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

Unspecified Childhood Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00253474
• Other study ID #: 050232
• Secondary ID: 05-C-0232NCI-P66
• Status: Completed
• Phase: Phase 1
• First received: November 11, 2005
• Last updated: March 28, 2012
• Start date: September 2005
• Est. completion date: January 2011

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00156754

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm of Uncertain Malignant Potential
• Neurofibroma
• Neurofibroma, Plexiform
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Biological:
• PEG-interferon alfa-2a

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation