NCT00911248

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.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
11

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2009

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 28, 2009

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 1, 2009

Completed
2 months until next milestone

Study Start

First participant enrolled

July 31, 2009

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 31, 2012

Completed
Last Updated

April 12, 2019

Status Verified

April 1, 2019

Enrollment Period

2.7 years

First QC Date

May 28, 2009

Last Update Submit

April 9, 2019

Conditions

Neurofibromatosis 2

Keywords

AngiogenesisNeurofibromatosisPost-transcriptional controlPTC299VEGF

Outcome Measures

Primary Outcomes (1)

  • To assess the effects of PTC299 on tumor volume and/or word recognition in patients with NF2.

    48 weeks

Secondary Outcomes (7)

  • To assess the effects of PTC299 on pure tone thresholds, brainstem auditory evoked responses (BAERs), and otoacoustic emissions (OAEs) in patients with NF2

    48 weeks

  • To determine if PTC299 alters the perception of tinnitus

    48 weeks

  • To evaluate the effects of PTC299 on tumor blood flow

    48 weeks

  • To assess the effects of PTC299 on concentrations of circulating angiogenic factors or cytokines

    48 weeks

  • To describe the PTC299 safety profile

    48 weeks

  • +2 more secondary outcomes

Study Arms (1)

PTC299

EXPERIMENTAL

PTC299 administered at 100 mg/dose twice per day

Drug: PTC299

Interventions

PTC299DRUG

PTC299 will be administered orally at 100 mg/dose twice per day for up to 1 year or until tumor progression

PTC299

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Uncontrolled hypertension, major bleeding, HIV infection, or recent acute cardiovascular event
  • Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Links

MeSH Terms

Conditions

Neurofibromatosis 2Neurofibromatoses

Interventions

emvododstat

Condition Hierarchy (Ancestors)

Neuroma, AcousticNeurilemmomaNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeurofibromaNerve Sheath NeoplasmsNeoplasms, Nerve TissueNeuromaNeoplastic Syndromes, HereditaryVestibulocochlear Nerve DiseasesRetrocochlear DiseasesEar DiseasesOtorhinolaryngologic DiseasesOtorhinolaryngologic NeoplasmsCranial Nerve NeoplasmsCranial Nerve DiseasesNervous System DiseasesNeurocutaneous SyndromesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Jay Barth, MD

    PTC Therapeutics

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 28, 2009

First Posted

June 1, 2009

Study Start

July 31, 2009

Primary Completion

March 31, 2012

Study Completion

March 31, 2012

Last Updated

April 12, 2019

Record last verified: 2019-04

Locations

US(1)