Binimetinib for BRAF fusion-positive low-grade glioma or pancreatic cancer

Trial details

Who runs it

National Cancer Center, Japan

Trial code

NCT06159478

Record updated

13 December 2023

Original description

This study is an open-label, parallel, 2-cohort, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of binimetinib in patients with advanced or recurrent low-grade glioma or pancreatic cancer harboring BRAF fusion/rearrangement.Read full original descriptionShow less

Phase II Investigator-initiated Trial of Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

This study is an open-label, parallel, 2-cohort, multicenter, investigator-initiated Phase 2 trial to evaluate the efficacy and safety of binimetinib in patients with advanced or recurrent low-grade glioma or pancreatic cancer harboring BRAF fusion/rearrangement.

Inclusion: BRAF fusion or rearrangement is detected by reimbursed NGS-based cancer gene panel tests, cancer gene panel tests performed under advanced medical treatment, or clinical study (including liquid biopsy); Unresectable or recurrent; No symptomatic brain metastasis, carcinomatous meningitis or spinal metastasis requiring surgical intervention or radiotherapy; No cardiac effusion, pleural effusion, or ascites requiring treatment; Not received anti-cancer drug within 14 days before registration, nor received other study drug (molecular targeting drug, immune therapy) within 21 days before registration; Not received operation under general anesthesia within 28 days before registration; Not received radiation therapy (including gamma knife, cyber knife) within 14 days before registration; Left ventricular ejection fraction >= 50% by echocardiography or MUGA (multigated acquisition scan) within 28 days before registration; Having all laboratory tests performed within 14 days before registration and the values are within the following range. Patients should not receive administration of G-CSF and/or blood transfusion within 14 days before the blood collection (1) Absolute neutrophil count >= 1.500/mm3 (2) Platelet count >= 10.0 X 10(4))/mm3 (3) Hemoglobin >= 8.0 g/dL (4) Total bilirubin <= 1.5 g/dL (5) Aspartate aminotransferase (AST) <= 100 U/L (6) Alanine aminotransferase (ALT) <= 100 U/L (7) Serum creatinine <= 1.5 mg/dL; Patients who are able to swallow orally administered medication; Consent to at least 30 days of contraception and limited egg donation (including egg retrieval for future egg transfer) after last administration of study drug for child-bearing status women. Consent to 90 days of contraception and limited sperm donation after last administration of study drug for men; Written informed consent (When registering patient under 18, a signed consent form must be obtained from both the patient and the parent or legal guardian.); Cohort A; Histopathologically diagnosed as low-grade glioma, based on WHO classification of 2007, 2016 and 2021. The grade is WHO grade 1 or 2; Age at the time of registration is 12 years or older (When registering a patient under 18, a signed consent form must be obtained from both the patient and the parent or legal guardian), and patients who are 12-17 years old have to be 40 kg or over in body weight. There is no limitation in body weight for patients who are 18 years or older; Lansky Performance Status (LPS) >= 70 for patients 12-15 years old Karnofsky Performance Status (KPS) >= 70 for patients 16 years or older; Having measurable disease within 28 days before registration; Patients suffice the following. (1) Having adequate initial treatment depending on the primary central nervous tumor including surgery if recommended treatment is available. (2) Neurologically stable; (3) Multiple lesion or dissemination is not detected with MRI at the registration; Not increased steroid for low-grade glioma within 14 days before registration and the dosage of steroid in equivalent to 50 mg prednisolone or less; Cohort B 19) Histopathologically diagnosed as pancreatic cancer (histologically not specified); Having progression after at least one regimen of chemotherapy excluding adjuvant therapy; Age at the time of registration is 18 years or older. 22) Performance Status (ECOG) is 0 or 1 23) Having measurable disease within 28 days before registration detected by enhanced CT (Head, chest, abdominal, pelvic: under 5 mm in slice).

Exclusion: Patients with symptomatic congestive heart failure of NYHA class II-IV or arrythmia (over grade 2) occurring in less than 6 months before registration; Patients with myocardial infarction or unstable angina occurring in less than 6 months before registration; Prior treatment with MEK inhibitors; Previous severe hypersensitive reaction to ingredient including binimetinib; Patients with concomitant diseases that affect gastrointestinal function; Active double primary cancer (but not [1]-[3]): [1] completely resected following cancers: basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, superficial bladder cancer, [2] gastrointestinal cancer curatively resected with ESD or EMR, and [3] other cancers with no recurrence for more than 5 years; Patients with infections requiring systemic treatment; Patients with uncontrolled hypertension (systolic blood pressure: over 150 mmHg or diastolic blood pressure: over 100 mmHg); Patients with history or findings of retinal vein occlusion (RVO) or having RVO risk factor (unstable glaucoma, ocular hypertension, hyperviscosity syndrome, hypercoagulability syndrome, etc.); Patients with uncontrolled diabetes mellitis; Patients with venous thrombus (transient ischemic attack, stroke, massive deep vein thrombosis, pulmonary embolism, etc.) occurring in less than 3 months; Patients who have neuromuscular disease with CK elevation (inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, etc.); Patients who are positive for either HIV antibody, HBs antigen, or HCV-RNA; Negative for HBs antigen, positive for HBs antibody or HBc antibody, and positive for HBV-DNA assay. (If it is less than or equal to the detection sensitivity, patients are not excluded); Patients with psychiatric diseases or psychological symptoms interfering with participation in the trial; Patients with corrected QT interval (QTcF) > 480 ms in ECG performed within 14 days before enrollment; Patients with history or complication of retinal degenerative disease other than RVO (central serous chorioretinopathy, retinal detachment, age-related macular degeneration, etc.); Women who are pregnant, breastfeeding and need to continue breastfeeding in the future, and women who may be pregnant; Patients who are deemed inappropriate for participation in the trial by the principal investigator or sub-investigator.

ClinicalTrials.gov NCT06159478