MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1

Inclusion Criteria

• All studies to determine eligibility must be performed within 2 weeks prior to enrollment unless otherwise indicated below. All clinical and laboratory data required for eligibility of a subject must be available in the subject's medical or research record.
• All subjects must have EITHER the clinical diagnosis of NF1 using the NIH Consensus Conference criteria OR have a constitutional NF1 mutation documented in a CLIA/CAP certified lab.
• Subjects must have plexiform neurofibroma(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing major deformity (e.g., orbital lesions) or are significantly disfiguring lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Subjects with paraspinal plexiform neurofibromas will be eligible for this trial. Histologic confirmation of tumor is not necessary in the presence of consistent clinical and radiographic findings
• For subjects enrolled for tumor progression, progression is defined as:
• Presence of new plexiform neurofibroma on MRI or CT (documented by comparison with prior MRI or CT), OR
• A measurable increase in plexiform neurofibroma size (≥ 20% increase in the volume, or a ≥ 13% increase in the product of the two longest perpendicular diameters, or a ≥ 6% increase in the longest diameter) documented by comparison of two scans (MRI or CT) approximately one year or less prior to evaluation for this study.
• For subjects enrolled for a "major deformity" or "significantly disfiguring" tumor, eligible tumors will be limited to tumors of the head & neck or those on other areas of the body that are unable to be concealed by standard garments. In order to enroll a plexiform neurofibroma for these indications, the Study Chair or Co-Chair must be contacted to review subject eligibility prior to enrollment.
• Measurable disease: Subjects must have measurable plexiform neurofibroma(s) amenable to volumetric MRI analysis. The target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PNs 3 cm in longest diameter will meet this criteria). If the tumor is 21 mmHg, or any other significant abnormality on ophthalmic examination (performed by an ophthalmologist).
• Ophthalmological findings secondary to long-standing Optic Pathway Glioma such as optic nerve pallor or strabismus will NOT be considered significant for the purposes of the study.
• Tumor not able to be reliably evaluated by volumetric analysis.
• 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.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of PD-0325901 (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed.
• Women who are pregnant or breast feeding.
• Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the period they are receiving the study drug and for 3 months thereafter. Abstinence is an acceptable method of birth control. Women of childbearing potential will be given a pregnancy test within 7 days prior to administration of PD-0325901 and must have a negative urine or serum pregnancy test.
• History of noncompliance to medical regimens.
• Subjects unwilling to or unable to