Neurofibromatosis 2Phase 2NCT00911248
PTC299 for Treatment of Neurofibromatosis Type 2
A Phase 2 study testing PTC299 in people with Neurofibromatosis 2, run by PTC Therapeutics at 1 site in United States.
Trial summary
Formation of new blood vessels (angiogenesis) is important for tumor growth in neurofibromatosis type 2 (NF2). It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many patients with NF2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neurofibromatosis 2
- What is being tested?
- PTC299
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jul 2009to 31 Mar 2012
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Diagnosis of NF2
- Presence of vestibular schwannomas
- Evidence of progressive increase in vestibular schwannoma size or worsening hearing loss due to vestibular schwannoma
- Adequate functional status (Karnofsky Performance Score ≥60)
- Adequate bone marrow, liver, kidney function
Show all 11Show fewer
- If sexually active, willingness to use effective barrier or medical contraception
- For women of childbearing potential, no pregnancy or breast-feeding
- Discontinuation of other therapies (except corticosteroids) for the treatment of NF2 and resolution of any acute toxic effects of prior therapies
- 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
- Uncontrolled hypertension, major bleeding, HIV infection, or recent acute cardiovascular event
- Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Phase 2 Study to Assess the Efficacy, Safety, and Pharmacodynamic Activity of PTC299 in Patients With Neurofibromatosis Type 2
Formation of new blood vessels (angiogenesis) is important for tumor growth in neurofibromatosis type 2 (NF2). It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many patients with NF2. VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen. PTC299 is an oral drug that has been shown to decrease production of VEGF in animal models of human cancer. In these animal models, oral PTC299 administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood vessel numbers in the tumor, and significantly slows or halts tumor growth. Safety studies in research animals indicate good tolerability at doses and drug levels that are higher than those planned for the clinical studies. Results from Phase 1a studies in healthy volunteers indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active in animal models of human tumor. This Phase 2 study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction, antitumor activity, and hearing improvement when administered orally to patients with NF2.
Read the detailed description
The study will be conducted in 2 stages. In Stage 1 of the study, 11 patients will receive daily treatment with PTC299 administered at 100 mg/dose twice per day for up to 1 year or until tumor progression. If no subject responds with tumor shrinkage or an improvement in hearing, then the study will be stopped. If ≥1 out of 11 subjects respond, then the study will proceed to Stage 2 to enroll an additional 14 subjects for a total of 25 subjects.
- Conditions
- Neurofibromatosis 2
- Being tested
- PTC299
- Keywords
- Angiogenesis, Neurofibromatosis, Post-transcriptional control, PTC299, VEGF
- Medical subject headings
- Neurofibromatosis 2, Neurofibromatoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC299Drug
PTC299 will be administered orally at 100 mg/dose twice per day for up to 1 year or until tumor progression
| Study group | Role | What they receive |
|---|---|---|
| PTC299 | Experimental | PTC299 administered at 100 mg/dose twice per day Receives: Drug: PTC299 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2.
Measured: 48 weeks
Secondary outcomes (7)
To assess the effects of PTC299 on pure tone thresholds, brainstem auditory evoked responses (BAERs), and otoacoustic emissions (OAEs) in patients with NF2
Measured: 48 weeks
To determine if PTC299 alters the perception of tinnitus
Measured: 48 weeks
To evaluate the effects of PTC299 on tumor blood flow
Measured: 48 weeks
To assess the effects of PTC299 on concentrations of circulating angiogenic factors or cytokines
Measured: 48 weeks
To describe the PTC299 safety profile
Measured: 48 weeks
To evaluate compliance with PTC299 treatment
Measured: 48 weeks
To assess PTC299 plasma exposure over time
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study start31 Jul 2009
- Primary completion31 Mar 2012
- Study completion31 Mar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis 2Studies of the same condition, open and under way.
- 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
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Jay Barth, MD, Principal investigator, PTC Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911248
- Sponsor's protocol ID
- PTC299-ONC-007-NF2
- Other IDs
- NF080100
- Status last verified
- Apr 2019
- First submitted
- 28 May 2009
- Last updated
- 12 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study to Assess the Efficacy, Safety, and Pharmacodynamic Activity of PTC299 in Patients With Neurofibromatosis Type 2
- ClinicalTrials.gov ID
- NCT00911248
- Acronym / sponsor ID
- PTC299-ONC-007-NF2
- Conditions
- Neurofibromatosis 2
- Keywords
- Angiogenesis, Neurofibromatosis, Post-transcriptional control, PTC299, VEGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 11 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Study start
- 31 Jul 2009 (actual)
- Primary completion
- 31 Mar 2012 (actual)
- Study completion
- 31 Mar 2012 (actual)
- First posted
- 1 Jun 2009 (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.
Formation of new blood vessels (angiogenesis) is important for tumor growth in neurofibromatosis type 2 (NF2). It is known that tumors make a protein called vascular endothelial growth factor (VEGF) and there are higher levels of VEGF in the tumors and blood of many patients with NF2. VEGF stimulates the formation of blood vessels that supply the tumor with nutrients and oxygen. PTC299 is an oral drug that has been shown to decrease production of VEGF in animal models of human cancer. In these animal models, oral PTC299 administration decreases VEGF levels in the tumor and in the bloodstream, decreases blood vessel numbers in the tumor, and significantly slows or halts tumor growth. Safety studies in research animals indicate good tolerability at doses and drug levels that are higher than those planned for the clinical studies. Results from Phase 1a studies in healthy volunteers indicate that PTC299 achieves levels of PTC299 in the bloodstream that are known to be active in animal models of human tumor. This Phase 2 study is designed to test the hypothesis that PTC299 will be tolerable and will show evidence of VEGF reduction, antitumor activity, and hearing improvement when administered orally to patients with NF2.
Detailed description
The study will be conducted in 2 stages. In Stage 1 of the study, 11 patients will receive daily treatment with PTC299 administered at 100 mg/dose twice per day for up to 1 year or until tumor progression. If no subject responds with tumor shrinkage or an improvement in hearing, then the study will be stopped. If ≥1 out of 11 subjects respond, then the study will proceed to Stage 2 to enroll an additional 14 subjects for a total of 25 subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PTC299 | Experimental | Drug: PTC299PTC299 administered at 100 mg/dose twice per day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥18 years
- Diagnosis of NF2
- Presence of vestibular schwannomas
- Evidence of progressive increase in vestibular schwannoma size or worsening hearing loss due to vestibular schwannoma
- Adequate functional status (Karnofsky Performance Score ≥60)
Key exclusion criteria (2 listed)
- Uncontrolled hypertension, major bleeding, HIV infection, or recent acute cardiovascular event
- Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)
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 |
|---|---|---|
| PTC299PTC299 will be administered orally at 100 mg/dose twice per day for up to 1 year or until tumor progression | Drug | PTC299 |
Primary outcome
To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2.
Time frame: 48 weeks
7 secondary outcomes
To assess the effects of PTC299 on pure tone thresholds, brainstem auditory evoked responses (BAERs), and otoacoustic emissions (OAEs) in patients with NF2
Time frame: 48 weeks
To determine if PTC299 alters the perception of tinnitus
Time frame: 48 weeks
To evaluate the effects of PTC299 on tumor blood flow
Time frame: 48 weeks
To assess the effects of PTC299 on concentrations of circulating angiogenic factors or cytokines
Time frame: 48 weeks
To describe the PTC299 safety profile
Time frame: 48 weeks
To evaluate compliance with PTC299 treatment
Time frame: 48 weeks
To assess PTC299 plasma exposure over time
Time frame: 48 weeks
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2019.
- PTC Therapeutics websiteLink provided by the sponsor.
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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.
Jay Barth, MD principal investigator
PTC Therapeutics
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 PTC299 in people with Neurofibromatosis 2, run by PTC Therapeutics 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 11 inclusion and 2 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 12 Apr 2019. 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. 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?
To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2019.