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This study examined the drug Binimetinib in children and adults with plexiform neurofibromas caused by neurofibromatosis type 1 (NF1) that were progressive or causing significant problems. It enrolled patients aged 18 and older who had an NF1 diagnosis and a measurable neurofibroma. It was carried out in Phase 2 and has been completed.
The summary above is a plain-language rendering of the official record. The original English title is shown for reference.
Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.
Inclusion Criteria * 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 * 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. Exclusion Criteria * 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 * 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.