Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Pirfenidone in Treating Young Patients With Neurofibromatosis Type I and Recurrent or Progressive Plexiform Neurofibromas

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	3 to 21	NCI	NCI-04-C-0080 NCT00078936

Objectives

Primary

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

Secondary

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

Entry 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

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

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/mm³*
• Hemoglobin ≥ 9 g/dL*
• Platelet count ≥ 150,000/mm³*

 [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

Expected Enrollment

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

Outcomes

Time to disease progression
Objective response rate
Toxicity

Quality of life

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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Brigitte Widemann, MD, Principal investigator		Ph: 301-496-7387

Registry Information
Official Title		Phase II Trial Of Pirfenidone In Children, Adolescents, And Young Adults With Neurofibromatosis Type I And Progressive Plexiform Neurofibromas
Trial Start Date		2005-10-25
Registered in ClinicalTrials.gov		NCT00078936
Date Submitted to PDQ		2004-01-15
Information Last Verified		2009-01-13

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