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PTC299 for Treatment of Neurofibromatosis Type 2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00911248
Recruitment Status : Terminated
First Posted : June 1, 2009
Last Update Posted : April 12, 2019
United States Department of Defense
Information provided by (Responsible Party):
PTC Therapeutics

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.

Condition or disease Intervention/treatment Phase
Neurofibromatosis 2 Drug: PTC299 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : July 31, 2009
Actual Primary Completion Date : March 31, 2012
Actual Study Completion Date : March 31, 2012

Arm Intervention/treatment
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

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

Secondary Outcome Measures :
  1. 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 ]
  2. To determine if PTC299 alters the perception of tinnitus [ Time Frame: 48 weeks ]
  3. To evaluate the effects of PTC299 on tumor blood flow [ Time Frame: 48 weeks ]
  4. To assess the effects of PTC299 on concentrations of circulating angiogenic factors or cytokines [ Time Frame: 48 weeks ]
  5. To describe the PTC299 safety profile [ Time Frame: 48 weeks ]
  6. To evaluate compliance with PTC299 treatment [ Time Frame: 48 weeks ]
  7. To assess PTC299 plasma exposure over time [ Time Frame: 48 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00911248

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
PTC Therapeutics
United States Department of Defense
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Principal Investigator: Jay Barth, MD PTC Therapeutics
Additional Information:
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Responsible Party: PTC Therapeutics
ClinicalTrials.gov Identifier: NCT00911248    
Other Study ID Numbers: PTC299-ONC-007-NF2
First Posted: June 1, 2009    Key Record Dates
Last Update Posted: April 12, 2019
Last Verified: April 2019
Keywords provided by PTC Therapeutics:
Post-transcriptional control
Additional relevant MeSH terms:
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Neurofibromatosis 1
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 Diseases
Neuromuscular Diseases
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
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