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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01490476
First received: November 30, 2011
Last updated: March 12, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Neurofibromatosis 2
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • effect of RAD001 on the VS growth by MRI [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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) [ Time Frame: 1 year and 2 years after inclusion in the study ] [ Designated as safety issue: No ]
    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.


Enrollment: 10
Study Start Date: January 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 1 year 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.

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. RAD001 will be continued until the end of the protocol (12 months after the assessment of the 12th month of treatment).

All patients will have a follow-up visit (including MRI) scheduled at 12 months after the last dose of the study drug.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490476

Locations
France
Hôpital Beaujon, 100 boulevard du Général Leclerc
Clichy, France, 92110
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Michel Kalamarides, Professor Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01490476     History of Changes
Other Study ID Numbers: P101202, 2011-002228-42
Study First Received: November 30, 2011
Last Updated: March 12, 2014
Health Authority: France: Ministry of Health

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:
Neurofibromatoses
Neurofibromatosis 1
Neurofibromatosis 2
Neurilemmoma
Neuroma, Acoustic
Neurofibroma
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Cranial Nerve Neoplasms
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Vestibulocochlear Nerve Diseases
Retrocochlear Diseases
Ear Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on September 18, 2014