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

Phase 2

Completed

Conditions: Diffuse Intrinsic Pontine Glioma

Interventions: Procedure: adjuvant therapy
Biological: pegylated interferon alfa

Registration Number: NCT00036569

Lead Sponsor: National Cancer Institute (NCI)

Brief 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

Detailed Description: Background:

Children with diffuse pontine gliomas have a dismal prognosis. Because surgery in this area is difficult, radiation therapy has been the mainstay of treatment. Although some children may improve clinically after radiation therapy, the effect is short-lived and almost all progress within several months. Chemotherapy has not had a significant impact on survival. Interferon-alpha is a cytokine that has been studied in patients with gliomas and has demonstrated some activity in prior clinical trials.

Objectives:

* To compare the 2-year survival of pediatric patients with diffuse pontine gliomas receiving weekly subcutaneous low-dose pegylated interferon alfa-2b (PEG-Intron\[TM\]) injections after standard radiation therapy versus historical controls who have received radiation therapy alone.

* To define the toxicities of weekly low-dose pegylated interferon alfa-2b (PEG-Intron(Trademark)) in pediatric patients.

Eligibility:

Age: Patients must be less than or equal to 21 years of age.

Histological Diagnosis: Histologic confirmation is not required for this study. Patients must have a diffuse pontine glioma as diagnosed by MRI criteria below.

Radiologic Appearance: Patients must have a diffuse intrinsic tumor with the epicenter presumed to be in the pons. The T-2 weighted sequence must reveal a diffuse signal abnormality involving at least 50 percent of the pons.

Prior Therapy: The patient must have received adequate radiation therapy. Radiation must be completed between 2-10 weeks prior to the start of treatment with Peg-Intron\[TM\].

Design:

In this study, we plan to administer pegylated interferon alfa-2b (PEG-Intron\[TM\]) subcutaneously once a week to pediatric patients with diffuse pontine gliomas who have completed radiation therapy. The endpoint of the trial will be 2-year survival compared to historical controls.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Interferon Alfa	adjuvant therapy	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.
Interferon Alfa	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.

Primary Outcome Measures

Name	Time	Method
Two Year Survival of Pediatric Patients With Diffuse Pontine Gliomas	8 yrs 6 mo 0 days	Survival is measured from the date the patient is registered onto the protocol until the day of death and the date of diagnosis to the date of patient death.

Secondary Outcome Measures

Name	Time	Method
Median Time to Progression	8 yrs 11 mo 22 days	Time between the final day of treatment to the day of disease progression.
Number of Participants With Adverse Events	8 yrs 11 mo 22 days	Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Mean Quality of Life (QOL) Score at Baseline and Follow-Up	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.	QOL questionnaires will be performed prior to every cycle for patients age 6-18 years and their parents until cycle 27 and then prior to every third cycle until cycle 52 when the evaluations will become annual. The QOL (NIH Impact of Pediatric Illness Scale) is too detailed to be described and/or shown here. It is a questionnaire made up of approximately 40 questions-the answers are ranked from 1 to 5 with 5 being no impact and 1 being significant impact-For further details see the protocol.
Number of Participants With a Metabolic and Biological Change in the Brainstem Through Magnetic Resonance Imaging (MRI) Techniques	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.	MRI of the brain will be performed at the NCI prior to cycles 1, 2, 3, 5, 7, and continuing every other month until cycle 27. Following cycle 27 the patient will have an MRI performed every third cycle until cycle 52 at which time they will have an MRI performed annually, and when clinically indicated. Baseline MR images are compared with MR images performed during the various cycles (e.g. cycles 1, 2, 3...) Imaging was exploratory and the degree of change that is considered clinically significant rather than technique related is still being explored.