Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01880749
Recruitment Status : Completed
First Posted : June 19, 2013
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Tracking Information
First Submitted Date  ICMJE June 11, 2013
First Posted Date  ICMJE June 19, 2013
Last Update Posted Date May 13, 2020
Study Start Date  ICMJE June 2013
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2013)
Proportions of VS and meningiomas after exposure to RAD001 [ Time Frame: 10 days ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
Official Title  ICMJE Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE
  • Neurofibromatosis Type 2
  • Vestibular Schwannomas
  • Meningiomas
Intervention  ICMJE Drug: RAD001
Other Name: Everolimus
Study Arms  ICMJE Experimental: RAD001
RAD001 taken by mouth 10mg daily for 10 days before surgery
Intervention: Drug: RAD001
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2017)
5
Original Estimated Enrollment  ICMJE
 (submitted: June 14, 2013)
51
Actual Study Completion Date  ICMJE December 2019
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01880749
Other Study ID Numbers  ICMJE 12-02808
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NYU Langone Health
Study Sponsor  ICMJE NYU Langone Health
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Theodore Nicolaides, MD NYU Langone Health
PRS Account NYU Langone Health
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP