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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00053937

Collaborator

(none)

Locations

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neurofibromatosis Type 1 Precancerous Condition	Drug: pirfenidone	Phase 1

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 Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Phase I Trial Of Pirfenidone In Children With Neurofibromatosis Type 1 And Plexiform Neurofibromas

Study Start Date :

Dec 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 21 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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