• Time to disease progression [ Designated as safety issue: No ]
  
• Objective response rate [ Designated as safety issue: No ]
  
• Toxicity [ Designated as safety issue: Yes ]
  

• Quality of life [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the time to disease progression in pediatric patients with neurofibromatosis type 1 (NF1) and recurrent or progressive plexiform neurofibroma treated with pirfenidone.
• Determine the objective response rate in patients treated with this drug.
• Determine the toxicity of this drug in these patients.

Secondary

• Determine the quality of life of patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral pirfenidone three times daily continuously for a course of 28 days. Courses repeat in the absence of disease progression or unacceptable toxicity.

For patients 6 to 18 years of age, quality of life is assessed at baseline, before courses 4 and 7, and then after every 6 courses.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 12-14 months.

DISEASE CHARACTERISTICS:

• All of the following:

  • Diagnosis of neurofibromatosis type 1 (NF1)

  • Histologically confirmed OR consistent clinical and radiographic findings of plexiform neurofibroma (defined as neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches)

    • Recurrent disease (presence of new lesion) or progressive disease as documented on last 2 consecutive MRI or CT scans or within the past year by 1 of the following:

      • At least 20% increase in volume
      • At least 13% increase in the product of the 2 longest perpendicular diameters
      • At least 6% increase in the longest diameter
    • Measurable lesion at least 3 cm in 1 dimension

  • Meets 1 or more of the following other diagnostic criteria for NF1:

    • At least 6 cafe-au-lait spots

      • At least 0.5 cm in prepubertal patients
      • At least 1.5 cm in postpubertal patients
    • Freckling in the axilla or groin
    • Optic glioma
    • At least 2 Lisch nodules

    • One of the following distinctive bony lesions:

      • Dysplasia of the sphenoid bone
      • Dysplasia of the long bone cortex
      • Thinning of the long bone cortex
    • One first-degree relative with NF1

• Ineligible for or refused complete resection of plexiform neurofibroma

  • Prior surgery for progressive disease allowed provided the plexiform neurofibroma was incompletely resected and is measurable
• No evidence of malignant glioma or malignant peripheral nerve sheath tumor

PATIENT CHARACTERISTICS:

Age

• 3 to 21

Performance status

• Karnofsky 50-100% (over 10 years of age) OR
• Lansky 50-100% (10 years of age and under)

Life expectancy

• At least 12 months

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3*
• Hemoglobin ≥ 9 g/dL*
• Platelet count ≥ 150,000/mm^3* NOTE: *Transfusion independent

Hepatic

• Bilirubin normal (except for patients with Gilbert's syndrome)
• SGPT ≤ 2 times upper limit of normal
• No significant hepatic dysfunction

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 70 mL/min

Cardiovascular

• No significant cardiac dysfunction

Pulmonary

• No significant pulmonary dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study treatment
• Able to take pirfenidone by mouth
• Able to undergo MRI
• No clinically significant unrelated systemic illness that would preclude study participation
• No serious infection
• No other significant organ dysfunction
• No other cancer requiring treatment with chemotherapy or radiotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 1 week since prior filgrastim (G-CSF)
• No prior pirfenidone
• No concurrent immunotherapy
• No concurrent biologic therapy (e.g., interferon)
• No concurrent hematopoietic growth factors

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• Concurrent corticosteroids allowed
• No concurrent hormonal therapy directed at the tumor

Radiotherapy

• At least 6 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Recovered from prior therapy (toxicity level less than grade 2)
• More than 30 days since prior investigational agents
• No other concurrent investigational agents