None listed
Conditions
Interventions
Drug : 1. Subject Screening and Enrollment
Patients who meet the study eligibility criteria will receive a full explanation of the study, and those who voluntarily provide informed consent will be enr
however, treatment may be discontinued or extended at the investigator’s discretion.
4. Dose Modification, Treatment Discontinuation, and Retreatment
1) Dose Modification
- If toxicity meeting dose
Sponsors
Samsung Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Common Inclusion Criteria 1) Male or female patients aged =19 years 2) Patients histologically diagnosed with a brain tumor or metastatic brain tumor 3) Patients confirmed to have a BRAF alteration (point mutation or fusion mutation) 4) Patients who voluntarily agree to participate in the study and provide written informed consent 5) Patients with an expected survival of at least 3 months 6) Patients with an ECOG performance status of 0–2 7) Patients with adequate organ function confirmed by laboratory tests performed within 14 days prior to the first dose, meeting all of the following criteria: ? ANC = 1.5 × 10?/L ? Hemoglobin = 9 g/dL ? Platelet count = 100 × 10?/L ? PT/INR and aPTT = 1.5 × ULN ? Total bilirubin = 1.5 × ULN (= 3 × ULN in patients with Gilbert’s syndrome) ? AST and ALT = 2.5 × ULN (= 5 × ULN in patients with liver metastases) ? Alkaline phosphatase = 2.5 × ULN (= 5 × ULN in patients with liver or bone metastases) ? Albumin = 2.5 g/dL ? Amylase = 1.5 × ULN ? Serum creatinine = 1.5 × ULN or creatinine clearance (CrCl) > 50 mL/min (Cockcroft-Gault formula) 8) Women of childbearing potential and men with partners of childbearing potential must agree to use highly effective contraception during the study period and for 3 months after the last dose of study drug. Women of childbearing potential must either be surgically sterile or have a negative pregnancy test during screening. Acceptable contraceptive methods include: ? Hormonal contraception ? Intrauterine device (IUD) or intrauterine system (IUS) ? Vasectomy or bilateral tubal ligation ? Complete abstinence ? Barrier methods (e.g., male or female condoms; use of at least two barrier methods is recommended if barrier methods are used alone) 2. Inclusion Criteria (Cohort 1) 1) Patients with BRAF-mutant primary brain tumors for whom no available local treatment options (e.g., surgery or radiotherapy) exist, or who have radiologically confirmed recurrence or progression after standard treatment (e.g., surgery, CCRT), making standard therapy inappropriate or unavailable. 3. Inclusion Criteria (Cohort 2) 1) Patients with metastatic brain tumors arising from BRAF-mutant solid tumors 2) Patients with radiologically confirmed disease progression after standard treatment for the primary cancer type, or whose disease is refractory to conventional therapies, regardless of prior exposure to BRAF-targeted therapy, and who have no suitable or available local treatment options (e.g., surgery or radiotherapy) 3) Patients with at least one measurable lesion according to the RANO criteria (maximum of 5 lesions permitted)
Exclusion criteria
Exclusion criteria: 1. Common Exclusion Criteria 1) History of hypersensitivity to agents of the same class as BRAF inhibitors (prior treatment with BRAF inhibitors is allowed). 2) Patients with hematologic malignancies or double primary cancers at screening. However, the following conditions are permitted: ? Successfully treated cervical carcinoma in situ with at least 1 year elapsed since treatment ? Papillary thyroid carcinoma treated with curative resection ? Resected cutaneous squamous cell carcinoma 3) Patients meeting any of the following conditions: ? Receipt of an investigational drug within 28 days or within 5 half-lives prior to the first dose of study drug ? Major surgery within 28 days prior to the first dose ? Newly initiated or recently increased systemic corticosteroids =10 mg/day prednisolone equivalent within 28 days prior to the first dose. Patients on a stable dose for at least 2 weeks or requiring postoperative maintenance steroids may be enrolled at the investigator’s discretion. ? Current use of systemic immunosuppressants or requirement for continuous immunosuppressive therapy during the study period. Topical agents, inhaled sprays, eye drops, and local injections are permitted. ? Prior receipt of more than five anticancer treatment regimens 4) Presence of unresolved adverse events of CTCAE Grade =2 related to prior therapy at screening (except alopecia). 5) Patients with any of the following cardiovascular conditions: ? Mean QTcF >440 msec ? NYHA Class III or IV heart failure ? Cardiac metastases ? Uncontrolled electrolyte abnormalities (hyponatremia, hypokalemia, hypocalcemia, or hypomagnesemia) ? History within 6 months prior to study drug administration of unstable angina, myocardial infarction, acute coronary syndrome, uncontrolled arrhythmia (except sinus arrhythmia or controlled atrial fibrillation for =30 days), symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack ? Coronary angioplasty, coronary/peripheral artery bypass graft, or stent placement within 6 months prior to study drug administration ? Congenital long QT syndrome or clinically significant CTCAE Grade =2 ventricular or atrial dysrhythmias 6) Patients with any of the following ophthalmologic conditions: ? History or presence of retinal vein occlusion (RVO), central serous retinopathy (CSR), or neovascular macular degeneration ? Glaucoma with intraocular pressure =21 mmHg 7) Current or prior interstitial lung disease (ILD), drug-induced ILD, or radiation pneumonitis requiring steroid treatment. 8) Uncontrolled hypertension. 9) Uncontrolled infectious or neurologic diseases, active infections requiring intravenous antibiotics, known HIV infection, active hepatitis B virus (HBV), or active hepatitis C virus (HCV) infection. 10) Inability to swallow oral tablets or presence of conditions interfering with study drug administration or metabolism, including refractory nausea/vomiting, malabsorption, external biliary shunt, significant small bowel resection, clinically significant gastrointestinal bleeding, acute pancreatitis, or diverticulitis within 28 days prior to study drug administration. 11) Requirement for continuous use of CYP2C8 substrate drugs (e.g., amodiaquine) or rifampin. 12) Known or suspected substance abuse or alcohol abuse. 13) Inability to comply with protocol requirements or follow-up due to psychological, social, geographic, mental, or congenital conditions. 14) Pregnant or breastfeeding women, or women of chil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cohort 1 – Primary Brain Tumors. 6-month Progression-Free Survival (6-month PFS): The proportion of patients who are alive without disease progression at 6 months from the date of first study drug administration, as assessed according to RANO (Response Assessment in Neuro-Oncology) version 2.0 criteria.;Cohort 1 – Primary Brain Tumors. Confirmed Objective Response Rate (cORR): The proportion of patients achieving a confirmed complete response (CR) or partial response (PR), confirmed by two consecutive assessments according to the RANO (Response Assessment in Neuro-Oncology) version 2.0 criteria.;Cohort 2 – Metastatic Brain Tumors. Central Nervous System Objective Response Rate (CNS ORR): The proportion of patients achieving an intracranial response in CNS lesions, as assessed by the RANO-BM criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Progression-Free Survival (PFS);Disease Control Rate (DCR);Objective Response Rate (ORR): Calculated based on the assessment of complete response (CR) and partial response (PR) using Methionine PET metabolic tumor volume (MTV).;Central Nervous System Progression-Free Survival (CNS PFS);Extracranial (EC) Lesion Response Rate (RR) and Objective Response Rate (ORR): Assessed according to RECIST version 1.1 criteria. | — |
Countries
Korea, Republic of
Contacts
Public ContactHyun Ae Jung
Samsung Medical Center
Outcome results
None listed