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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00053937
Recruitment Status : Completed
First Posted : February 6, 2003
Last Update Posted : April 30, 2015
Information provided by:
National Cancer Institute (NCI)

February 5, 2003
February 6, 2003
April 30, 2015
December 2002
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Complete list of historical versions of study NCT00053937 on Archive Site
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Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas
Phase I Trial Of Pirfenidone In Children With Neurofibromatosis Type 1 And Plexiform Neurofibromas

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.


  • 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.

Phase 1
Masking: None (Open Label)
Primary Purpose: Prevention
  • Neurofibromatosis Type 1
  • Precancerous Condition
Drug: pirfenidone
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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  • 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



  • 3 to 21

Performance status

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

Life expectancy

  • Not specified


  • Absolute granulocyte count at least 1,500/mm^3
  • Hemoglobin at least 9.0 g/dL
  • Platelet count at least 150,000/mm^3


  • Bilirubin normal
  • SGPT no greater than 2 times upper limit of normal
  • No clinically significant hepatic dysfunction that would preclude study participation


  • Creatinine normal for age OR
  • Creatinine clearance at least 70 mL/min


  • No clinically significant cardiac dysfunction that would preclude study participation


  • No clinically significant pulmonary dysfunction that would preclude study participation


  • 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


Biologic therapy

  • At least 30 days since prior immunotherapy
  • No concurrent immunotherapy
  • No concurrent hematopoietic growth factors


  • 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


  • At least 90 days since prior radiotherapy to the site of the plexiform neurofibroma
  • No concurrent radiotherapy directed at the tumor


  • Not specified


  • Recovered from prior therapy
  • More than 30 days since prior investigational agents
  • No prior pirfenidone
  • No other concurrent investigational agents
Sexes Eligible for Study: All
3 Years to 21 Years   (Child, Adult)
Contact information is only displayed when the study is recruiting subjects
United States
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National Cancer Institute (NCI)
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Study Chair: Brigitte C. Widemann, MD National Cancer Institute (NCI)
National Cancer Institute (NCI)
April 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP