Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations (NCT03839342) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Binimetinib and Encorafenib for the Treatment of Advanced Solid Tumors With Non-V600E BRAF Mutations
Canada26 participantsStarted 2019-06-07
Plain-language summary
This is a single-centre, open-label Phase II study of the investigational drugs binimetinib and encorafenib that will be taken my mouth (orally) daily in adult patient with advanced and/or metastatic solid tumors for which no other standard therapy is available. The main purpose is to evaluate the objective response rate (ORR) of the study drugs in the growth of the cancer in patients with class 2 and 3 BRAF mutations.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Signed written and voluntary informed consent.
. Patient must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
. Age \> 18 years, male or female.
. Patient must be diagnosed with a histologically or cytologically-documented, locally-advanced, or metastatic solid malignancy that is incurable and has either (a) failed prior standard therapy, (b) for which no standard therapy exists, or (c) standard therapy is not considered appropriate by the patient and treating physician.
. Measurable disease by RECIST v1.1 criteria.
. Malignancy must express one of the following BRAF alterations: BRAF mutation affecting codon: 241, 257, 367, 462, 463, 464, 466, 467, 469, 485, 581, 586, 594, 595, 596, 597 598, 599, 601; V600 BRAF mutations: V600K (for any malignancy except melanoma), V600D, V600M, V600R; BRAF deletions ie. V600\_K601delinsE or 1799\_1801 del TGA; BRAF insertions ie. T599dup; BRAF fusions ie. KIAA1549:BRAF
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Objective response rate defined as per RECIST v1.1.
. All patients enrolled must be willing and able to provide at least 1 archival and/or fresh tumor biopsy at baseline for histopathological and molecular evaluation during the screening period with binimetinib and encorafenib. Additional matched pre-treatment and on-treatment fresh tumor biopsies are mandatory for 10 patients enrolled in stage 2. Any patient with insufficient or inadequate archival tissue samples will be required to provide a fresh tumor biopsy. For all other patients, a fresh baseline biopsy is optional, but highly recommended. If a patient only has a single measurable lesion by RECIST v1.1, this lesion can be used for baseline biopsy if it is 2cm or greater.
. Patient must be able to swallow pills
Exclusion criteria
. Any patient with a tumor expressing a BRAF V600E mutation
. Any patient with melanoma whose tumor expresses a BRAF V600K mutation
. Prior therapy with any BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or any MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib).
. Patients receiving any systemic chemotherapy, immunotherapy, or targeted therapy, within 4 weeks from the last dose prior to study treatment. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment. Local treatment (e.g. by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable within 2 weeks, with prior consultation and in agreement with the principal investigator.
. Any symptomatic brain metastasis Note: Patients previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable for ≥ 4 weeks, with imaging (e.g., magnetic resonance imaging \[MRI\] or computed tomography \[CT\]) demonstrating no current evidence of progressive brain metastases at screening.
. History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
. Leptomeningeal disease
. Previous or concurrent malignancy within 3 years of study entry, with the following exceptions: adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; other solid tumors treated curatively without evidence of recurrence for at least 3 years prior to study entry (note: based on mechanism of action, BRAF inhibitors may cause progression of cancers associated with RAS mutations)