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Pirfenidone in Treating Young Patients With Neurofibromatosis Type I and Recurrent or Progressive Plexiform Neurofibromas
This study is ongoing, but not recruiting participants.
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00078936
  Purpose

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 progressive plexiform neurofibroma.


Condition Intervention Phase
Neurofibromatosis Type 1 (nf1)
Precancerous/Nonmalignant Condition
Drug: pirfenidone
Phase II

Genetics Home Reference related topics: familial encephalopathy with neuroserpin inclusion bodies neurofibromatosis type 1 neurofibromatosis type 2
MedlinePlus related topics: Cancer Neurofibromatosis
Drug Information available for: Pirfenidone
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Trial Of Pirfenidone In Children, Adolescents, And Young Adults With Neurofibromatosis Type I And Progressive Plexiform Neurofibromas

Further study details as provided by National Cancer Institute (NCI):

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

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

Estimated Enrollment: 36
Study Start Date: October 2005
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00078936

Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New York
Beth Israel Medical Center - Singer Division
New York, New York, United States, 10028
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399
Sponsors and Collaborators
Investigators
Principal Investigator: Brigitte C. Widemann, MD NCI - Pediatric Oncology Branch
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000353200, NCI-04-C-0080
Study First Received: March 8, 2004
Last Updated: January 14, 2009
ClinicalTrials.gov Identifier: NCT00078936  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
neurofibromatosis type 1 (NF1)
plexiform neurofibroma

Study placed in the following topic categories:
Precancerous Conditions
Neurodegenerative Diseases
Neurofibromatosis type 1
Neurofibromatosis 1
Recurrence
Pirfenidone
Heredodegenerative Disorders, Nervous System
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Neurofibroma
Neuromuscular Diseases
Peripheral Nervous System Diseases
Neurofibromatoses
Peripheral Nervous System Neoplasms
Neurofibroma, Plexiform
Nerve Sheath Neoplasms
Nervous System Neoplasms
Neurocutaneous Syndromes

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Antineoplastic Agents
Neoplasms, Nerve Tissue
Nervous System Diseases
Physiological Effects of Drugs
Pharmacologic Actions
Neoplasms
Sensory System Agents
Analgesics, Non-Narcotic
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009