Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Efficacy and Safety Study of RAD001 in the Growth of the Vestibular Schwannoma(s) in Neurofibromatosis 2 (NF2) Patients (AFINF2)

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. Identifier: NCT01490476
Recruitment Status : Completed
First Posted : December 13, 2011
Last Update Posted : May 23, 2017
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:
The purpose of the study is to determine if RAD001 treatment will shrink or slow the growth of the vestibular schwannoma(s) in Neurofibromatosis 2 (NF2) patients.

Condition or disease Intervention/treatment Phase
Neurofibromatosis 2 Drug: RAD001 Phase 2

Detailed Description:

This protocol is a Phase II, open-label, efficacy and safety study of single-agent RAD001 in patients with NF2. During the study, subjects will receive continuous daily oral treatment with RAD001 for up to 4 years or until tumor progression.

Primary Objective: To determine whether RAD001 has an effect on the VS growth in patients with NF2 at a rate sufficient to submit the drug for further testing.

Secondary Objectives: To determine whether RAD001 has an effect on the volume of other intracranial tumors; to assess the effect of RAD001 on hearing function in patients with NF2 (when applicable); to determine whether RAD001 modulates signaling pathways in intracranial NF2 tumors removed during the course of the study. And determine the long term safety.

All patients will be treated with RAD001 10 mg p.o. daily dose (5mg if 15-17 years old with cutaneous surface area <1.5m2) for one year except in case of unacceptable toxicity, death, or discontinuation from the study for any other reason.

At 12 months an extension for another one year of RAD001 treatment will be discussed in case of response.

If the patient is stable (decrease or increase lower than 20%), treatment should be stopped and the patient should be kept under quarterly continuous surveillance. Resumption of treatment will be discussed case by case basis if tumor regrowth over 20% relative to the tumor volume at the end of treatment.

All patients will have a follow-up visit (including MRI) scheduled at 24 months after enrollment.

We modify the protocol to extend the treatment by RAD001 for a period of two additional years for stable patients still on treatment two years after enrollment.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Single Center, Phase II Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis Type 2 - Related Vestibular Schwannoma
Study Start Date : January 2012
Actual Primary Completion Date : April 2016
Actual Study Completion Date : January 2017

Arm Intervention/treatment
Experimental: RAD001
Patient with Neurofibromatosis Type 2 and Vestibular Schwannoma treated with RAD001.
Drug: RAD001
10 mg per os / day or 05mg per os / day with 12 month
Other Name: Afinitor / rapamycin

Primary Outcome Measures :
  1. effect of RAD001 on the VS growth by MRI [ Time Frame: 1 year ]
    To determine whether RAD001 has an effect on the VS growth in patients with NF2 at a rate sufficient to submit the drug for further testing

Secondary Outcome Measures :
  1. Effect of RAD001 on the volume of other intracranial tumors (MRI) and on hearing function (audiogram) [ Time Frame: 1, 2 and 4 years after inclusion in the study ]
    To determine if RAD001 has an effect on the volume of other intracranial tumors, to assess efficacy of RAD001 on hearing function, to determine whether RAD001 modulates signaling pathways in tumors removed during the course of the study and to determine long term safety

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   15 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of NF2 by National Institutes of Health (NIH) criteria
  • Age ≥ 15 years
  • Progressive VS growth during the previous 12 months. Evidence of disease progression defined by progressive VS during the previous 12 months (>20% increase in volume) in subjects who are at elevated risk for surgical complications (eg, deafness, lower cranial nerve injury, facial weakness) or who refuse surgery
  • Adequate bone marrow, liver and renal function.
  • For women of childbearing potential, no pregnancy or breast-feeding
  • Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
  • Willingness to provide informed consent

Exclusion Criteria:

  • Inability to tolerate periodic MRI scans or gadolinium contrast.
  • Inability to tolerate periodic audiologic testing or to understand a language with established scoring for word recognition testing.
  • Inability to adequately perform volumetric measurement of at least 1 target lesionNote: Patients with cochlear or auditory brainstem implants may participate if a target lesion can be accurately assessed.
  • Radiation therapy for the target lesion in the 60 months preceding inclusion in the study.
  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug.
  • Immunization with attenuated live vaccines within one week of study entry or during study period.
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
  • 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.
  • Patients with a known hypersensitivity to everolimus or other types of rapamycin or to its excipients.
  • Patients unwilling to or unable to comply with the protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01490476

Layout table for location information
Hôpital Beaujon, 100 boulevard du Général Leclerc
Clichy, France, 92110
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Layout table for investigator information
Principal Investigator: Michel Kalamarides, Professor Assistance Publique - Hôpitaux de Paris
Layout table for additonal information
Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT01490476    
Other Study ID Numbers: P101202
2011-002228-42 ( EudraCT Number )
First Posted: December 13, 2011    Key Record Dates
Last Update Posted: May 23, 2017
Last Verified: May 2017
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neurofibromatosis Type 2 with Vestibular Schwannoma
Vestibular Schwannoma
Peripheral Nervous System Diseases
Otorhinolaryngologic Diseases
Vestibulocochlear Nerve Diseases
Additional relevant MeSH terms:
Layout table for MeSH terms
Neurofibromatosis 1
Neuroma, Acoustic
Neurofibromatosis 2
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Cranial Nerve Neoplasms
Neoplasms by Site
Vestibulocochlear Nerve Diseases
Retrocochlear Diseases
Ear Diseases
Otorhinolaryngologic Diseases