Phase 2 Clinical Trial of Crizotinib for Children and Adults With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas

Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy and molecular targeted agents), as these may interfere with the study drug

Monoclonal antibody treatment and/or agents with prolonged half-lives: At least three half-lives must have elapsed from the last dose prior to enrollment

Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment, as these may interfere with our ability to assess response to study drug

Prior treatment with any investigational drug within the preceding 4 weeks, as they may interfere with the study drug

Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors, as this would represent a high risk for inability to comply with the study requirements

Use of drugs or foods that are known potent CYP3A4 inhibitors, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice, as this would interfere with study drug metabolism

Use of drugs that are known potent CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John's wort, as this would interfere with study drug metabolism

Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to pimozide, aripiprazole, triazolam, dihydroergotamine, ergotamine, astemizole, cisapride, terfenadine and halofantrine, as this would interfere with study drug metabolism

Ongoing cardiac dysrhythmias of CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade or prolonged QTc interval (\>480 msec), as patients with these conditions would be expected to have an increased risk for cardiac toxicity related to study drug

Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

symptomatic congestive heart failure of New York heart Association Class III or IV

unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease

severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air

active (acute or chronic) or uncontrolled severe infections liver disease, such as cirrhosis or severe hepatic impairment (Child-Pugh class C)

Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of crizotinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 90 days after the last dose of study drug, as the effects of crizotinib on an unborn fetus are not known. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of crizotinib.

Male patients whose sexual partner(s) are women of child bearing potential, who are not willing to use adequate contraception during the study and for 90 days after the last dose of study drug.

History of significant noncompliance to medical regimens that would jeopardize compliance with study therapy

Patients unwilling to or unable to comply with the study protocol

What this study is about