A Phase II Study of Pegylated Interferon Alfa 2b (PEG-Intron(Trademark)) in Children With Diffuse Pontine Gliomas

Summary

Diffuse pontine gliomas are tumors on the pons portion of the brainstem. Their peak incidence is in children between 5 and 10 years old. Their location makes surgical resection impossible. Most patients are treated with radiation, which typically delays progression of the tumor for a median time of only about 6 months; median survival time is less than 1 year. The addition of chemotherapy has not improved the outcome.

Alpha, beta, and gamma interferons have been used to treat malignant brain tumors, with mixed results. Different doses and different methods of administration have been studied. Alpha interferon is usually given in high doses 2 or 3 times a week, but it has serious side effects at these doses. Recent studies have shown that administering chemotherapy more frequently at smaller doses (metronomic) may have a better effect against the tumor.

PEG-Intron(Trademark) is a form of interferon alpha combined with monomethoxy polyethylene glycol (PEG). It has a longer half-life than interferon alone, is administered once a week, and the long half-life reduces the peaks and troughs in blood levels.

This study will enroll 32 patients under age 21. The primary goals of the study are to determine if there is a difference in the 2-year survival rate of patients treated with radiation alone and those treated with radiation followed by PEG-Intron(Trademark) and to define the toxicities of PEG-Intron(Trademark) in the study doses. Secondary goals are to evaluate various magnetic resonance imaging (MRI) techniques for noninvasive monitoring of changes in the brainstem and to evaluate neuropsychological function.

In this study, PEG-Intron(Trademark) will be administered subcutaneously once a week at low doses (0.3 microgram per kilogram of body weight) for a 4-week cycle. The cycles will be repeated indefinitely until progression of disease or serious side effects develop. For less severe effects, the dose will be lowered and the patient may remain in the study. For more severe effects, the dose will be discontinued. Patients in the study may receive supportive medication but may not receive other forms of chemotherapy.

Patients or their caregivers will be instructed in how to inject the drug. Patients and/or caregivers will be asked to maintain a diary documenting the dose, site of administration, and any side effects. The diary will be reviewed at each National Cancer Institute (NCI) visit. Patients will return to NCI before cycles 2 and 3. If there are no significant side effects, patients may then return to NCI before every other cycle, indefinitely (i.e., before cycles 5, 7, 9, etc.).

Patients will undergo the following tests and procedures:

* Physical examination, including neurologic exam, monthly
* Complete blood count, differential, and platelet count weekly during cycle 1 and every 2 weeks thereafter if no severe side effects occur
* Blood chemistries weekly during cycle 1 and every 2 weeks thereafter if no severe side effects occur
* Endocrine function tests before each cycle
* Urinalysis before each cycle
* MRI of the brain before cycles 1, 2, 3, 5, 7, and every other month; patients may also have proton magnetic spectroscopic imaging performed at the time of the MRI

Conditions

• Diffuse Intrinsic Pontine Glioma

Interventions

PROCEDURE

adjuvant therapy

BIOLOGICAL

pegylated interferon alfa

0.3 mg/kg subcutaneously once a week for 4 weeks beginning 2-10 weeks after completion of radiation therapy and continued until disease progression or one of the other off study criteria.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Kathy Warren, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-05-31

Primary Completion

2010-12-31

Completion

2012-01-31

Countries

• United States

Study Locations