Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas

Completed · Phase 2

Conditions studied: Neurofibromatosis 1, Neurofibroma, Plexiform

In brief

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)

Key facts

Study ID

NCT00076102

Run by

National Cancer Institute (NCI)

People needed

36

Starts

2004-07-21

Expected to finish

2010-04-01

Last updated by the study team

2018-04-23

Who can join

Age: 3 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Pregnant or breast feeding females are excluded, because the toxic effects and pharmacology of pirfenidone in the fetus and newborn are unknown.
• Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), which in the judgment of the Principal or Associate Investigator would compromise the patient's ability to tolerate pirfenidone or are likely to interfere with the study procedures or results.
• An investigational agent within the past 30 days.
• Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy (for example interferon).
• Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.
• Prior treatment with pirfenidone.
• Evidence of an optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy

Where it is running

• University of Alabama — Birmingham, Alabama, United States
• Childrens National Medical Center — Washington D.C., District of Columbia, United States
• Childrens Memorial Hospital, Chicago — Chicago, Illinois, United States
• Johns Hopkins Oncology Center — Baltimore, Maryland, United States
• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States
• Childrens Hospital, Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• Mayo Clinic, Rochester — Rochester, Minnesota, United States
• St. Louis Children's Hospital — St Louis, Missouri, United States
• Beth Israel Medical Center — New York, New York, United States
• SUNY Upstate Medical University — Syracuse, New York, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Oregon Health Sciences University — Portland, Oregon, United States
• Childrens Hospital, Philadelphia — Philadelphia, Pennsylvania, United States
• Childrens Hospital, Pittsburgh — Pittsburgh, Pennsylvania, United States
• Texas Children's Hospital — Houston, Texas, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.