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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Last refreshed on: 12 December 2020
Main ID:  NCT00076102
Date of registration: 13/01/2004
Prospective Registration: Yes
Primary sponsor: National Cancer Institute (NCI)
Public title: Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
Scientific title: Phase II Trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
Date of first enrolment: July 21, 2004
Target sample size: 36
Recruitment status: Completed
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     Brigitte C Widemann, M.D.
Affiliation:  National Cancer Institute, National Institutes of Health
Key inclusion & exclusion criteria


1. Age: greater than or equal to 3 years and Less than or equal to 21 years of age.
Required body surface area (BSA): greater than or equal to 0.31 m^2.

2. Diagnosis: Patients with NF1 and progressive plexiform neurofibromas that have
the potential to cause significant morbidity, such as (but not limited to) head
and neck lesions that could compromise the 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, and painful lesions. Histologic confirmation of
tumor is not necessary in the presence of consistent clinical and radiographic
findings, but should be considered if malignant degeneration of a plexiform
neurofibroma is clinically suspected. In addition to plexiform neurofibroma(s),
all study subjects must have at least one other diagnostic criteria for NF1
listed below (National Institutes of Health (NIH) Consensus Conference):

1. Six or more cafe-au-lait spots (greater than or equal to 0.5 cm in prepubertal
subjects or greater than or equal to 1.5 cm in postpubertal subjects)

2. Freckling in the axilla or groin

3. Optic glioma

4. Two or more Lisch nodules

5. A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or
thinning of long bone cortex)

6. A first-degree relative with NF1

In this study a plexiform neurofibroma is defined as a neurofibroma that has grown along
the length of a nerve and may involve multiple fascicles and branches. A spinal plexiform
neurofibroma involves two or more levels with connection between the levels or extending
laterally along the nerve.

3. Measurable disease: Patients must have measurable plexiform neurofibroma(s). For the
purpose of this study a measurable lesion will be defined as a lesion of at least 3 cm
measured in one dimension. There must be evidence of recurrent or progressive disease as
documented by an increase in size or the presence of new plexiform neurofibromas on MRI.
Progression at the time of study entry is defined as:

A. A measurable increase of the plexiform neurofibroma (greater than or equal to 20%
increase in the volume, or a greater than or equal to 13% increase in the product of the
two longest perpendicular diameters, or a greater than or equal to 6% increase in the
longest diameter) over the last two consecutive scans (magnetic resonance imaging (MRI) or
computed tomography (CT), or over the time period of approximately one year prior to
evaluation for this study.

B. Patients who underwent surgery for a progressive plexiform neurofibroma will be eligible
to enter the study after the surgery, provided the plexiform neurofibroma was incompletely
resected and is measurable.

4. Prior therapy: Patients with NFI are eligible at the time of recurrence or progression
of an inoperable plexiform neurofibroma. Patients will only be eligible if complete tumor
resection is not feasible, or if a patient with a surgical option refuses surgery.

Since there is no standard effective chemotherapy for patients with NF1 and progressive
plexiform neurofibromas, patients may be treated on this trial without having received
prior medical therapy.

Patients who received prior medical treatment for their plexiform neurofibroma(s) must have
recovered from the toxic effects of all prior therapy before entering this study. The
Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE-3)
Version 3.0 will be used for toxicity assessment. A copy of the CTCAE version 3.0 can be
downloaded from the CTEP home page (http:// Recovery is defined as a
toxicity grade less than 2, unless otherwise specified in the Inclusion and Exclusion

Patients must have had their last dose of radiation therapy at least six weeks prior to
study entry, and their last dose of chemotherapy at least four weeks prior to study entry.
Patients who received G-CSF after the prior cycle of chemotherapy must be off G-CSF for at
least one week prior to entering this study.

5. Performance Status: Performance Status: Patients should have a life expectancy of at
least 12 months. Patients greater than 10 years must have a Karnofsky performance level
greater than or equal to 50, and children less than or equal to 10 years must have a Lansky
performance level greater than or equal to 50. Patients who are wheelchair bound because of
paralysis should be considered ambulatory when they are up in their wheel chair.

6. Hematologic Function: Patients must have an absolute granulocyte count greater than or
equal to 1,500/uL, a hemoglobin greater than or equal to 9.0 gm/dl, and a platelet count
greater than or equal to 150,000/microliter at study entry (all transfusion independent).

7. Hepatic Function: Patients must have a bilirubin within normal limits and serum glutamic
pyruvic transaminase (SGPT) less then or equal to 2x upper limit of normal. Patients with
Gilbert syndrome are excluded from the requirement of a normal bilirubin. (Gilbert syndrome
is found in 3-10% of the general population, and is characterized by mild, chronic
unconjugated hyperbilirubinemia in the absence of liver disease or overt hemolysis).

8. Renal Function: Patients must have an age-adjusted normal serum creatinine (see table
below) OR a creatinine clearance greater than or equal to 70 mL/min/1.73 m^2.

Age Maximum Serum Creatinine

(years) (mg/dl)

less than or equal to 5 0.8

5 less than age less than or equal to 10 1.0

10 less than age less than or equal to 15 1.2

greater than 15 1.5

9. Informed Consent: All patients or their legal guardians (if the patients is less than 18
years old) must sign an Institutional Review Board (IRB) approved document of informed
consent (screening protocol) prior to performing studies to determine patient eligibility.
After confirmation of patient eligibility all patients or their legal guardians must sign
the protocol specific informed consent to document their understanding of the
investigational nature and the risks of this study before any protocol related studies are
performed (other than the studies which were performed to determine patient eligibility).
When appropriate, pediatric patients will be included in all discussions. Age appropriate
assent forms for children from 7 through 12 years, and for children from 13 through 17
years have been developed and will be signed by the pediatric patients, when appropriate,
in order to obtain writt

Age minimum: 3 Years
Age maximum: 21 Years
Gender: All
Health Condition(s) or Problem(s) studied
Neurofibroma, Plexiform
Neurofibromatosis 1
Drug: Pirfenidone
Primary Outcome(s)
Median Time to Disease Progression [Time Frame: 5 years]
Number of Participants With Adverse Events [Time Frame: 5 years]
Percentage of Participants Who Had an Objective Response Rate [Time Frame: =4 weeks]
Secondary Outcome(s)
Longitudinal Total Quality of Life Scores Assessed by the Impact of Pediatric Illness Scale [Time Frame: prior to cycles 1, 4, 7 and 10.]
Number of Participants Who Contributed to the Tissue Bank [Time Frame: 5 years]
Number of Participants With A Response Evaluation Determined by the Comparison of One-Dimensional (1D) Magnetic Resonance Imaging [Time Frame: Prior to cycles 1, 4, 7, and 10 and then every 6 cycles thereafter until progression]
Number of Participants With A Response Evaluation Determined by the Comparison of Three-Dimensional (3D) Magnetic Resonance Imaging [Time Frame: Prior to cycles 1, 4, 7, and 10 and then every 6 cycles thereafter, approximately 5 years]
Number of Participants With A Response Evaluation Determined by the Comparison of Two-Dimensional (2D) Magnetic Resonance Imaging [Time Frame: Prior to cycles 1, 4, 7, and 10 and then every 6 cycles thereafter until progression]
Quality of Life (QOL) Using the Impact of Pediatric Illness (IPI) Scale at Baseline [Time Frame: Baseline]
Secondary ID(s)
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results available: Yes
Date Posted: 12/07/2012
Date Completed:
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