Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

Exclusion Criteria

• •Patients with any of the following are ineligible for this research study:
• •Patients with VS or meningiomas deemed very high surgical risk for stroke and/or other complications by the attending surgeon, such as meningiomas with major vascular or dural sinus infiltration.
• •Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
• •Symptomatic congestive heart failure or unstable angina pectoris.
• •Uncontrolled diabetes, as defined by fasting serum glucose \>1.5 times ULN\*.
• •Current active hepatic or biliary disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis (with exception of patients with Gilbert's syndrome and asymptomatic gallstones).
• •History of hepatitis B or C. Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV serology, DNA and/or HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. If no positive medical history for risk factors, serology is not required.
• •Seropositivity or DNA/RNA positivity for hepatitis B or C, with the exception of patients who have received prior Hepatitis B vaccination and are Anti-HBs positive only.
• •Known HIV seropositivity
• •Neurologic deficits that are rapidly progressing: all neurologic signs and symptoms must have been stable for a week prior to first dose
• •Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.
• •Anti-tumor therapy (i.e. chemotherapeutics or investigational agents or immunotherapy) within 4 weeks prior to enrollment
• •Radiation therapy to a study target lesion within 6 months
• •Prior therapy with mTOR inhibitors, including sirolimus, temsirolimus, deforolimus within 6 months prior to enrollment
• •Known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus, deforolimus)
• •Patients with a concurrent malignancy
• •Patients treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
• •Patients cannot receive CYP3A4 inhibiting drugs including antibiotics (clarithromycin, erythromycin, troleandomycin), anti-HIV agents (delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir), antifungals (itraconazole, ketoconazole, fluconazole at doses \> 200 mg/day, voriconazole), antidepressants (nefazodone, fluovoxamine), calcium channel blockers (verapamil, diltiazem) oramiodarone
• •Patients should avoid CYP3A4 inhibiting foods including grapefruit and Seville orange juice.
• •Patients cannot receive CYP3A4 inducing anticonvulsants including carbamazepine, felbamate, phenobarbital, phenytoin, primidone and oxcarbazepine, or other CYP3A4 inducers such as St. John's Wort
• •Patients who previously received CYP3A4 inducers or inhibitors must have discontinued these medications within at least 1 week prior to study entry and can re-start them 1 week post-operatively (or earlier if determined to be of clinical benefit, as determined by the treating physician).
• •* of institutional norms