Clinical Trial: PTC299 for Treatment of Neurofibromatosis Type 2

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Phase 2 Study to Assess the Efficacy, Safety, and Pharmacodynamic Activity of PTC299 in Patients With Neurofibromatosis Type 2

Brief 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. 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 Summary: 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.
Sponsor: PTC Therapeutics

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • To assess the effect of PTC299 on pure tone thresholds and brainstem auditory evoked responses (BAERs) and otoacoustic emissions (OAEs) in patients with NF2 [ Time Frame: 48 months ]
  • To determine if PTC299 alters the perception of tinnitus [ Time Frame: 48 months ]
  • 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 ]


Information By: PTC Therapeutics

Dates:
Date Received: May 28, 2009
Date Started: July 2009
Date Completion: May 2012
Last Updated: April 6, 2012
Last Verified: April 2012