Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
Primary Purpose
Neurofibromatosis Type 2, Neuroma, Acoustic
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RAD001, everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Neurofibromatosis Type 2 focused on measuring Neurofibromatosis Type 2, Vestibular schwannoma, Hearing
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of NF2 by National Institutes of Health (NIH) criteria
- Age ≥ 16 years
- Progressive VS growth during the previous 12 months.
- WHO performance status > or = 2
- 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.
- Presence of a fungal infection requiring systemic antifungal treatment at enrollment
- 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
- University of California Los Angeles
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RAD001 Treatment
Arm Description
All subjects will be given RAD001 for 1 year (12 months).
Outcomes
Primary Outcome Measures
Vestibular schwannoma volume
Determine the effect of RAD001 on change in vestibular schwannoma volume (mm3) by MRI from baseline to 1 year.
Secondary Outcome Measures
Hearing
Determine the effects of RAD001 treatment on hearing changes (from baseline to 1 year in the ear with the growing vestibular schwannoma.
Number of adverse events
Determine the number of study subjects with adverse events by grade of severity
Full Information
NCT ID
NCT01345136
First Posted
April 21, 2011
Last Updated
February 7, 2023
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01345136
Brief Title
Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
Official Title
A Single Arm, Monocenter 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
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
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. Secondary objectives include determining if RAD001 treatment will improve hearing ability in NF2 patients.
RAD001 is an oral drug that is approved by Food and Drug Administration (FDA) for other types of tumors, it is not approved by the FDA for treatment of NF2 related tumors.
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, and to assess the effect of RAD001 on hearing function in patients with NF2 (when applicable).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis Type 2, Neuroma, Acoustic
Keywords
Neurofibromatosis Type 2, Vestibular schwannoma, Hearing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RAD001 Treatment
Arm Type
Experimental
Arm Description
All subjects will be given RAD001 for 1 year (12 months).
Intervention Type
Drug
Intervention Name(s)
RAD001, everolimus
Other Intervention Name(s)
Everolimus, Afinitor
Intervention Description
Adults: 10 mg p.o. daily dose, age 16 - 17: 3.0 mg/m2 p.o. daily
Primary Outcome Measure Information:
Title
Vestibular schwannoma volume
Description
Determine the effect of RAD001 on change in vestibular schwannoma volume (mm3) by MRI from baseline to 1 year.
Time Frame
1 year (12 months)
Secondary Outcome Measure Information:
Title
Hearing
Description
Determine the effects of RAD001 treatment on hearing changes (from baseline to 1 year in the ear with the growing vestibular schwannoma.
Time Frame
1 year (12 months)
Title
Number of adverse events
Description
Determine the number of study subjects with adverse events by grade of severity
Time Frame
1 year, 1 month (13 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of NF2 by National Institutes of Health (NIH) criteria
Age ≥ 16 years
Progressive VS growth during the previous 12 months.
WHO performance status > or = 2
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.
Presence of a fungal infection requiring systemic antifungal treatment at enrollment
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
Marco Giovannini, MD, PhD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-7286
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24414536
Citation
Giovannini M, Bonne NX, Vitte J, Chareyre F, Tanaka K, Adams R, Fisher LM, Valeyrie-Allanore L, Wolkenstein P, Goutagny S, Kalamarides M. mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma. Neuro Oncol. 2014 Apr;16(4):493-504. doi: 10.1093/neuonc/not242. Epub 2014 Jan 10.
Results Reference
background
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.
Results Reference
background
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Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
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