |
From initiation of treatment to disease progression up to a maximum of 17.6 months | |
Secondary | Overall Response Rate (ORR) Based on Central Tumor Assessments | 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. |
From initiation of treatment to disease progression up to a maximum of 17.6 months | |
Secondary | Duration of Response (DOR) Per Local Assessment | Time from first radiographic evidence of response based on local radiologist/investigator review to the earliest documented PD or death due to underlying disease | From first radiographic evidence of response to disease progression up to a maximum of 17.6 months | |
Secondary | Duration of Response (DOR) Per Central Assessment | Time from first radiographic evidence of response based on central review to the earliest documented PD or death due to underlying disease | From first radiographic evidence of response to disease progression up to a maximum of 17.6 months | |
Secondary | Time to Response (TTR) Per Local Review | 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 | From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months | |
Secondary | Time to Response (TTR) Per Central Review | 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 | From initiation of treatment to the first radiographic evidence of response up to a maximum of 17.6 months | |
Secondary | Progression-Free Survival (PFS) Per Local Review | Time from first dose to the earliest documented date of disease progression based on local radiologist/investigator review or death due to any cause | From initiation of treatment to disease progression or death up to a maximum of 17.6 months | |
Secondary | Progression of Free Survival (PFS) Per Central Review | Time from first dose to the earliest documented date of disease progression based on central review or death due to any cause | From initiation of treatment to disease progression or death up to a maximum of 17.6 months | |
Secondary | Overall Survival (OS) | Time from first dose to death due to any cause | From initiation of treatment to death up to a maximum of 17.6 months | |
Secondary | Plasma Concentration of Encorafenib | 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) | |
Secondary | Plasma Concentration of Binimetinib | 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) | |
Secondary | Plasma Concentration of Cetuximab | 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) | |
Secondary | Change From Baseline in EORTC QLQ-C30 Over Time | 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. |
From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months | |
Secondary | Change From Baseline in EQ-5D-5L Over Time | 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. | From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months | |
Secondary | PGIC Scores Over Time | 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." | From Cycle 1 Day 1 (C1D1) Visit to the 30-day Safety Follow-up Visit up to a maximum of 17.6 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02928224 -
Study of Encorafenib + Cetuximab Plus or Minus Binimetinib vs. Irinotecan/Cetuximab or Infusional 5-Fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab With a Safety Lead-in of Encorafenib + Binimetinib + Cetuximab in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer
|
Phase 3 |