PTC299 for Treatment of Neurofibromatosis Type 2

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

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.

Study Overview

• Status: Terminated
• Conditions: Neurofibromatosis 2
• Intervention / Treatment: Drug: PTC299

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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
To evaluate compliance with PTC299 treatment	48 weeks
To assess PTC299 plasma exposure over time	48 weeks

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Collaborators: United States Department of Defense

Publications and helpful links

Helpful Links

• PTC Therapeutics website

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 31, 2009
• Primary Completion (ACTUAL): March 31, 2012
• Study Completion (ACTUAL): March 31, 2012

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (ESTIMATE): June 1, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: VEGF; Angiogenesis; Neurofibromatosis; Post-transcriptional control; PTC299
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Neurodegenerative Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Ear Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Cranial Nerve Diseases; Neuroendocrine Tumors; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Cranial Nerve Neoplasms; Neuroma, Acoustic; Neurilemmoma; Neuroma; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Neurofibromatosis 2
• Other Study ID Numbers: PTC299-ONC-007-NF2; NF080100