RATIONALE: Some tumors need growth factors produced by the body's white blood cells to keep growing. Pirfenidone may interfere with growth factors and stop the tumor from growing.

PURPOSE: Phase II trial to study the effectiveness of pirfenidone in treating young patients who have neurofibromatosis type 1 and recurrent or progressiveplexiform neurofibroma.

Condition	Treatment or Intervention	Phase
neurofibromatosis 1 and 2 (NF1 and NF2)	Drug: pirfenidone  Procedure: anti-cytokine therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

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 on days 1-28. Courses repeat every 28 days 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 course 4, and then after every 6 courses.

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

Ages Eligible for Study:  3 Years   -   21 Years,  Genders Eligible for Study:  Both

Criteria

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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3300,  United States
District of Columbia
      Children's National Medical Center, Washington,  District of Columbia,  20010-2970,  United States
Illinois
      Children's Memorial Hospital - Chicago, Chicago,  Illinois,  60614,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231,  United States
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Missouri
      St. Louis Children's Hospital, Saint Louis,  Missouri,  63110,  United States
New York
      Beth Israel Medical Center - Singer Division, New York,  New York,  10128,  United States
      University Hospital at State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States
      Children's Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
Texas
      Texas Children's Cancer Center, Houston,  Texas,  77030-2399,  United States

Study chairs or principal investigators

Brigitte C. Widemann, MD,  Principal Investigator,  Pediatric Oncology Branch   

Study ID Numbers:  CDR0000353200; NCI-04-C-0080
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00078936
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08