PTC299 for Treatment of Neurofibromatosis Type 2 - Full Text View

Sponsors and Collaborators:	PTC Therapeutics Department of Defense
Information provided by:	PTC Therapeutics
ClinicalTrials.gov Identifier:	NCT00911248

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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:

Genetics Home Reference related topics: neurofibromatosis type 1 neurofibromatosis type 2

MedlinePlus related topics: Cancer Neurofibromatosis

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]

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 ] [ 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 2011
Estimated Primary Completion Date:	May 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
PTC299: Experimental 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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00911248

Contacts

Contact: Diane M Goetz

(908) 912-9256

dgoetz@ptcbio.com

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Scott Plotkin, MD 617-724-8770

Sponsors and Collaborators

PTC Therapeutics

Department of Defense

Investigators

Principal Investigator:

Langdon Miller, MD

PTC Therapeutics

More Information

Additional Information:

PTC Therapeutics website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	PTC Therapeutics, Inc. ( Harry Miao, MD, PhD )
Study ID Numbers:	PTC299-ONC-007-NF2, NF080100
Study First Received:	May 28, 2009
Last Updated:	July 10, 2009
ClinicalTrials.gov Identifier:	NCT00911248 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by PTC Therapeutics:

Angiogenesis
Neurofibromatosis
Post-transcriptional control
PTC299
VEGF

Study placed in the following topic categories:

Vestibulocochlear Nerve Diseases
Otorhinolaryngologic Neoplasms
Neuroma, Acoustic
Retrocochlear Diseases
Neurodegenerative Diseases
Ear Diseases
Neurofibromatosis 1
Neurofibromatosis 2
Heredodegenerative Disorders, Nervous System
Neuromuscular Diseases
Neurofibroma
Neurofibromatosis Type 1
Neurofibromatosis Type 2
Neoplasms, Germ Cell and Embryonal

Neuroepithelioma
Nervous System Neoplasms
Neurocutaneous Syndromes
Otorhinolaryngologic Diseases
Neurilemmoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neurofibromatoses
Neuroma
Nerve Sheath Neoplasms

Additional relevant MeSH terms:

Vestibulocochlear Nerve Diseases
Otorhinolaryngologic Neoplasms
Neuroma, Acoustic
Retrocochlear Diseases
Neoplasms, Nerve Tissue
Cranial Nerve Neoplasms
Neurodegenerative Diseases
Ear Diseases
Neurofibromatosis 1
Neurofibromatosis 2
Heredodegenerative Disorders, Nervous System
Neoplasms by Site
Neurofibroma
Neuromuscular Diseases
Neoplasms, Germ Cell and Embryonal

Nervous System Neoplasms
Neurocutaneous Syndromes
Otorhinolaryngologic Diseases
Neoplasms by Histologic Type
Nervous System Diseases
Neurilemmoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Peripheral Nervous System Diseases
Neurofibromatoses
Cranial Nerve Diseases
Neuroma

ClinicalTrials.gov processed this record on September 11, 2009