Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01880749
• Date of registration: 11/06/2013
• Prospective Registration: No
• Primary sponsor: NYU Langone Health
• Public title: Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
• Scientific title: Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
• Date of first enrolment: June 2013
• Target sample size: 5
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01880749
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Early Phase 1

Countries of recruitment

United States

Contacts

• Name: Theodore Nicolaides, MD
• Affiliation: NYU Langone Health

Key inclusion & exclusion criteria

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
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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Neurofibromatosis Type 2

Vestibular Schwannomas

Meningiomas

Intervention(s)

Drug: RAD001

Primary Outcome(s)

Proportions of VS and meningiomas after exposure to RAD001 [Time Frame: 10 days]

Secondary ID(s)

12-02808

Source(s) of Monetary Support

Please refer to primary and secondary sponsors