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PTC299 for Treatment of Neurofibromatosis Type 2

This study has suspended participant recruitment.
United States Department of Defense
Information provided by:
PTC Therapeutics Identifier:
First received: May 28, 2009
Last updated: April 6, 2012
Last verified: April 2012
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: 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

Resource links provided by NLM:

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:
  • To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2. [ Time Frame: 48 weeks ]

Secondary Outcome Measures:
  • 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 ]

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
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Please refer to this study by its identifier: NCT00911248

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
PTC Therapeutics
United States Department of Defense
Principal Investigator: Jay Barth, MD PTC Therapeutics
  More Information

Additional Information:
Responsible Party: Leslie Callahan, RN, MS, PTC Therapeutics, Inc. Identifier: NCT00911248     History of Changes
Other Study ID Numbers: PTC299-ONC-007-NF2
Study First Received: May 28, 2009
Last Updated: April 6, 2012

Keywords provided by PTC Therapeutics:
Post-transcriptional control

Additional relevant MeSH terms:
Neurofibromatosis 2
Nerve Sheath Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroma, Acoustic
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Vestibulocochlear Nerve Diseases
Retrocochlear Diseases
Ear Diseases
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Cranial Nerve Neoplasms
Cranial Nerve Diseases processed this record on April 28, 2017