A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.

NCT ID: NCT05004350

Last Updated: 2025-04-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-14

Study Completion Date

2024-12-07

Brief Summary

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Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.

Detailed Description

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Conditions

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BRAF V600E Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Encorafenib and cetuximab

Safety Lead-in (SLI) phase:

28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly

Randomized (Phase II) phase:

28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly

Group Type EXPERIMENTAL

Encorafenib

Intervention Type DRUG

oral hard capsule

Cetuximab

Intervention Type DRUG

intravenous infusion

Irinotecan and cetuximab or FOLFIRI and cetuximab

Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles.

Irinotecan and cetuximab:

* irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and
* cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly

OR

FOLFIRI and cetuximab:

* irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks
* Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks
* 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and
* cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly

Group Type EXPERIMENTAL

Encorafenib

Intervention Type DRUG

oral hard capsule

Cetuximab

Intervention Type DRUG

intravenous infusion

FOLFIRI

Intervention Type DRUG

Combination of:

irinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion

Interventions

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Encorafenib

oral hard capsule

Intervention Type DRUG

Cetuximab

intravenous infusion

Intervention Type DRUG

FOLFIRI

Combination of:

irinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion

Intervention Type DRUG

Other Intervention Names

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Braftovi® PF-07263896 W0090 LGX818 ONO-7702 Erbitux® C225 Folinic acid + Fluorouracil + Irinotecan

Eligibility Criteria

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Inclusion Criteria

* Chinese male or female participant with age ≥18 years at the time of informed consent.
* Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic.
* Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma Viral Oncogene Homologue Wild Type(RAS wt) status).
* Able to provide a sufficient amount of representative tumor specimen for central prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF) mutation status and also retrospective RAS wt status and Microsatellite Instability (MSI) testing.



* Chinese male or female participant with age ≥18 years at time of informed consent.
* Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening).
* Presence of a BRAF V600E mutation in tumor tissue previously determined by a local assay at any time before screening or by the central laboratory.

Exclusion Criteria

Participants meeting any of the following criteria are not eligible to undergo molecular tumor prescreening:

* Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment
* More than two prior regimens in the metastatic setting.
* Known contraindication to receive cetuximab or irinotecan at the planned dose according to the most recent cetuximab and irinotecan local label.
* Known history of Gilbert's syndrome or is known to have any of the following genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1\*6/\*6, UGT1A1\*28/\*28 or UGT1A1\*6/\*28.
* Leptomeningeal disease.


* Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF) inhibitor, cetuximab, panitumumab or other EGFR inhibitors.
* Symptomatic brain metastasis.
* Leptomeningeal disease.
* Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 ≤1 week before the start of study intervention.
* Known history of acute or chronic pancreatitis within 6 months before the start of study intervention.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

Pierre Fabre Medicament

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shen Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

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Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Fujian Medical University - Fujian Provincial Cancer Hospital

Fuzhou, Fujian, China

Site Status

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status

The First People's Hospital of Foshan

Foshan, Guangdong, China

Site Status

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status

The Sixth Affiliated Hospital Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status

Cancer Hospital Affiliated to Shantou University Medical College

Shantou, Guangdong, China

Site Status

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Site Status

The Affiliated Hospital of Hebei University

Baoding, Hebei, China

Site Status

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status

Union Hospital Tongji medical college Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, China

Site Status

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status

The First People's Hospital of Changzhou

Changzhou, Jiangsu, China

Site Status

First Affiliated Hospital of Gannan Medical University

Ganzhou, Jiangxi, China

Site Status

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

The First Affiliated Hospital of Jinzhou Medical University

Jinzhou, Liaoning, China

Site Status

The First Hospital of China Medical University

Shenyang, Liaoning, China

Site Status

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

Site Status

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, China

Site Status

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Site Status

Shanghai East Hospital, Tongji University

Shanghai, Shanghai Municipality, China

Site Status

The Second People's Hospital of Neijiang

Neijiang, Sichuan, China

Site Status

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Site Status

The First Affiliated Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Countries

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China

Other Identifiers

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W00090GE202

Identifier Type: -

Identifier Source: org_study_id

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