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

Primary Purpose

Neurofibromatosis Type 1, Precancerous Condition

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
pirfenidone
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Neurofibromatosis Type 1 focused on measuring plexiform neurofibroma, neurofibromatosis type 1

Eligibility Criteria

3 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham Comprehensive Cancer Center
  • Children's National Medical Center
  • Children's Memorial Hospital - Chicago
  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
  • Mayo Clinic Cancer Center
  • Washington University School of Medicine
  • Beth Israel Medical Center - Singer Division
  • University Hospital at State University of New York - Upstate Medical University
  • Cleveland Clinic Taussig Cancer Center
  • Cancer Institute at Oregon Health and Science University
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Texas Children's Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
February 5, 2003
Last Updated
April 29, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00053937
Brief Title
Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas
Official Title
Phase I Trial Of Pirfenidone In Children With Neurofibromatosis Type 1 And Plexiform Neurofibromas
Study Type
Interventional

2. Study Status

Record Verification Date
April 2004
Overall Recruitment Status
Completed
Study Start Date
December 2002 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis Type 1, Precancerous Condition
Keywords
plexiform neurofibroma, neurofibromatosis type 1

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Masking
None (Open Label)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
pirfenidone

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte C. Widemann, MD
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham Comprehensive Cancer Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2970
Country
United States
Facility Name
Children's Memorial Hospital - Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Mayo Clinic Cancer Center
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Beth Israel Medical Center - Singer Division
City
New York
State/Province
New York
ZIP/Postal Code
10128
Country
United States
Facility Name
University Hospital at State University of New York - Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Cancer Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Texas Children's Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-2399
Country
United States

12. IPD Sharing Statement

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

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