Neurofibromatosis 2Phase 2AFINF2NCT01490476
Efficacy and Safety Study of RAD001 in the Growth of the Vestibular Schwannoma(s) in Neurofibromatosis 2 (NF2) Patients
A Phase 2 study testing RAD001 in people with Neurofibromatosis 2, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Neurofibromatosis 2
- What is being tested?
- RAD001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2012to Jan 2017
- 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 15 years and older
- 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 ≥ 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
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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single Arm, Single Center, 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.
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 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.
- Conditions
- Neurofibromatosis 2
- Being tested
- RAD001
- Keywords
- Neurofibromatosis Type 2 with Vestibular Schwannoma, Vestibular Schwannoma, Peripheral Nervous System Diseases, Otorhinolaryngologic Diseases, Vestibulocochlear Nerve Diseases
- Medical subject headings
- Neurofibromatosis 2, Neuroma, Acoustic, Peripheral Nervous System Diseases, Otorhinolaryngologic Diseases, Vestibulocochlear Nerve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
Also called Afinitor / rapamycin
10 mg per os / day or 05mg per os / day with 12 month
| Study group | Role | What they receive |
|---|---|---|
| RAD001 | Experimental | Patient with Neurofibromatosis Type 2 and Vestibular Schwannoma treated with RAD001. Receives: Drug: RAD001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Secondary outcomes (1)
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
Measured: 1, 2 and 4 years after inclusion in the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionApr 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neurofibromatosis 2Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michel Kalamarides, Professor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01490476
- Sponsor's protocol ID
- P101202
- Other IDs
- 2011-002228-42
- Acronym
- AFINF2
- Status last verified
- May 2017
- First submitted
- 30 Nov 2011
- Last updated
- 23 May 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25567352
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Single Center, Phase II Trial of RAD001 as Monotherapy in the Treatment of Neurofibromatosis Type 2 - Related Vestibular Schwannoma
- ClinicalTrials.gov ID
- NCT01490476
- Acronym / sponsor ID
- AFINF2 / P101202
- Conditions
- Neurofibromatosis 2
- Keywords
- Neurofibromatosis Type 2 with Vestibular Schwannoma, Vestibular Schwannoma, Peripheral Nervous System Diseases, Otorhinolaryngologic Diseases, Vestibulocochlear Nerve Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 13 Dec 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RAD001 | Experimental | Drug: RAD001Patient with Neurofibromatosis Type 2 and Vestibular Schwannoma treated with RAD001. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| RAD001Also: Afinitor / rapamycin10 mg per os / day or 05mg per os / day with 12 month | Drug | RAD001 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2017.
- 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.
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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.
Michel Kalamarides, Professor principal investigator
Assistance Publique - Hôpitaux de Paris
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 in people with Neurofibromatosis 2, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 7 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: finished, as of the sponsor's last update on 23 May 2017. 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 France. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
effect of RAD001 on the VS growth by MRI (time frame: 1 year). 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 NCT01490476, which also lists 1 linked publication.
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 23 May 2017.