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

Trial ID: NCT06159478

Interventional - Phase 2 - Recruiting

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.

Conditions

• Low-grade Glioma
• Pancreatic Cancer

Interventions

• Binimetinib 15 MG

Eligibility

Inclusion criteria

• Inclusion criteria for both cohort A and B
• 1. 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).
• 2. Unresectable or recurrent
• 3. No symptomatic brain metastasis, carcinomatous meningitis or spinal metastasis requiring surgical intervention or radiotherapy
• 4. No cardiac effusion, pleural effusion, or ascites requiring treatment
• 5. 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
• 6. Not received operation under general anesthesia within 28 days before registration
• 7. Not received radiation therapy (including gamma knife, cyber knife) within 14 days before registration
• 8. Left ventricular ejection fraction \>= 50% by echocardiography or MUGA (multigated acquisition scan) within 28 days before registration
• 9. 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
• 10. Patients who are able to swallow orally administered medication.
• 11. 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.
• 12. 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
• 13. Histopathologically diagnosed as low-grade glioma, based on WHO classification of 2007, 2016 and 2021. The grade is WHO grade 1 or 2.
• 14. 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.
• 15. Lansky Performance Status (LPS) \>= 70 for patients 12-15 years old Karnofsky Performance Status (KPS) \>= 70 for patients 16 years or older
• 16. Having measurable disease within 28 days before registration
• 17. 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.
• 18\) 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).
• 20\) Having progression after at least one regimen of chemotherapy excluding adjuvant therapy.
• 21\) 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 criteria

• 1. 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.
• 2. Patients with symptomatic congestive heart failure of NYHA class II-IV or arrythmia (over grade 2) occurring in less than 6 months before registration.
• 3. Patients with myocardial infarction or unstable angina occurring in less than 6 months before registration.
• 4. Patients with corrected QT interval (QTcF) \> 480 ms in ECG performed within 14 days before enrollment.
• 5. Patients with infections requiring systemic treatment.
• 6. Patients with uncontrolled hypertension (systolic blood pressure: over 150 mmHg or diastolic blood pressure: over 100 mmHg).
• 7. Patients with history or findings of retinal vein occlusion (RVO) or having RVO risk factor (unstable glaucoma, ocular hypertension, hyperviscosity syndrome, hypercoagulability syndrome, etc.)
• 8. Patients with history or complication of retinal degenerative disease other than RVO (central serous chorioretinopathy, retinal detachment, age-related macular degeneration, etc.)
• 9. Patients with uncontrolled diabetes mellitis.
• 10. Patients with venous thrombus (transient ischemic attack, stroke, massive deep vein thrombosis, pulmonary embolism, etc.) occurring in less than 3 months
• 11. Patients who have neuromuscular disease with CK elevation (inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, etc.).
• 12. Prior treatment with MEK inhibitors.
• 13. Previous severe hypersensitive reaction to ingredient including binimetinib.
• 14. Patients who are positive for either HIV antibody, HBs antigen, or HCV-RNA.
• 15. 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)
• 16. Patients with concomitant diseases that affect gastrointestinal function.
• 17. Women who are pregnant, breastfeeding and need to continue breastfeeding in the future, and women who may be pregnant.
• 18. Patients with psychiatric diseases or psychological symptoms interfering with participation in the trial.
• 19. Patients who are deemed inappropriate for participation in the trial by the principal investigator or sub-investigator.

Sponsor

National Cancer Center, Japan, Ono Pharmaceutical Co., Ltd.

Source: ClinicalTrials.gov

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