Bevacizumab plus encorafenib-cetuximab in BRAF-V600E mutated metastatic colorectal cancer, a phase II study with a safety lead-in cohort, the BRAVE trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vall D Hebron Institute Of Oncology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 May 2024 → ongoing

Decision date (initial)

2024-02-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Instituto de Salud Carlos III. Código: ICI21/00097 · MERCK, S.L.U. · Pierre Fabre Ibérica SA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the antitumor activity of the combination of encorafenib, cetuximab and bevacizumab in subjects who have progressed to one or two chemotherapeutic regimens for BRAF V600E-mutant mCRC.
For the safety lead-in phase only: To assess the safety and tolerability of the combination of encorafenib, cetuximab and bevacizumab.

Secondary objectives 4

1. To assess the safety and tolerability of the combination of encorafenib, cetuximab and bevacizumab.
2. To assess the activity of encorafenib, cetuximab and bevacizumab.
3. To assess the efficacy of encorafenib, cetuximab and bevacizumab.
4. To assess the patient-reported outcome (PRO) measures.

Conditions and MedDRA coding

Metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 3. Histologically- or cytologically-confirmed mCRC that is metastatic.
2. 4. 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.
3. 6. Eligible to receive cetuximab per locally approved label with regard to tumor RAS status, any time point before the enrollment in the study.
4. 7. Progression of disease after 1 or 2 prior regimens in the metastatic setting

Exclusion criteria 6

1. 5. Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Cycle 1, Day 1.
2. 6. Evidence of bleeding diathesis or clinically significant coagulopathy (in the absence of therapeutic anticoagulation).
3. 9. Tumors with microsatellite instability or mismatch repair deficiency.
4. 17. Impaired gastrointestinal (GI) function or disease that may significantly alter the absorption of encorafenib (e.g., ulcerative diseases, uncontrolled vomiting, malabsorption syndrome, small bowel resection with decreased intestinal absorption).
5. 18. Concurrent or previous other malignancy within 5 years of study entry without Sponsor approval, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy.
6. 19. History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary embolism.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Progression free survival (PFS) by local radiologist/investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1). For the safety lead-in phase only: • Incidence of dose-limiting toxicity (DLTs) during 1 month.

Secondary endpoints 4

1. • Incidence and severity of AEs graded according to the NCI CTCAE v5.0 and changes in clinical laboratory parameters, vital signs and ECGs during the treatment until 30+/-2 days after EOT. • Incidence of dose delays, dose modifications and discontinuations due to AEs.
2. • Overall Response Rate (ORR) per RECIST v1.1, defined as the number of patients achieving an overall best response of complete response (CR) or partial response (PR) divided by the total number of patients. • Time to response, defined as the time from first dose to first radiographic evidence of response. • Duration of Response (DOR), defined as the time from first radiographic evidence of response to the earliest documented disease progression or death due to underlying disease.
3. • Overall Survival (OS), defined as the time from first dose to death due to any cause.
4. • Change in PRO as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30) and Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vall D Hebron Institute Of Oncology

Sponsor organisation

Vall D Hebron Institute Of Oncology

Address

Calle Natzaret 115

City

Barcelona

Postcode

08035

Country

Spain

Scientific contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

Susana Muñoz

Public contact point

Organisation

Vall D Hebron Institute Of Oncology

Contact name

Susana Muñoz

Third parties 1

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications