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Neurofibromatosis Type 1Phase 2NF108-BININCT03231306

Phase II Study of Binimetinib in Children and Adults With NF1 Plexiform Neurofibromas

A Phase 2 study testing Binimetinib in people with Neurofibromatosis Type 1 and Plexiform Neurofibroma, run by University of Alabama at Birmingham at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 1 year and older
What is being tested?
Binimetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
22 sitesUnited States
Study dates
28 Nov 2017to 17 Apr 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Clinical diagnosis of NF1 using the NIH Consensus Conference criteria OR a documented constitutional NF1 mutation
  • Plexiform neurofibroma(s) that are progressive or causing significant morbidity
  • Presence of new plexiform neurofibroma on MRI or CT (documented by comparison with prior MRI or CT)
  • Measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis. Tumors must be at least 3 mL in volume (most PNs 3 cm in longest diameter will meet this criteria)
  • Patients must be ≥ 18 years of age at the time of enrollment.
  • Performance Level: Karnofsky or Lansky ≥ 50%. If unable to walk due to paralysis, but in a wheelchair, patients will be considered ambulatory for the purpose of assessing the performance level
Show all 35Show fewer
  • Ability to swallow capsules/tablets
  • Ability to comply with follow up procedures
  • The effects of binimetinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of binimetinib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Negative urine or serum β-HCG test (females of childbearing potential only).
  • Prior Therapy:
  • Patients are eligible if complete resection of a plexiform neurofibroma with acceptable morbidity is not feasible, or if a subject with surgical option refuses surgery,
  • Patients who underwent surgery for a progressive plexiform neurofibroma will be eligible to enter the study after the surgery, provided the plexiform neurofibroma was incompletely resected and is evaluable by volumetric analysis.
  • Patients previously treated for a plexiform neurofibroma or other tumor/malignancy, but must have fully recovered from the acute toxic effects of all prior chemotherapy or radiotherapy prior to entering this study.
  • Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study.
  • At least 7 days since the completion of therapy with a hematopoietic growth factor that supports platelet, red or white cell number or function.
  • At least 4 weeks since the completion of therapy with a biologic anti-neoplastic agent. For agents that have known adverse events occurring beyond 14 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
  • Patients must not have received an investigational drug within 4 weeks.
  • Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids, if necessary.
  • Radiation ≥ 6 months from involved field radiation to index plexiform neurofibroma(s), ≥ 6 weeks must have elapsed if patient has received radiation to areas outside index plexiform neurofibroma(s). Patients who have received radiation to the orbit at any time are excluded.
  • At least 3 weeks since undergoing any major surgery and must be recovered from effects of surgery.
  • Organ Function Requirements:
  • Adequate bone marrow function defined as:
  • Peripheral absolute neutrophil count (ANC) ≥ 1500/µL
  • Platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
  • Hemoglobin ≥ 10.0 gm/dL without transfusions.
  • Adequate renal function defined as:
  • Maximum serum creatinine based on age/gender or a creatinine clearance or radioisotope GFR ≥ 70 ml/min/1.73 m²
  • Adequate liver function defined as:
  • Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) ≤ 2.5 x upper limit of normal (ULN) for age
  • Serum albumin ≥ 2 g/dL
  • Adequate cardiac function defined as:
  • Left ventricular fractions (LVEF) ≥ 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
  • QTc interval ≤ 480 ms.

Who cannot join

  • Chronic treatment with systemic steroids or another immunosuppressive agent.
  • Evidence of an active optic glioma or other low-grade glioma, requiring treatment with chemotherapy or radiation therapy. Patients not requiring treatment are eligible for this protocol.
  • Patients with malignant glioma, malignant peripheral nerve sheath tumor, or other malignancy requiring treatment in the last 12 months.
  • Patients who have received radiation to the orbit at any time previously.
  • Ophthalmologic conditions:
  • Current or past history of central serous retinopathy
Show all 27Show fewer
  • Current or past history of retinal vein occlusion
  • Known intraocular pressure (IOP) > 21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma (irrespective of IOP). Patients with known glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) and are not experiencing pain related to the glaucoma, may be eligible after review. Patients with orbital plexiform neurofibromas should have IOP measured prior to enrollment.
  • Patients with any other significant abnormality on ophthalmic examination will be reviewed for potential eligibility.
  • Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study
  • Uncontrolled arterial hypertension despite medical treatment defined as CTCAE grade 3 or higher.
  • 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.
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
  • History of Gilbert's syndrome or patients who are known to be homozygous for UGT1A1 (7/7).
  • Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
  • Patients who are planning to embark on a new strenuous exercise regimen after first dose of study treatment. NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on binimetinib treatment.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to binimetinib.
  • Women who are pregnant or breastfeeding.
  • 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.
  • History of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
  • Prior treatment with a MEK inhibitor of any kind.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • National Institute of Health - National Cancer Institute

    Bethesda, Maryland, 20892

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Boston Children's Hospital / Dana Farber Cancer Institute / Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • Cinncinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Ohio State University

    Columbus, Ohio, 43210

  • Indiana University

    Indianapolis, Indiana, 46202

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • University of California at Los Angeles

    Los Angeles, California, 90095

  • New York University Medical Center

    New York, New York, 10016

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19096

  • Oregon Health and Science University Hospital

    Portland, Oregon, 97239

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of California, San Diego - Rady Children's Hospital

    San Diego, California, 92123

  • University of California, San Francisco

    San Francisco, California, 94153

  • University of Washington - Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas (PNOC010)

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.

Read the detailed description

Patients ≥ 1 year with progressive NF1 and PN(s) by serial imaging or causing significant morbidity and that can be analyzed by volumetric MRI are eligible for this study. Initially, the study will open to adult patients,18 years and older, (Stratum A). The pediatric patients (Statum B) will be receive the pediatric maximum tolerated dose (MTD) of binimetinib that is currently being established in an ongoing phase 1 study (NCT02285439). For adult subjects, binimetinib (established adult RP2D) is taken orally twice a day. Dosing will be continuous, with 28 days defined as a course and will continue for a total of 24 courses or until one of the Off Treatment or Off Study criteria are met. Subjects will undergo volumetric assays of their targeted PN using MRI after every 4 courses for the first year and then every 6 courses. MRI review of the volumetric assays will occur centrally under the guidance of Dr. Dombi at NCI. Subjects may receive additional courses beyond course 8 only if there is at least a 15% reduction in volume of the target tumor, as measured from baseline. Treatment beyond course 12 will be only be given to those subjects who achieve a response of ≥ 20% tumor shrinkage by volumetric analysis and can continue on therapy up to an additional year for a maximum of 24 total courses. For those who respond to binimetinib after 12 courses, an MRI scan of the target lesion must be performed at 4 and 12 months after stopping drug in order to determine whether response is maintained post-therapy. Subjects will be carefully monitored for development of binimetinib associated toxicities. Subjects will be removed from the study for significant toxicity, treatment delay of ≥ 21 days, or objective progression of tumor growth by ≥ 20% by volumetric analysis at any time.

The investigational nature and objectives of this trial, the procedures and treatment involved, the risks, discomforts, and benefits, and potential alternatives therapies will be carefully explained to the subject and/or subject's parent(s) or guardian by the site Principal Investigator or designated associate investigator. A signed informed consent document will be obtained prior to determining eligibility and entry criteria to this trial. Subjects entered on this trial will be treated with therapeutic intent and response to therapy will be closely monitored. This protocol involves greater than minimal risk but presents the potential for direct benefit to individual subjects.

Schedule of study evaluations are summarized below:

Pre-Study (Eligibility Screening):

  • Physical assessment, vital signs and neurological exam
  • Complete medical history including past and current medical conditions, treatments, and surgeries.
  • Karnofsky/Lansky performance status to assess of your ability to perform everyday tasks
  • Review of current medications
  • Blood draw (about two tablespoons) for routine safety tests
  • Serum or urine pregnancy test for females of childbearing age
  • Eye exam
  • Electrocardiogram (ECG) and echocardiogram (ECHO) or multigated acquisition (MUGA) scan of your heart
  • MRI of neurofibroma tumors
  • Functional evaluation: Depending on the location of your plexiform neurofibroma, specific functional assessments will be performed. The functional assessments may include a 6-Minute Walk-Test if you have a plexiform neurofibroma affecting your legs or airway, evaluation of muscle strength and range of motion if you have plexiform neurofibroma affecting your arms or legs, and/or grooved pegboard test if you have plexiform neurofibroma affecting your hands. The study team will review all evaluations that apply to you in detail
  • Completion of health-related questionnaires on quality of life, pain assessment, bowel and bladder dysfunction, and PN symptom checklist (upon study entry)
  • Photography of visible PN (optional)

End of course 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, and 24:

  • Medical history update and hospitalization since last study visit
  • Physical assessment, vital signs, and neurological exam
  • Karnofsky/Lansky performance status to assess your ability to perform everyday tasks
  • Review of your medication diary and any side effects you may be experiencing
  • Review of current medications
  • Blood draw (about two tablespoons) for routine safety tests
  • Serum or urine pregnancy test for females of childbearing age

End of course 4, 8, 12, 18, and 24:

  • Eye exam
  • MRI of neurofibromas
  • ECHO and ECG
  • Functional evaluation: (see description above)
  • Completion of health-related questionnaires on quality of life, pain assessment, bowel and bladder dysfunction, and PN symptom checklist
  • Photography of visible PN (optional): If you agree to take part, photographs of visible PN will be taken. Photos will be taken before treatment and then after cycles 4, 8, 12, 18, and 24.

End of course 1 and 4:

  • Blood draw (about one tablespoon) for cytokine studies (optional)

End of Treatment Visit (this is an additional visit if the visit is not within the specified times mentioned above):

  • Physical assessment, vital signs and neurological exam
  • Medical history update and hospitalization since last study visit
  • Karnofsky/Lansky performance status to assess of your ability to perform everyday tasks
  • Review of your medication diary and any side effects you may be experiencing
  • Review of current medications
  • Blood draw (about two tablespoons) for routine safety tests
  • Serum or urine pregnancy test for females of childbearing age
  • Eye exam
  • Electrocardiogram (ECG) and ECHO or multigated acquisition (MUGA) scan of your heart
  • MRI of neurofibroma tumors (for those who respond to binimetinib after 12 courses, an MRI at 4 and 12 months after stopping drug)
  • Functional evaluation: (see description above)
  • Completion of health-related questionnaires on quality of life, pain assessment, bowel and bladder dysfunction, and PN symptom checklist
  • Photography of visible PN (optional)

The sample size is 20 subjects for each adult and children cohorts with a minimum target of 17 evaluable subjects per cohort. Evaluable is defined as: any subjects who received ≥ one dose of binimetinib and had a ≥ Grade 3 binimetinib associated toxicity, or in absence of a ≥ Grade 3 toxicity, any subjects who completed one full course of therapy; subjects who have completed at least two courses of therapy and had their first follow-up MRI evaluation except for discovery of a target tumor other than a PN; and any subjects who has at least two samples drawn for plasma cytokines/growth factors, one at baseline and at least one other after starting therapy.

Data Safety Monitoring Board (DSMB) and a Medical Monitor have been established for this study for the purpose of ensuring data compliance and regular monitoring. An early stopping rules have been defined within the protocol. The early stopping rule will invoked for both Strata separately to potentially prevent accrual subjects onto the study in the event that binimetinib is associated with a higher than acceptable rate of dose-limiting toxicity (DLT) requiring removal from study (10% or higher) during the first 2 courses. Toxicity will be continuously monitored. If at any time >2 of the first 10 subjects or 4 or more of the first 15 total subjects are removed for toxicity, then accrual will be stopped until the DSMB reviews the safety and efficacy data for the study. Based on the review, the DSMB can either recommend termination of the study or reopen recruitment. The Medical Monitor is a qualified physician who is not associated with this protocol and is a member of the DSMB. The Medical Monitor may perform oversight functions duties: may discuss the research protocol with the investigators, interview human subjects, and consult with others outside of the study about the research; shall have the authority to stop the research protocol in progress, remove individual subjects from protocol, and take whatever steps are necessary to protect the safety and well being of human subjects until the Institutional Review Board (IRB) can assess the monitor's report; and shall have the responsibility to promptly report the observation and findings to the IRB or other designated official/organization. The Medical Monitor is specifically required to review and provide written report of all unanticipated problems involving risk to subjects or others and serious adverse events.

In addition, as part of the Data Safety Monitoring Plan, the Study Chairs and the NF Consortium Clinical Research Nurse Manager will review subject eligibility, study progress, safety issues, protocol deviations and adverse events. Monthly reports will be generated by the NF Consortium Data Management Center to assess completeness of data. Monthly phone conferences will take place between NF Consortium Operations Center and the Protocol Team to address data issues.

The sample size for this trial is based on safety and feasibility factors. The data needed for safety is based on risk versus benefit, and for feasibility, we expect at least efficacy of 25% response rate. For safety reasons, subjects who do not achieve at least 15% reduction in volume of target tumor after 8 courses will be discontinued from the trial, as the likelihood of achieving a 20% reduction in tumor volume by 12 months is minimal. Safety analysis set will be described and summarized based on information regarding study treatment administrations, drug dosing and course compliance, and safety variables (e.g. adverse events/serious adverse events). All analyses for outcome results will be based on evaluable subjects. Given the difference in the clinical behavior of PN in the adults and pediatric subjects, the adult and children stratum will be analyzed independently.

Being tested
Binimetinib
Keywords
Neurofibroma, Plexiform, Genes, Neurofibromatosis, Peripheral nerve tumors, Neurofibromatosis 1, Neurofibromas
Medical subject headings
Neurofibromatosis 1, Neurofibroma, Plexiform, Neurofibromatoses, Peripheral Nervous System Neoplasms, Neurofibroma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BinimetinibDrug

    Also called MEK162 or ARRY-438162

    Adult subjects (18 years and older) will receive binimetinib by mouth twice daily of 45mg/dose. Pediatric subjects (1-17 years of age) are being treated on the pediatric MTD established by a phase I study (NCT02285439).

Study groups in NCT03231306
Study groupRoleWhat they receive
Open label study of Binimetinib (MEK162)ExperimentalSubjects (≥ 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).
Receives: Drug: Binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline Target Tumor Volume at 12 Months

    To determine the objective response defined as 20% or greater tumor volume reduction. Patients will undergo volumetric assays of their target PN using MRI.

    Measured: Approximately 12 months

Secondary outcomes (1)

  1. Incidence of Treatment-Emergent Adverse Events

    To evaluate the toxicity of protracted binimetinib administration in this patient population. Subjects will be monitored continuously for adverse events and serious adverse events throughout the study.

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2017
  2. Study start28 Nov 2017
  3. Primary completion17 Apr 2024
  4. Study completion17 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03231306
Sponsor's protocol ID
IRB-170616001
Other IDs
516027
Acronym
NF108-BINI
Status last verified
Apr 2025
First submitted
21 Jul 2017
Last updated
2 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell. 2008 Feb;13(2):105-16. doi: 10.1016/j.ccr.2007.12.027.

    PubMed 18242511

  • Kebudi R, Cakir FB, Gorgun O. Interferon-alpha for unresectable progressive and symptomatic plexiform neurofibromas. J Pediatr Hematol Oncol. 2013 Apr;35(3):e115-7. doi: 10.1097/MPH.0b013e318270cd24.

    PubMed 23042022

  • Citak EC, Oguz A, Karadeniz C, Okur A, Memis L, Boyunaga O. Management of plexiform neurofibroma with interferon alpha. Pediatr Hematol Oncol. 2008 Sep;25(7):673-8. doi: 10.1080/08880010802315983.

    PubMed 18850480

  • Jakacki RI, Dombi E, Potter DM, Goldman S, Allen JC, Pollack IF, Widemann BC. Phase I trial of pegylated interferon-alpha-2b in young patients with plexiform neurofibromas. Neurology. 2011 Jan 18;76(3):265-72. doi: 10.1212/WNL.0b013e318207b031.

    PubMed 21242495

  • Widemann BC, Arceci RJ, Jayaprakash N, Fox E, Zannikos P, Goodspeed W, Goodwin A, Wright JJ, Blaney SM, Adamson PC, Balis FM. Phase 1 trial and pharmacokinetic study of the farnesyl transferase inhibitor tipifarnib in children and adolescents with refractory leukemias: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Feb;56(2):226-33. doi: 10.1002/pbc.22775. Epub 2010 Sep 21.

    PubMed 20860038

  • Widemann BC, Salzer WL, Arceci RJ, Blaney SM, Fox E, End D, Gillespie A, Whitcomb P, Palumbo JS, Pitney A, Jayaprakash N, Zannikos P, Balis FM. Phase I trial and pharmacokinetic study of the farnesyltransferase inhibitor tipifarnib in children with refractory solid tumors or neurofibromatosis type I and plexiform neurofibromas. J Clin Oncol. 2006 Jan 20;24(3):507-16. doi: 10.1200/JCO.2005.03.8638.

    PubMed 16421428

  • Babovic-Vuksanovic D, Widemann BC, Dombi E, Gillespie A, Wolters PL, Toledo-Tamula MA, O'Neill BP, Fox E, MacDonald T, Beck H, Packer RJ. Phase I trial of pirfenidone in children with neurofibromatosis 1 and plexiform neurofibromas. Pediatr Neurol. 2007 May;36(5):293-300. doi: 10.1016/j.pediatrneurol.2007.01.009.

    PubMed 17509460

  • Babovic-Vuksanovic D, Ballman K, Michels V, McGrann P, Lindor N, King B, Camp J, Micic V, Babovic N, Carrero X, Spinner R, O'Neill B. Phase II trial of pirfenidone in adults with neurofibromatosis type 1. Neurology. 2006 Nov 28;67(10):1860-2. doi: 10.1212/01.wnl.0000243231.12248.67. Epub 2006 Oct 11.

    PubMed 17035676

  • Kim A, Dombi E, Tepas K, Fox E, Martin S, Wolters P, Balis FM, Jayaprakash N, Turkbey B, Muradyan N, Choyke PL, Reddy A, Korf B, Widemann BC. Phase I trial and pharmacokinetic study of sorafenib in children with neurofibromatosis type I and plexiform neurofibromas. Pediatr Blood Cancer. 2013 Mar;60(3):396-401. doi: 10.1002/pbc.24281. Epub 2012 Sep 7.

    PubMed 22961690

  • Lasater EA, Bessler WK, Mead LE, Horn WE, Clapp DW, Conway SJ, Ingram DA, Li F. Nf1+/- mice have increased neointima formation via hyperactivation of a Gleevec sensitive molecular pathway. Hum Mol Genet. 2008 Aug 1;17(15):2336-44. doi: 10.1093/hmg/ddn134. Epub 2008 Apr 28.

    PubMed 18442999

  • McCormick F. Ras signaling and NF1. Curr Opin Genet Dev. 1995 Feb;5(1):51-5. doi: 10.1016/s0959-437x(95)90053-5.

    PubMed 7749326

  • Sherman LS, Atit R, Rosenbaum T, Cox AD, Ratner N. Single cell Ras-GTP analysis reveals altered Ras activity in a subpopulation of neurofibroma Schwann cells but not fibroblasts. J Biol Chem. 2000 Sep 29;275(39):30740-5. doi: 10.1074/jbc.M001702200.

    PubMed 10900196

  • Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer. 2003 Jan;3(1):11-22. doi: 10.1038/nrc969.

    PubMed 12509763

  • Weiss B, Bollag G, Shannon K. Hyperactive Ras as a therapeutic target in neurofibromatosis type 1. Am J Med Genet. 1999 Mar 26;89(1):14-22.

    PubMed 10469432

  • Wu J, Dombi E, Jousma E, Scott Dunn R, Lindquist D, Schnell BM, Kim MO, Kim A, Widemann BC, Cripe TP, Ratner N. Preclincial testing of sorafenib and RAD001 in the Nf(flox/flox) ;DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging. Pediatr Blood Cancer. 2012 Feb;58(2):173-80. doi: 10.1002/pbc.23015. Epub 2011 Feb 11.

    PubMed 21319287

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Binimetinib in people with Neurofibromatosis Type 1 and Plexiform Neurofibroma, run by University of Alabama at Birmingham at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline Target Tumor Volume at 12 Months (time frame: Approximately 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03231306, which also lists 24 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2025.

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