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Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

Phase 0
18 Years
Open (Enrolling)
Neurofibromatosis Type 2, Vestibular Schwannomas, Meningiomas

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Trial Information

Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

Inclusion Criteria:

- Patients must satisfy all of the following eligibility criteria:

- Karnofsky performance status (KPS) ≥ 60%

- Absolute neutrophil count ≥ 1,000/mm³ (unsupported)

- Platelet count ≥ 100,000/mm³ (unsupported)

- Hemoglobin ≥ 8 g/dl (transfusion support allowed)

- Creatinine ≤ 1.5 times upper limit of normal (ULN*) OR corrected glomerular
filtration rate ≥ 70 ml/min

- Total bilirubin ≤ 1.5 times ULN*

- ALT ≤ 2.5 times ULN*

- Serum albumin ≥ 2 g/dl

- INR < 1.3 (or < 3 on anticoagulants)

- Patients taking a cholesterol-lowering agent must be on a single medication and on a
stable dose for at least 4 weeks

- Fasting serum cholesterol ≤ 300 mg/dl OR ≤ 7.75 mmol/l AND fasting triglycerides ≤
2.5 times ULN*.

- Fully recovered from acute toxic effects of any prior chemotherapy, biological
modifiers or radiotherapy

- Any neurologic deficits must be stable for ≥ 1 week

- Patients with the potential for pregnancy or impregnating their partner must agree to
follow acceptable birth control methods to avoid conception. Women of childbearing
potential must have a negative pregnancy test. The anti-proliferative activity of
this experimental drug may be harmful to the developing fetus.

- Able to provide written informed consent

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

- 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,

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Outcome Measure:

Proportions of VS and meningiomas after exposure to RAD001

Outcome Description:

1) To estimate the proportions of VS and meningiomas with complete inhibition of phospho-S6 after10 days of exposure to RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This endpoint was chosen based on prior pharmacodynamic data from a published trial, showing complete inhibition of phospho-S6 in solid tumor tissue of patients treated with RAD001 and our own preliminary data confirming baseline phospho-S6 expression in VS and meningiomas.

Outcome Time Frame:

10 days

Safety Issue:


Principal Investigator

Matthias A Karajannis, MD

Investigator Role:

Study Chair

Investigator Affiliation:

New York University School of Medicine


United States: Institutional Review Board

Study ID:

S12-02808, CRAD001CUS205T



Start Date:

June 2013

Completion Date:

Related Keywords:

  • Neurofibromatosis Type 2
  • Vestibular Schwannomas
  • Meningiomas
  • Meningioma
  • Neurilemmoma
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Neurofibromatosis 2
  • Neuroma, Acoustic



New York University School of Medicine New York, New York  10016