Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

NCT01880749 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 12-02808
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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 immunohistochemistry. This is a "phase 0" PK (pharmacokinetic) and PD (pharmacodynamic) study of RAD001 in patients with Neurofibromatosis Type 2-related and sporadic VS and meningiomas. Enrolled patients will take RAD001 prior to a scheduled VS or meningioma surgery, and blood and tissue samples will be obtained for further analysis.

Conditions

Neurofibromatosis Type 2; Vestibular Schwannomas; Meningiomas

Outcome Measures

Primary Outcomes (1)

• Proportions of VS and meningiomas after exposure to RAD001

  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.

  10 days

Study Arms (1)

RAD001

EXPERIMENTAL

RAD001 taken by mouth 10mg daily for 10 days before surgery

Drug: RAD001

Interventions

RAD001 DRUG

Also known as: Everolimus

RAD001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 2; Neuroma, Acoustic; Meningioma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Theodore Nicolaides, MD

  NYU Langone Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 19, 2013
• Study Start: June 1, 2013
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: May 13, 2020

Record last verified: 2020-05

Locations

US (1)