Know Cancer

forgot password

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

Phase 1
3 Years
21 Years
Not Enrolling
Neurofibromatosis Type 1, Precancerous Condition

Thank you

Trial Information

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


- Determine the maximum tolerated dose or "comparable dose" of pirfenidone in pediatric
patients with neurofibromatosis type 1 and inoperable, symptomatic plexiform

- 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.

Inclusion Criteria


- 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


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Prevention

Principal Investigator

Brigitte C. Widemann, MD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

December 2002

Completion Date:

Related Keywords:

  • Neurofibromatosis Type 1
  • Precancerous Condition
  • plexiform neurofibroma
  • neurofibromatosis type 1
  • Neurofibroma
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Precancerous Conditions
  • Neurofibroma, Plexiform



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Mayo Clinic Cancer Center Rochester, Minnesota  55905
Washington University School of Medicine Saint Louis, Missouri  63110
University of Alabama at Birmingham Comprehensive Cancer Center Birmingham, Alabama  35294-3300
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
Children's National Medical Center Washington, District of Columbia  20010-2970
Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania  15213
Children's Memorial Hospital - Chicago Chicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
Texas Children's Cancer Center Houston, Texas  77030-2399
Cancer Institute at Oregon Health and Science University Portland, Oregon  97201-3098
University Hospital at State University of New York - Upstate Medical University Syracuse, New York  13210
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support Bethesda, Maryland  20892-1182
Beth Israel Medical Center - Singer Division New York, New York  10128