Binimetinib in Patients With BRAF Fusion-positive Low-grade Glioma or Pancreatic Cancer (Perfume)

NCT06159478 | Recruiting Phase 2

• 1 other identifier: NCCH2101/MK011
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 6

Brief Summary

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

Keywords

BRAF fusion; BRAF rearrangement; Binimetinib

Outcome Measures

Primary Outcomes (1)

• Overall response rate (centrally assessed)

  Overall response rate (ORR) defined as the combined incidence of complete response (CR) and PR, within cohort A FAS, cohort B FAS, and confirmed no less than 4 weeks after the criteria for response are first met, based on RECIST v1.1. ORR will be confirmed by independent blinded central review assessment.

  Baseline up to 4 years

Secondary Outcomes (8)

• Overall response rate (investigator assessed by RECIST)

  Baseline up to 4 years

• Overall response rate (investigator assessed by RANO)

  Baseline up to 4 years

• Overall response rate including minor response(investigator assessed by RANO)

  Baseline up to 4 years

• Progression-free survival

  Baseline up to 4 years

• Overall survival

  Baseline up to 4 years

Study Arms (1)

Binimetinib

EXPERIMENTAL

Drug: Binimetinib 15 MG

Interventions

Binimetinib 15 MG DRUG

Binimetinib 45mg is orally administered twice daily.

Binimetinib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.
• Patients with corrected QT interval (QTcF) \> 480 ms in ECG performed within 14 days before enrollment.
• 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 history or complication of retinal degenerative disease other than RVO (central serous chorioretinopathy, retinal detachment, age-related macular degeneration, 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.).
• Prior treatment with MEK inhibitors.
• Previous severe hypersensitive reaction to ingredient including binimetinib.
• 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)

Sponsors & Collaborators

• National Cancer Center, Japan: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (6)

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Hokkaido University Hospital

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Kyoto University Hospital

Kyoto, Kyoto, 606-8507, Japan

RECRUITING

Tohoku university Hospital

Sendai, Miyagi, 980-8574, Japan

RECRUITING

National Cancer Center Japan

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Kyushu University Hospital

Fukuoka, 812-8582, Japan

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

Chigusa Morizane, M.D., Ph.D.

CONTACT

0335422511; ncch2101_office@ml.res.ncc.go.jp

Tomoyuki Satake, M.D., Ph.D.

CONTACT

ncch2101_office@ml.res.ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: December 6, 2023
• Study Start: March 29, 2023
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: December 13, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (6)