NCT06411600

Combination Therapy for BRAF-V600E Metastatic CRCm

Bevacizumab Plus encoRAfenib-cetuximab in BRAF-V600E Mutated Metastatic Colorectal Cancer, a Phase II Study With a Safety lead-in Cohort, the BRAVE Trial

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (estimated)
• Sponsor: Vall d'Hebron Institute of Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The BRAVE is a phase II clinical trial aimed at evaluating the efficacy of the combination therapy of encorafenib, cetuximab, and bevacizumab in patients with metastatic colorectal cancer (CRC) harboring the BRAF-V600E mutation. This mutation is present in about 8-10% of CRC cases and is associated with poor prognosis and limited treatment options. The rationale behind this trial stems from preclinical studies suggesting that the overexpression and activation of vascular endothelial growth factor A (VEGFA) may contribute to resistance to BRAF inhibitors (BRAFi) in CRC. Thus, the trial hypothesizes that adding bevacizumab, an anti-angiogenic agent targeting VEGFA, to the combination of encorafenib and cetuximab may delay acquired resistance, leading to improved progression-free survival. The primary objective of the BRAVE is to evaluate the antitumor activity of the encorafenib-cetuximab-bevacizumab combination in patients who have experienced disease progression after one or two chemotherapy regimens for BRAF V600E-mutant metastatic CRC. This activity will be assessed based on the confirmed progression-free survival rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

Detailed description

Study Design: The study adopts a multicenter, open-label, phase II design. Patients with metastatic CRC harboring the BRAF-V600E mutation, who have experienced disease progression after one or two prior chemotherapy regimens, are eligible for enrollment. The treatment regimen consists of daily oral encorafenib (300 mg), biweekly intravenous cetuximab (500 mg/m2), and biweekly intravenous bevacizumab (5 mg/kg). Treatment will be administered in 28-day cycles until disease progression, unacceptable toxicity, consent withdrawal, initiation of other anticancer therapy, or death. Secondary Objectives: Secondary objectives include evaluating the safety and tolerability of the combination therapy, assessing objective response rate, time to response, duration of response, overall survival, and patient-reported outcomes. Exploratory objectives involve evaluating potential biomarkers predictive of treatment response and resistance, as well as generating functional models to assess novel drug combinations targeting resistance mechanisms.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Encorafenib	Encorafenib is administered orally at a daily dose of 300 mg, typically in the form of four 75 mg capsules taken together.
DRUG	Cetuximab	Cetuximab is administered intravenously every two weeks at a dose of 500 mg/m².
DRUG	Bevacizumab	Bevacizumab is administered intravenously every two weeks at a dose of 5 mg/kg.

Timeline

• Start date: 2024-05-17
• Primary completion: 2027-05-01
• Completion: 2029-05-01
• First posted: 2024-05-13
• Last updated: 2024-11-08

Locations

1 site across 1 country: Spain