PTC299 for Treatment of Neurofibromatosis Type 2
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Neurofibromatosis 2 |
Drug: PTC299 |
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 Phase 2 Study to Assess the Efficacy, Safety, and Pharmacodynamic Activity of PTC299 in Patients With Neurofibromatosis Type 2 |
- To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To determine if PTC299 alters the perception of tinnitus [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To evaluate the effects of PTC299 on tumor blood flow [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To assess the effects of PTC299 on concentrations of circulating angiogenic factors or cytokines [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To describe the PTC299 safety profile [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- To evaluate compliance with PTC299 treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
- To assess PTC299 plasma exposure over time [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 25 |
| Study Start Date: | July 2009 |
| Estimated Study Completion Date: | May 2012 |
| Estimated Primary Completion Date: | May 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: PTC299
PTC299 administered at 100 mg/dose twice per day
|
Drug: PTC299
PTC299 will be administered orally at 100 mg/dose twice per day for up to 1 year or until tumor progression
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- Uncontrolled hypertension, major bleeding, HIV infection, or recent acute cardiovascular event
- Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)
Contacts and Locations| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| Principal Investigator: | Jay Barth, MD | PTC Therapeutics |
More Information
Additional Information:
No publications provided
| Responsible Party: | Leslie Callahan, RN, MS, PTC Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT00911248 History of Changes |
| Other Study ID Numbers: | PTC299-ONC-007-NF2, NF080100 |
| Study First Received: | May 28, 2009 |
| Last Updated: | April 6, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by PTC Therapeutics:
|
Angiogenesis Neurofibromatosis Post-transcriptional control PTC299 VEGF |
Additional relevant MeSH terms:
|
Neurofibromatosis 2 Neurofibromatoses Neuroma, Acoustic Neurilemmoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neurofibroma Nerve Sheath Neoplasms Neoplasms, Nerve Tissue Neuroma Nervous System Neoplasms |
Neoplasms by Site Neoplastic Syndromes, Hereditary Vestibulocochlear Nerve Diseases Retrocochlear Diseases Ear Diseases Otorhinolaryngologic Diseases Otorhinolaryngologic Neoplasms Cranial Nerve Neoplasms Cranial Nerve Diseases Nervous System Diseases Neurocutaneous Syndromes Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn |
ClinicalTrials.gov processed this record on May 16, 2013