Neurofibromatosis Type 2Phase 2NCT01345136
Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma
A Phase 2 study testing RAD001, everolimus in people with Neurofibromatosis Type 2 and Neuroma, Acoustic, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Neurofibromatosis Type 2, Neuroma, Acoustic
- What is being tested?
- RAD001, everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2015to 6 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Los Angeles
Los Angeles, California, 90095-7286
About this study
Official title: A Single Arm, Monocenter Phase II Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis Type 2 - Related Vestibular Schwannoma
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.
Read the 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).
- Conditions
- Neurofibromatosis Type 2, Neuroma, Acoustic
- Being tested
- RAD001, everolimus
- Keywords
- Neurofibromatosis Type 2, Vestibular schwannoma, Hearing
- Medical subject headings
- Neurofibromatosis 2, Neuroma, Acoustic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001, everolimusDrug
Also called Everolimus, Afinitor
Adults: 10 mg p.o. daily dose, age 16 - 17: 3.0 mg/m2 p.o. daily
| Study group | Role | What they receive |
|---|---|---|
| RAD001 Treatment | Experimental | All subjects will be given RAD001 for 1 year (12 months). Receives: Drug: RAD001, everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vestibular schwannoma volume
Determine the effect of RAD001 on change in vestibular schwannoma volume (mm3) by MRI from baseline to 1 year.
Measured: 1 year (12 months)
Secondary outcomes (2)
Hearing
Determine the effects of RAD001 treatment on hearing changes (from baseline to 1 year in the ear with the growing vestibular schwannoma.
Measured: 1 year (12 months)
Number of adverse events
Determine the number of study subjects with adverse events by grade of severity
Measured: 1 year, 1 month (13 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2011 (estimated)
- Study start1 Jul 2015
- Primary completion6 Feb 2024
- Study completion6 Feb 2024
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis Type 2Studies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Marco Giovannini, MD, PhD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01345136
- Sponsor's protocol ID
- 13-001492
- Status last verified
- Feb 2024
- First submitted
- 21 Apr 2011
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24414536Goutagny 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.
PubMed 25567352Nghiemphu PL, Vitte J, Dombi E, Nguyen T, Wagle N, Ishiyama A, Sepahdari AR, Cachia D, Widemann BC, Brackmann DE, Doherty JK, Kalamarides M, Giovannini M. Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma. J Neurooncol. 2024 Apr;167(2):339-348. doi: 10.1007/s11060-024-04596-4. Epub 2024 Feb 19.
PubMed 38372904
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Monocenter Phase II Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis Type 2 - Related Vestibular Schwannoma
- ClinicalTrials.gov ID
- NCT01345136
- Acronym / sponsor ID
- 13-001492
- Conditions
- Neurofibromatosis Type 2, Neuroma, Acoustic
- Keywords
- Neurofibromatosis Type 2, Vestibular schwannoma, Hearing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 1 Jul 2015 (actual)
- Primary completion
- 6 Feb 2024 (actual)
- Study completion
- 6 Feb 2024 (actual)
- First posted
- 29 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 Treatment | Experimental | Drug: RAD001, everolimusAll subjects will be given RAD001 for 1 year (12 months). |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001, everolimusAlso: Everolimus, AfinitorAdults: 10 mg p.o. daily dose, age 16 - 17: 3.0 mg/m2 p.o. daily | Drug | RAD001 Treatment |
Primary outcome
Vestibular schwannoma volume
Time frame: 1 year (12 months)
Determine the effect of RAD001 on change in vestibular schwannoma volume (mm3) by MRI from baseline to 1 year.
2 secondary outcomes
Hearing
Time frame: 1 year (12 months)
Number of adverse events
Time frame: 1 year, 1 month (13 months)
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Background: PubMed 24414536Giovannini 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.
- Background: PubMed 25567352Goutagny 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.
- Derived from this study: PubMed 38372904Nghiemphu PL, Vitte J, Dombi E, Nguyen T, Wagle N, Ishiyama A, Sepahdari AR, Cachia D, Widemann BC, Brackmann DE, Doherty JK, Kalamarides M, Giovannini M. Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma. J Neurooncol. 2024 Apr;167(2):339-348. doi: 10.1007/s11060-024-04596-4. Epub 2024 Feb 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Giovannini, MD, PhD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RAD001, everolimus in people with Neurofibromatosis Type 2 and Neuroma, Acoustic, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vestibular schwannoma volume (time frame: 1 year (12 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01345136, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2024.