Combination Therapy for BRAF-V600E Metastatic CRCm
ConditionMetastatic Colorectal Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVall d'Hebron Institute of Oncology
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Provision of signed and dated informed consent form.
Age ≥18 years at time of informed consent.
Histologically- or cytologically-confirmed mCRC that is metastatic.
Presence of BRAF V600E mutation in tumor tissue previously determined according to the guidelines of each center, any time point before the enrollment in the study.
Disqualifiers
Treatment with another investigational drug or participation in another investigational study at enrolment or within 30 days prior to enrolment.
Patient unable to comply with the study protocol owing to psychological, social (lack of social support or social exclusion) or geographical reasons.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
Prior history of hypertensive crisis or hypertensive encephalopathy.
Trial design
Design model
Parallel
Treatments tested in this trial
Encorafenib
DrugEncorafenib is administered orally at a daily dose of 300 mg, typically in the form of four 75 mg capsules taken together.
Cetuximab
DrugCetuximab is administered intravenously every two weeks at a dose of 500 mg/m².
Bevacizumab
DrugBevacizumab is administered intravenously every two weeks at a dose of 5 mg/kg.
Treatment groups
94 Participants
are divided into 2 treatment groupsGroup A: Experimental armExperimental treatment 3 interventions
Group B: Control armActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Progression-Free Survival (PFS)
PFS will be evaluated by local radiologist/investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). It refers to the duration from the start of treatment until disease progression or death due to any cause.
Time frame
Until disease progression, typically within a follow-up period of approximately 5 years.Secondary outcomes
1
Objective Response Rate (ORR)
ORR will be determined as the proportion of patients achieving a complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.
Time frame
Throughout the study duration, that it will take 5 years2
Duration of Response (DOR)
DOR is defined as the duration from the first radiographic evidence of response to the earliest documented disease progression or death due to underlying disease.
Time frame
Until disease progression, typically within a follow-up period of approximately 5 years.3
Disease Control Rate (DCR)
The proportion of patients who achieve a complete response, partial response, or stable disease as the best overall response to treatment.
Time frame
Throughout the study duration, that it will take 5 years4
Electrocardiogram (ECG) Changes
This outcome measure assesses changes in electrocardiogram (ECG) parameters in participants receiving treatment with encorafenib in combination with cetuximab and bevacizumab, as well as up to 30 ± 2 days after the last dose. ECG recordings will be analyzed for parameters such as QT interval duration, presence of arrhythmias, and other relevant ECG changes.
Time frame
During treatment (until disease progression) and up to 30 ± 2 days after the last dose.Sponsors and contacts
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Source ClinicalTrials.gov