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

A Phase I Trial of Peginterferon Alfa-2b (PEG-Intron) for Plexiform Neurofibromas

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Childhood Solid Tumor, Protocol Specific; Neoplasm of Uncertain Malignant Potential
• Intervention / Treatment: Biological: PEG-interferon alfa-2a

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
  • Maryland
    • Bethesda, Maryland, United States, 20892-1182
      • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Jakacki RI, Dombi E, Potter DM, Goldman S, Allen JC, Pollack IF, Widemann BC. Phase I trial of pegylated interferon-alpha-2b in young patients with plexiform neurofibromas. Neurology. 2011 Jan 18;76(3):265-72. doi: 10.1212/WNL.0b013e318207b031.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: November 11, 2005
• First Submitted That Met QC Criteria: November 11, 2005
• First Posted (Estimate): November 15, 2005

Study Record Updates

• Last Update Posted (Estimate): March 29, 2012
• Last Update Submitted That Met QC Criteria: March 28, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; neoplasm of uncertain malignant potential
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neuromuscular Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Neurofibroma; Neurofibroma, Plexiform; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: 050232; 05-C-0232; NCI-P6670; CDR0000448811