The BREAKWATER Study
Research type
Research Study
Full title
AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE 3 STUDY OF FIRST LINE ENCORAFENIB PLUS CETUXIMAB WITH OR WITHOUT CHEMOTHERAPY VERSUS STANDARD OF CARE THERAPY WITH A SAFETY LEAD-IN OF ENCORAFENIB AND CETUXIMAB PLUS CHEMOTHERAPY IN PARTICIPANTS WITH METASTATIC BRAF V600E MUTANT COLORECTAL CANCER
IRAS ID
283893
Contact name
Harpreet Wasan
Contact email
Sponsor organisation
Pfizer Inc.
Eudract number
2020-001288-99
Duration of Study in the UK
5 years, 8 months, 1 days
Research summary
Metastatic colorectal cancer (mCRC) continues to be a life-threatening condition. Globally, colorectal cancer is the third most diagnosed cancer in males and the second in females, with 1.8 million new cases and almost 861,000 deaths in 2018, according to the World Health Organisation.
BRAF proto-oncogene is a human gene that makes a protein called BRAF, which is involved in sending signals in cells and in cell growth. BRAF mutations (a change in the BRAF gene) occur in approximately 10% to 15% of CRC and are associated with a poor prognosis. Currently, there are no approved medicines indicated specifically for the first treatment of patients with this BRAF V600E-mutant mCRC. Analyses of studies in previously untreated patients with mCRC have shown that current standard therapies have all similar efficacy in patients with BRAF-mutant tumours.
The purpose of this study is to evaluate whether the study drugs, encorafenib and cetuximab (EC), with or without chemotherapy, can improve clinical outcomes relative to current standard chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC.
EC in combination have been approved by health authorities for the treatment of adult patients with BRAF V600E-mutant mCRC, after prior treatments, but not for patients who have received no prior treatments.In this study, the participants will undergo a series of procedures such as scans, collection of blood samples, ECGs, biopsies, pregnancy tests (if appropriate), physical examinations and questions to monitor their progress and health.
The duration of the study for each patient will depend on the length of the treatment period and follow up.
The study includes a Safety Lead-In (SLI) to be conducted at a selected number of countries, including the UK, before the Phase 3 portion of the study.
The SLI will evaluate the safety/tolerability of EC, how it is absorbed by the body and how it is processed by the body, in combination with current chemotherapy treatments. The results of the SLI will indicate which chemotherapy treatment, if any, will be used in combination within the Phase 3 portion of the study.
In the Phase 3 portion, participants will be randomised to receive EC only (Arm A), EC + chemotherapy (Arm B, depending on results of SLI phase), or standard of care chemotherapy (Control Arm).
There will be about 60 people taking part in the SLI, and 870 people in the phase 3 portion. The SLI study is being done at about 40 different study sites in approximately 11 countries.
This is an open label study. The study is being sponsored by Pfizer Inc.REC name
East of England - Essex Research Ethics Committee
REC reference
20/EE/0254
Date of REC Opinion
22 Dec 2020
REC opinion
Further Information Favourable Opinion