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

April 29, 2015 updated by: National Cancer Institute (NCI)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • 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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 21 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

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

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

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

Renal

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

Cardiovascular

  • No clinically significant cardiac dysfunction that would preclude study participation

Pulmonary

  • No clinically significant pulmonary dysfunction that would preclude study participation

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • More than 30 days since prior investigational agents
  • No prior pirfenidone
  • No other concurrent investigational agents

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Masking: NONE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Study Registration Dates

First Submitted

February 5, 2003

First Submitted That Met QC Criteria

February 5, 2003

First Posted (ESTIMATE)

February 6, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

April 30, 2015

Last Update Submitted That Met QC Criteria

April 29, 2015

Last Verified

April 1, 2004

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000269598
  • NCI-03-C-0058A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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