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

NCT ID: NCT00253474

Last Updated: 2012-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2011-01-31

Brief Summary

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.

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.

Conditions

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

Study Design

• Primary Study Purpose: TREATMENT

Interventions

PEG-interferon alfa-2a

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Brigitte C. Widemann, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Children's National Medical Center

Washington D.C., District of Columbia, United States

Children's Memorial Hospital - Chicago

Chicago, Illinois, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21242495 (View on PubMed)

Other Identifiers

05-C-0232

Identifier Type: -

Identifier Source: secondary_id

NCI-P6670

Identifier Type: -

Identifier Source: secondary_id

CDR0000448811

Identifier Type: -

Identifier Source: secondary_id

050232

Identifier Type: -

Identifier Source: org_study_id

NCT00156754

Identifier Type: -

Identifier Source: nct_alias