Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
Status:
Completed
Trial end date:
2010-04-01
Target enrollment:
Participant gender:
Summary
Background:
Neurofibromatosis Type 1 (NF1) is an autosomal dominant, progressive genetic disorder
characterized by diverse clinical manifestations. Patients with NF1 have an increased risk of
developing tumors of the central and peripheral nervous system including plexiform
neurofibromas, which are benign nerve sheath tumors that may cause severe morbidity and
possible mortality. The histopathology of these tumors suggests that events connected with
formation of fibroblasts might constitute a point of molecular vulnerability. Gene profile
analysis demonstrates overexpression of fibroblast growth factor, epidermal growth factor,
and platelet-derived growth factor in plexiform neurofibromas in patients with NF1.
Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors.
Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of
fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults
with progressive plexiform neurofibromas. A phase I trial of pirfenidone in children and
young adults with NF1 and plexiform neurofibromas was completed, and has established the
phase II dose (the dose resulting in a mean drug exposure [AUC] not more than 1 standard
deviation below the mean drug exposure [AUC] in adults who received pirfenidone at the dose
level demonstrating activity in fibrosing conditions). Pirfenidone has been well tolerated.
Objectives:
To determine whether pirfenidone increases the time to disease progression based on
volumetric measurements in children and young adults with NF1 and growing plexiform
neurofibromas.
To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas.
To describe and define the toxicities of pirfenidone.
Eligibility:
Individuals (greater than or equal to 3 years to less than or equal to 21 years of age) with
a clinical diagnosis of NF1 and inoperable, measurable, and progressive plexiform
neurofibromas that have the potential to cause substantial morbidity.
Design:
The phase II dose will be used in a single stage, single arm phase II trial The natural
history of the growth of plexiform neurofibromas is unknown. For this reason, time to disease
progression on the placebo arm of an ongoing National Cancer Institute (NCI) Pediatric
Oncology Branch (POB) placebo-controlled, double-blind, cross-over phase II trial of the
farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive
plexiform neurofibromas.
Funding source - Food and Drug Administration (FDA) Office of Orphan Products Development
(OOPD)