Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Pirfenidone may slow the growth or prevent further development of plexiform neurofibromas. PURPOSE: Phase I trial to study the effectiveness of pirfenidone in treating young patients who have neurofibromatosis type 1 and plexiform neurofibroma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose or comparable dose of pirfenidone in pediatric patients with neurofibromatosis type 1 and inoperable, symptomatic plexiform neurofibromas. Determine the toxic effects of this drug in these patients. Determine the plasma pharmacokinetics of this drug in these patients. Determine, preliminarily, if this drug could be beneficial for pediatric patients with refractory solid tumors. Assess the quality of life of patients treated with this drug. OUTLINE: This is an open-label, multicenter, dose-escalation study. Patients receive oral pirfenidone three times daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of pirfenidone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Quality of life is assessed at baseline, before course 4, and then after every 6 courses. PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 18 months.

Official Title
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Phase I Trial Of Pirfenidone In Children With Neurofibromatosis Type 1 And Plexiform Neurofibromas

Conditions
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Neurofibromatosis Type 1, Precancerous Condition

Intervention / Treatment
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* Drug: pirfenidone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of neurofibromatosis type 1 (NF1) AND Plexiform neurofibromas Neurofibromas that have grown along the length of a nerve and may involve multiple fascicles and branches (spinal neurofibromas involve 2 or more levels with connection between the levels or extending laterally along the nerve) Potential to cause significant morbidity such as: Head and neck lesions that could compromise airway or great vessels Brachial or lumbar plexus lesions that could cause nerve compression and loss of function Lesions that could result in major deformity (e.g., orbital lesions) or significant cosmetic problems Lesions of the extremity that cause limb hypertrophy or loss of function Painful lesions Meets at least 1 other diagnostic criteria for NF1 6 or more cafe-au-lait spots (at least 0.5 cm in prepubertal patients or at least 1.5 cm in postpubertal patients) Freckling in the axilla or groin Optic glioma 2 or more Lisch nodules Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex) First-degree relative with NF1 Measurable plexiform neurofibromas At least 3 cm in 1 dimension Tumor resection not feasible No history of malignant peripheral nerve sheath tumor or other cancer No evidence of an active optic glioma requiring chemotherapy or radiotherapy No malignant glioma PATIENT CHARACTERISTICS: Age 3 to 21 Performance status Karnofsky 50-100% (over 10 years of age) Lansky 50-100% (10 years and under) Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Hemoglobin at least 9.0 g/dL Platelet count at least 150,000/mm^3 Hepatic Bilirubin normal SGPT no greater than 2 times upper limit of normal No clinically significant hepatic dysfunction that would preclude study participation Renal Creatinine normal for age OR Creatinine clearance at least 70 mL/min Cardiovascular No clinically significant cardiac dysfunction that would preclude study participation Pulmonary No clinically significant pulmonary dysfunction that would preclude study participation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 months after study Must be able to take pirfenidone orally No serious infections No clinically significant unrelated systemic illness or organ dysfunction that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy At least 30 days since prior immunotherapy No concurrent immunotherapy No concurrent hematopoietic growth factors Chemotherapy At least 30 days since prior chemotherapy No concurrent chemotherapy directed at the tumor Endocrine therapy At least 30 days since prior hormonal therapy directed at the tumor No concurrent hormonal therapy directed at the tumor Radiotherapy At least 90 days since prior radiotherapy to the site of the plexiform neurofibroma No concurrent radiotherapy directed at the tumor Surgery Not specified Other Recovered from prior therapy More than 30 days since prior investigational agents No prior pirfenidone No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pirfenidone|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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plexiform neurofibroma, neurofibromatosis type 1