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.
