Radiation Therapy in Treating Young Patients With Gliomas

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well radiation therapy works in treating young patients with gliomas.

Detailed Description
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OBJECTIVES: Primary Determine the marginal-failure rate in young patients with low-grade gliomas treated with reduced-field conformal radiotherapy. Secondary Determine the progression-free survival, event-free survival, and overall survival rates of young patients treated with this regimen. Determine quality of life of patients treated with this regimen. Correlate MIB-1 labeling index with progression-free survival and overall survival of these patients. OUTLINE: This is a multicenter study. Patients undergo reduced-field conformal radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline or 6 weeks after completion of study treatment and then at 2 and 5 years (closed as of 10/27/2010). After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Official Title
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A Phase II Study of Conformal Radiotherapy In Patients With Low-Grade Gliomas

Conditions
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Brain Tumor, Central Nervous System Tumor

Intervention / Treatment
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* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* low-grade glioma, including any of the following: Juvenile pilocytic astrocytoma (JPA) or pleomorphic JPA Diffuse astrocytoma, including any of the following subtypes: Fibrillary astrocytoma Gemistocytic astrocytoma Subependymal giant cell astrocytoma Pleomorphic xanthoastrocytoma Low-grade oligoastrocytoma Low-grade oligodendroglioma Low-grade glioma not otherwise specified NOTE: *Patients with chiasmatic lesions who have contiguous extension of tumor into other regions of the visual pathway by CT scan or MRI are eligible without histopathologic confirmation; repeat biopsy required for patients with recurrent tumors that enhance but whose initial tumor did not Measurable disease by radiography Meets any of the following criteria: Progressive nonresectable disease Any location in the brain Patients with a less than gross total resection are eligible provided they are symptomatic from their tumor OR the risk from neurologic impairment with progression is high enough to warrant immediate treatment Has undergone biopsy only Must have received ≥ 1 course of prior chemotherapy (for patients < 10 years of age) Prior chemotherapy optional (for patients ≥ 10 years of age) No type-1 neurofibromatosis No evidence of leptomeningeal dissemination PATIENT CHARACTERISTICS: Age 3 to 20 Performance status ECOG 0-2 OR Karnofsky 50-100% (for patients > 16 years of age) OR Lansky 50-100% (for patients ≤ 16 years of age) Life expectancy At least 1 year Hematopoietic Absolute neutrophil count ≥ 1,000/mm^3 Platelet count ≥ 100,000/mm^3 (transfusion independent) Hemoglobin ≥ 10.0 g/dL (transfusions allowed) Hepatic Not specified Renal Not specified Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception Not in status epilepticus, coma, or requiring assisted ventilation prior to study entry Patients with a seizure disorder are eligible provided they are on anticonvulsants AND disease is well controlled PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Recovered from prior chemotherapy No concurrent chemotherapy Endocrine therapy Concurrent dexamethasone allowed provided patient has been on a stable dose for ≥ 2 weeks prior to study entry Concurrent dexamethasone allowed for symptoms of increased intracranial pressure Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (radiotherapy)<br>Patients undergo reduced-field conformal radiation therapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity. | Radiation: radiation therapy<br>* Undergo 3D-CRT Undergo proton radiation therapy Undergo IMRT<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Marginal-failure Rate | Patients who do not recur as well as those with either central or distant recurrence would be treatment successes for this endpoint. Monitoring will be based on a Bayesian rule, with binomial likelihood and a Beta on the parameter p, the proportion of failures that are marginal failures. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Probability | To estimate the progression-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation. | 3 years | 
| Event-free Survival Probability | To estimate the event-free survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation | 3 years | 
| Overall Survival Probability | To estimate the overall survival rate for patients with recurrent, progressive or symptomatic low-grade gliomas after treatment with reduced field conformal radiation. | 3 years | 
| Quality of Life (QOL) | QOL accessed using the Behavior Assessment System for Children (BASC), the Adaptive Behavior Assessment System (ABAS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Symptom Checklist-90-R (SCL-90-R). | Up to 5 years | 
| MIB-1 Labeling Index Using Immunohistochemical Techniques With the MIB-1 Antibody According to Established Methods | The MIB-1 labeling Index will be calculated as the percentage of tumor nuclei that are immunoreactive. | At baseline | 
| Correlation MIB-1 Labeling Index With PFS | The primary methods of analysis will be via stratified Cox regression | Up to 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood oligodendroglioma, recurrent childhood cerebellar astrocytoma, recurrent childhood cerebral astrocytoma, childhood low-grade cerebral astrocytoma, recurrent childhood visual pathway and hypothalamic glioma, untreated childhood cerebellar astrocytoma, untreated childhood visual pathway and hypothalamic glioma