Binimetinib for Neurofibromatosis

(NF108-BINI Trial)

Recruiting at 23 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Systemic steroids

Disqualifiers: Active glioma, Malignant tumor, Uncontrolled hypertension, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 96 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II open label study that will evaluate children ≥ 1 year of age and adults with neurofibromatosis type 1 (NF1) and plexiform neurofibromas treated with the MEK inhibitor, binimetinib. The primary objective is to determine if there is an adequate level of disease responsiveness to binimetinib in children and adults with NF1 and inoperable plexiform neurofibromas. The objective response to binimetinib is defined as ≥ 20% decrease in tumor volume reduction by 12 courses.

Research Team

Bruce Korf, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for children over 1 year old and adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas. Participants must have a measurable tumor, be able to swallow pills, have adequate organ function, and not have had recent chemotherapy or major surgery. Pregnant women, those on chronic steroids or immunosuppressants, with certain eye conditions or uncontrolled diseases are excluded.

Inclusion Criteria

I can swallow pills.

Ability to comply with follow up procedures

Patients must not have received an investigational drug within 4 weeks

Exclusion Criteria

Any other condition that would contraindicate, in the Investigator's judgement, the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc

Impaired cardiovascular function or clinically significant cardiovascular diseases, including: History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening, Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia, Other concurrent severe and/or uncontrolled medical disease, which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration, congestive heart failure, etc.), Subjects who have an uncontrolled infection, Known positive serology for HIV (human immunodeficiency virus), active hepatitis B, and/or active hepatitis C infection

I have a muscle disorder that causes high CK levels, like muscular dystrophy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive binimetinib orally twice a day for 24 courses, with each course lasting 4 weeks

96 weeks

Regular visits at the end of each course

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRI scans at 4 and 12 months post-treatment

12 months

2 visits (in-person)

Treatment Details

Interventions

• Binimetinib

Trial Overview The study tests binimetinib, a MEK inhibitor drug, on its ability to shrink tumors by at least 20% after up to 12 treatment cycles. It's an open-label phase II trial meaning everyone gets the drug and both researchers and participants know what's being given.

Participant Groups

Group I: Open label study of Binimetinib (MEK162) Experimental Treatment 1 Intervention

Subjects (≥ 18 years) (Stratum A) will receive a course of binimetinib by mouth twice a day (12 hours apart) of 45 mg/dose. Duration of each course is 4 weeks. After 8 courses, subjects will receive additional courses if MRI results showed at least 15% reduction in volume of the target tumor. Subjects can continue on therapy and will be evaluated at the end of 12 courses. Subjects who have ≥ 20% reduction in volume of the target tumor according to the MRI results can continue therapy up to an additional year (maximum of 24 total courses). Subjects who have not met the tumor reduction at the specified times will be removed from the study therapy. Subjects will be carefully monitored for toxicities associated with binimetinib. Recruitment of subjects 1 - 17 years of age (Stratum B) is currently available. The pediatric maximum tolerated dose (MTD) of binimetinib the pediatric patients (Statum B) was established by a phase 1 study (NCT022).

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Array BioPharma

Industry Sponsor

Trials

29

Recruited

1,400+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials

16

Recruited

840+