Combination Therapy for BRAF-V600E Metastatic CRCm

Sponsor
Vall d'Hebron Institute of Oncology
Study ID
NCT06411600
Phase
PHASE2
Status
Recruiting
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Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

First listed
May 13, 2024
Start date
May 17, 2024
Status verified
Nov 2024
Primary completion
May 1, 2027
Completion
May 1, 2029

Study Design

Enrollment
94 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Experimental arm
    The experimental arm in the BRAVE protocol involves the administration of a combination therapy consisting of encorafenib, cetuximab, and bevacizumab. This arm is designed to evaluate the efficacy and safety of this combination in patients with metastatic colorectal cancer harboring the BRAF-V600E mutation who have experienced disease progression after one or two prior chemotherapy regimens. The primary objective is to assess the antitumor activity of the combination therapy, with secondary objectives including safety and tolerability assessments, as well as evaluations of progression-free survival, overall survival, and patient-reported outcomes.
  • Active Comparator: Control arm
    The control arm in the BRAVE protocol involves standard-of-care treatment, which may include various chemotherapy regimens or targeted therapies typically used for metastatic colorectal cancer. In this arm, patients receive the standard treatment without the addition of encorafenib, cetuximab, or bevacizumab. The purpose of the control arm is to provide a reference point for comparing the efficacy and safety of the experimental combination therapy. Patients in this arm may also undergo similar assessments for tumor response, survival outcomes, and adverse events to facilitate comparison with the experimental arm.

Primary Outcome Measure

Progression-Free Survival (PFS) [ Time Frame: Until disease progression, typically within a follow-up period of approximately 5 years. ]

Central Contacts

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