PEG-Interferon Alfa-2b in Treating Young Patients With Plexiform Neurofibroma

National Institutes of Health Clinical Center (CC)

Status and phase: Completed; Phase 1

Conditions: Neoplasm of Uncertain Malignant Potential; Unspecified Childhood Solid Tumor, Protocol Specific

Treatments: Biological: PEG-interferon alfa-2a

Study type: Interventional

Funder types: NIH

Identifiers

NCT00253474

05-C-0232

050232

CDR0000448811

NCI-P6670

Details and patient eligibility

About

RATIONALE: PEG-interferon alfa-2b may interfere with the growth of tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PEG-interferon alfa-2b in treating young patients with plexiform neurofibroma.

Full description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of PEG-interferon alfa-2b in patients with unresectable plexiform neurofibroma. (Dose escalation portion of study closed to accrual as of 2/2005.)
• Determine the toxicity profile of this drug in these patients.

Secondary

• Obtain, preliminary, information about the efficacy of this drug in these patients.
• Evaluate the growth rate of plexiform neurofibroma using volumetric MRI analysis in patients treated with this drug.
• Evaluate the impact of this drug, in terms of "worst symptom" score, in these patients.

OUTLINE: This is a dose-escalation, multicenter study. (Dose-escalation portion of the study closed to accrual as of 2/2005.)

Patients receive PEG-interferon alfa-2b subcutaneously once weekly for 2 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of PEG-interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 6 patients experience dose-limiting toxicity. A total of 12 patients receive treatment at the MTD.

After completion of study treatment, patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Enrollment: 36 estimated patients

Sex: All

Ages: 1 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of plexiform neurofibroma which is progressive, symptomatic, or life threatening and for which there is no other standard medical management or surgical option

• Histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings provided the following are true:

  • No clinical observation or scan suggestive of malignant transformation

  • Meets ≥ 1 of the following diagnostic criteria for neurofibroma type 1 (NF1):

    • Six or more cafe-au-lait spots (> 0.5 cm in prepubertal patients or > 1.5 cm in post pubertal patients)
    • Freckling in axilla or groin
    • Optic glioma
    • Two or more Lisch nodules
    • A distinctive bony lesion (e.g., dysplasia of the sphenoid bone, dysplasia, or thinning of long bone cortex)
    • A first degree relative with NF1

• No history of malignant peripheral nerve sheath tumor

• No active visual pathway glioma

• No active brain tumor or brain metastases

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• At least 12 months

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Hemoglobin > 10 g/dL
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 1.5 mg/dL
• SGPT ≤ 2 times upper limit of normal
• No significant hepatic dysfunction

Renal

• Creatinine based on age as follows:

  • ≤ 0.8 mg/dL (for patients age 5 years and under)
  • ≤ 1.0 mg/dL (for patients age 6 to 10 years)
  • ≤ 1.2 mg/dL (for patients age 11 to 15 years)
  • ≤ 1.5 mg/dL (for patients age 16 to 21 years) OR

• Creatinine clearance ≥ 70 mL/min

Cardiovascular

• No significant cardiac dysfunction
• No severe cardiovascular disease
• No cardiac arrhythmia requiring chronic treatment
• No congestive heart failure
• No symptomatic ischemic heart disease

Pulmonary

• No significant pulmonary dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No serious infection
• No other significant unrelated systemic illness
• No significant organ dysfunction
• No other malignancy except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix
• No history of severe psychiatric condition or psychiatric disorder requiring hospitalization
• No history of suicidal ideation or attempt
• No thyroid dysfunction unresponsive to therapy
• No uncontrolled diabetes mellitus
• No history of HIV positivity
• No alcohol or drug abuse

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No concurrent colony-stimulating factors (e.g., erythropoietin or filgrastim [G-CSF])

Chemotherapy

• No concurrent chemotherapy for this disease

Endocrine therapy

• No concurrent chronic systemic corticosteroids
• No concurrent hormonal therapy for this disease

Radiotherapy

• No concurrent radiotherapy for this disease

Surgery

• Prior surgery allowed provided it has been at least 21 days since surgery and there is presence of residual tumor

Other

• Recovered from prior therapy
• More than 30 days since prior investigational agents