Status:

COMPLETED

Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

Lead Sponsor:

NYU Langone Health

Conditions:

Neurofibromatosis Type 2

Vestibular Schwannomas

Eligibility:

All Genders

18+ years

Phase:

EARLY_PHASE1

Brief Summary

The primary objective is to estimate the proportions of vestibular schwannomas (VS) and meningiomas after 10 days of exposure to the study drug RAD001 at a dose of 10 mg daily, as determined by immuno...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

June 1 2013

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 1 2019

Estimated Enrollment :

5 Patients enrolled

Trial Details

Trial ID

NCT01880749

Start Date

June 1 2013

End Date

December 1 2019

Last Update

May 13 2020

Active Locations (1)

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Page 1 of 1 (1 locations)

1

New York University School of Medicine

New York, New York, United States, 10016