Phase I Study of Pirfenidone in Pediatric Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Trial Contact Information Registry Information
Alternate Title
Pirfenidone in Treating Young Patients With Neurofibromatosis Type 1 and Plexiform Neurofibromas
Basic Trial Information
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Status
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Age
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Protocol IDs
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Phase I
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Prevention
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Completed
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3 to 21
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NCI
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NCI-03-C-0058A NCT00053937
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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.
Entry 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
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 Other - Recovered from prior therapy
- More than 30 days since prior investigational agents
- No prior pirfenidone
- No other concurrent investigational agents
Patient Characteristics:
Age Performance status - Karnofsky 50-100% (over 10 years of age)
- Lansky 50-100% (10 years and under)
Life expectancy Hematopoietic - Absolute granulocyte count at least 1,500/mm3
- Hemoglobin at least 9.0 g/dL
- Platelet count at least 150,000/mm3
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
Expected Enrollment A total of 3-18 patients will be accrued for this study within 18 months. 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.
Trial Contact Information
Trial Lead Organizations NCI - Center for Cancer Research-Medical Oncology | | | Brigitte Widemann, MD, Protocol chair | | | |
Registry Information | | Official Title | | Phase I Trial Of Pirfenidone In Children With Neurofibromatosis Type 1 And Plexiform Neurofibromas | | Trial Start Date | | 2002-12-10 | | Registered in ClinicalTrials.gov | | NCT00053937 | | Date Submitted to PDQ | | 2002-12-10 | | Information Last Verified | | 2004-04-30 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |