At a glance
ClinicalIndex Comparison Record- ✓Age 3-21 years with body surface area ≥0.31 m²
- ✓Diagnosis of NF1 with progressive plexiform neurofibromas meeting NIH criteria, potentially causing significant morbidity (airway/vessel compromise, nerve compression, deformity, hypertrophy, pain)
- ✓At least one other NF1 diagnostic criterion besides plexiform neurofibroma (e.g., ≥6 café-au-lait spots, freckling, optic glioma, Lisch nodules, bony lesions, or first-degree relative with NF1)
- ✓Measurable plexiform neurofibroma ≥3 cm in one dimension with documented progression: ≥20% volume increase, ≥13% increase in product of two longest perpendicular diameters, or ≥6% increase in longest diameter over two consecutive scans or ~1 year
- ✕Pregnant or breastfeeding females
- ✕Clinically significant unrelated systemic illness (serious infections, significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise ability to tolerate pirfenidone or interfere with study procedures or results
- ✕Ongoing radiation, chemotherapy, hormonal therapy, immunotherapy, or biologic therapy directed at the tumor
- ✕Prior treatment with pirfenidone
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Phase II Trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
In Brief
A Phase 2 clinical trial evaluating Pirfenidone for Neurofibromatosis 1 and Neurofibroma, Plexiform. Completed, enrolled 36 participants across 15 sites.
Detailed 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)
Study Details
Timeline
Interventions
Pirfenidone orally as capsules three times a day approximately every 8 hours for cycles of 28 days with no rest period between cycles (28 day treatment cycles); 500 mg/m\^2 every 8 hours (1500 mg/m2/day).