Binimetinib for Neurofibromatosis

(NF108-BINI Trial)

No longer recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests binimetinib (Mektovi) to determine its effectiveness in reducing tumor size in individuals with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas, which are tumors that grow along nerves. The goal is to achieve at least a 20% reduction in tumor volume after treatment. The study is open to those with NF1 who have tumors causing significant issues or continue to grow despite previous treatment. Participants must be able to swallow pills and have a measurable tumor that can be monitored using MRI scans. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain treatments like myelosuppressive chemotherapy within 3 weeks or an investigational drug within 4 weeks before joining the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that binimetinib is likely to be safe for humans?

Research has shown that binimetinib, a type of medication, is generally well-tolerated by both children and adults with neurofibromatosis type 1 (NF1). In a previous study, about 70% of children experienced a reduction in tumor size, suggesting that the treatment can be effective and safe for many patients.

Reported side effects include tiredness and skin rash, but these are usually mild and manageable. Importantly, the FDA has already approved binimetinib for treating certain conditions in children aged 2 and older, which supports its safety.

Overall, existing evidence supports binimetinib’s safety for people with NF1, especially since it is already used for similar conditions in children. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for neurofibromatosis?

Most treatments for neurofibromatosis focus on managing symptoms and complications through surgery or radiation. However, binimetinib offers a unique approach by targeting the MEK pathway, which is involved in cell growth and division. This targeted action has the potential to reduce tumor size more effectively, as it directly interferes with the molecular mechanisms that drive tumor growth. Researchers are particularly excited about binimetinib because it provides a non-invasive, oral treatment option that could significantly shrink tumors in a relatively short period, potentially improving patient outcomes and quality of life.

What evidence suggests that binimetinib might be an effective treatment for neurofibromatosis?

Research has shown that binimetinib may help treat neurofibromatosis type 1 (NF1) with plexiform neurofibromas. In earlier studies, patients experienced at least a 20% reduction in tumor size after completing 12 treatment cycles with binimetinib. This trial will administer binimetinib to participants to further evaluate its effectiveness. Binimetinib blocks a protein that aids tumor growth. This treatment has been well-tolerated in both children and adults, offering hope for those with NF1. ^{1 4 6 7 8}

Who Is on the Research Team?

Bruce Korf, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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

Ability to comply with follow up procedures

I can swallow pills.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7715338/

NFB-17. MEK INHIBITOR BINIMETINIB SHOWS CLINICAL ... CONCLUSIONS. Binimetinib appears reasonably well-tolerated and shows promising activity in children with NF1-associated PNs. Outcomes on ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03231306

NCT03231306 | Phase II Study of Binimetinib in Children ... The objective response to binimetinib is defined as ≥ 20% decrease in tumor volume reduction by 12 courses. Patients ≥ 1 year with progressive NF1 and PN(s) by ...

3. uab.edu uab.edu/nfconsortium/clinical-trials/bini

NF108: Binimetinib Study - Neurofibromatosis Consortium The objective response to binimetinib is defined as ≥ 20% decrease in tumor volume reduction by 12 courses. As of Protocol version 3.0, study participants who ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20454894

A Study of Binimetinib in Children and Adults With NF1 ... The objective response to binimetinib is defined as ≥ 20% decrease in tumor volume reduction by 12 courses.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-04561

Binimetinib for the Treatment of Neurofibromatosis Type 1 ... This phase II trial investigates how well binimetinib works in treating patients with neurofibromatosis type 1 associated plexiform neurofibromas.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10273716/

Treatment decisions and the use of MEK inhibitors for children ... In a phase I/II trial, most children (approximately 70%) achieved reduction in tumor volume accompanied by improvements in patient-reported ...

7. dana-farber.org dana-farber.org/clinical-trials/18-729

A Phase II Study of Binimetinib in Children and Adults ... 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 ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213756Orig1s000MultidisciplineR.pdf

213756Orig1s000 - accessdata.fda.gov Recommended Indication Treatment of pediatric patients 2 years of age and older with neurofibromatosis-1 (NF1) who have symptomatic, inoperable.