Phase II Study of Everolimus (RAD001) in Children and Adults With Neurofibromatosis Type 2

NCT01419639 | Completed Phase 2 Results DMC

• 2 other identifiers: RAD001 NF2 (11-00587)2010-10-011
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies whether Everolimus is efficacious in treating neurofibromatosis 2.

Conditions

Neurofibromatosis Type II

Keywords

Neurofibromatosis Type II; cranial nerve schwannomas; meningiomas; ependymomas

Outcome Measures

Primary Outcomes (2)

• Radiographic Response

  To estimate the objective response rates to RAD001 in patients with NF2-related tumors including cranial nerve schwannomas, meningiomas and ependymomas. Radiographic response for study purposes = greater than or equal to 15% reduction in tumor volume in any of the target tumors (partial response). Complete disappearance of any of the target tumors = complete response. MRI of the brain and spine will be performed every 3 months. If an objective response (15% reduction in tumor volume compared to baseline) is observed in any target tumor or stable disease, drug will be continued.

  1 Year

• Change in Tumor Size From Baseline

  1 Year

Secondary Outcomes (1)

• Audiologic Response

  1 Year

Study Arms (1)

RAD001

EXPERIMENTAL

RAD001 taken orally continuously until disease progression or unacceptable toxicity, dosed according to age

Drug: Everolimus (RAD001) , Afinitor®

Interventions

Everolimus (RAD001) , Afinitor® DRUG

Everolimus will be provided by Novartis. Everolimus is formulated as tablets for oral administration of 2.5 mg, 5 mg, 10 mg strength. Everolimus will be self-administered (by the patients themselves) or administered by the patient's parent or guardian (for minors). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. Depending the age-based dosing schedule, everolimus should be administered orally once (or twice) daily, preferably in the morning (and evening), at the same time every day with our without food. Everolimus tablets should be swallowed whole with a glass of water. The tablets must not be chewed or crushed. In cases where tablets can not be swallowed, the tablets should be disintegrated in water just prior to being taken. Everolimus will be administered orally as per the age-based dosing schedule continuously from study day 1 until progression of disease or unacceptable toxicity.

Also known as: Afinitor®

RAD001

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 3 years and body surface area ≥ 0.5 m2
• Meets diagnostic criteria for NF2
• At least one volumetrically measurable and ≥ 0.5 cc NF2-related brain or spinal tumor (schwannoma, ependymoma, meningioma - histological confirmation not required) with radiographic evidence of progression (either as unequivocal progression on conventional MRI, or a \>10% volume increase by 3D volumetrics) over the past ≤12 months, designated as the primary target tumor OR Volumetrically measurable and ≥ 0.5 cc VS with ipsilateral progressive hearing loss over the past ≤12 months, designated as the primary target tumor
• Progressive Hearing Loss Criteria for Enrollment: Audiogram showing drop in pure tone average (PTA) of 10dB HL at ≥ 2 nonconsecutive or consecutive frequencies or drop in speech discrimination score (SDS) below the 95% critical difference threshold, compared to previous audiogram ≤ 1 year prior.
• Karnofsky/Lansky performance status (PS) 50-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \> 9 g/dL
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x ULN
• ALT and AST ≤ 2.5x ULN
• INR ≤ 1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for \>2 weeks at time of enrollment.)
• Adequate renal function: serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
• Any neurologic deficits must be stable for ≥ 1 week
• Able to provide signed informed consent (or consent by parent/legal guardian for minors)

You may not qualify if:

• Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, antibody based therapy, etc.)
• Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment.
• Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
• severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN (Note: Optimal glycemic control should be achieved before starting trial therapy.)
• active (acute or chronic) or uncontrolled severe infections
• liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

Sponsors & Collaborators

• NYU Langone Health: lead
• Novartis Pharmaceuticals: collaborator
• The Children's Tumor Foundation: collaborator

Study Sites (1)

New York University Medical Center

New York, New York, 10016, United States

Location

Related Links

• New York University Medical Center

MeSH Terms

Conditions

Neurofibromatosis 2; Meningioma; Ependymoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neuroma, Acoustic; 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; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Glioma; Neoplasms, Neuroepithelial; Neoplasms, Glandular and Epithelial

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Matthias A. Karajannis
• Organization: NYU Langone Medical Center

matthias.karajannis@nyumc.org

212 263 9959

Study Officials

• Matthias A Karajannis, MD, MS

  New York University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2011
• First Posted: August 18, 2011
• Study Start: October 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2013
• Last Updated: July 18, 2017
• Results First Posted: August 7, 2015

Record last verified: 2017-06

Locations

US (1)