Binimetinib, Encorafenib and Pembrolizumab COmbination in MElanoma - Metastatic to the Brai
- Conditions
- BRAF(V600) mutation-positive melanoma with brain metastasis (MBM)MedDRA version: 20.0Level: LLTClassification code: 10027481Term: Metastatic melanoma Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-505302-42-00
- Lead Sponsor
- nicancer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
Provided written informed consent prior to any trial specific procedures., At least one measurable intracranial lesion, All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values) must be resolved or Grade 1 according to National Cancer Institute – Common terminology criteria for adverse events, version 5.0 (NCI-CTCAE v5.0)., Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption (malabsorption syndrome, major resection of the stomach or bowels)., Adequate bone marrow, organ function, and laboratory parameters., Adequate cardiac function, Women of childbearing potential (WOCBP) or men must agree to refrain from sexual activity or use adequate contraception for the duration of study treatment and for 120 days after completing treatment. Male participants must agree to refrain from donating sperm during this period., Affiliated to or a beneficiary of the local social security system or equivalent., Patient is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up., Aged =18 years old., An Eastern Cooperative Oncology Group (ECOG) performance status of 0-1., Histologically confirmed Stage IV M1d cutaneous melanoma or unknown primary melanoma that is metastatic to the brain. Patients with mucosal melanomas are not considered eligible for this study., Presence of BRAFV600E/K/D/R mutation according to a locally validated BRAF Assay., Candidacy for SRS therapy validated by the radiation oncologist and neurosurgeon at the investigative centre. This should be documented in the patient file., Absence of previous combined systemic treatment for distant metastatic melanoma., No more than one previous local intracranial therapy for one lesion (e.g. craniotomy, SRS)., Able to undergo gadolinium-enhanced magnetic resonance imaging (MRI).
More than 10 intracranial metastases., Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (patients with laboratory evidence of cured HBV and/or HCV will be permitted)., A history or evidence of cardiovascular risk, A history or current evidence of retinal vein occlusion., Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, and their excipients., Hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption, Participation in another therapeutic trial within the 30 days prior to randomization, Pregnant or breastfeeeding female., History of, or active interstitial lung disease or (non-infectious) pneumonitis., Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease (Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll)., Diagnosis of immunodeficiency or systemic chronic steroid therapy (=10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed., Presence of neurological symptoms related to intracranial metastases which induce alteration of the ECOG performance status to 2 or more or require immediate radiation treatment., Has received a live vaccine within 30 days prior to the first dose of study drug., Active infection requiring systemic therapy., Known history of active TB (Bacillus Tuberculosis)., Allogenic tissue/solid organ transplant., Person deprived of their liberty or under protective custody or guardianship., Patient unwilling or unable to comply with the medical follow-up required by the trial because of geographic, social or psychological reasons., Ocular melanoma., Brain metastases that necessitate immediate neurosurgery., Any previous treatment with whole-brain radiation., Presence of leptomeningeal disease or any parenchymal brain metastasis >30 mm in longest diameter., Current or expected use of a strong inhibitor of CYP3A4., History of malignancy other than disease under study occurring within 3 years of study enrolment with the exception of completely resected non-melanoma skin cancer or indolent second malignancies., Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could interfere with the patient’s safety, obtaining informed consent, or compliance with study procedures.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method