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

Primary Purpose

Neurofibromatosis 2

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
RAD001
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurofibromatosis 2 focused on measuring Neurofibromatosis Type 2 with Vestibular Schwannoma, Vestibular Schwannoma, Peripheral Nervous System Diseases, Otorhinolaryngologic Diseases, Vestibulocochlear Nerve Diseases

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Beaujon, 100 boulevard du Général Leclerc

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

Patient with Neurofibromatosis Type 2 and Vestibular Schwannoma treated with RAD001.

Outcomes

Primary Outcome Measures

effect of RAD001 on the VS growth by MRI
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

Effect of RAD001 on the volume of other intracranial tumors (MRI) and on hearing function (audiogram)
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

Full Information

First Posted
November 30, 2011
Last Updated
May 22, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT01490476
Brief Title
Efficacy and Safety Study of RAD001 in the Growth of the Vestibular Schwannoma(s) in Neurofibromatosis 2 (NF2) Patients
Acronym
AFINF2
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 Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis 2
Keywords
Neurofibromatosis Type 2 with Vestibular Schwannoma, Vestibular Schwannoma, Peripheral Nervous System Diseases, Otorhinolaryngologic Diseases, Vestibulocochlear Nerve Diseases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001
Arm Type
Experimental
Arm Description
Patient with Neurofibromatosis Type 2 and Vestibular Schwannoma treated with RAD001.
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Afinitor / rapamycin
Intervention Description
10 mg per os / day or 05mg per os / day with 12 month
Primary Outcome Measure Information:
Title
effect of RAD001 on the VS growth by MRI
Description
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
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Effect of RAD001 on the volume of other intracranial tumors (MRI) and on hearing function (audiogram)
Description
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
Time Frame
1, 2 and 4 years after inclusion in the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel Kalamarides, Professor
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Beaujon, 100 boulevard du Général Leclerc
City
Clichy
ZIP/Postal Code
92110
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
25567352
Citation
Goutagny S, Raymond E, Esposito-Farese M, Trunet S, Mawrin C, Bernardeschi D, Larroque B, Sterkers O, Giovannini M, Kalamarides M. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neurooncol. 2015 Apr;122(2):313-20. doi: 10.1007/s11060-014-1710-0. Epub 2015 Jan 8.
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Efficacy and Safety Study of RAD001 in the Growth of the Vestibular Schwannoma(s) in Neurofibromatosis 2 (NF2) Patients

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