Proton Beam Radiation Therapy in Treating Young Patients Who Have Undergone Biopsy or Surgery for Medulloblastoma or Pineoblastoma

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers radiation directly to the area where a tumor was surgically removed may kill any remaining tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well proton beam radiation therapy works in treating young patients who have undergone biopsy or surgery for medulloblastoma or pineoblastoma.

Detailed Description
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OBJECTIVES: Determine the 3-year incidence and severity of ototoxicity in young patients with medulloblastoma or pineoblastoma treated with adjuvant proton beam craniospinal and posterior fossa radiotherapy. Determine the incidence of primary hypothyroidism and other endocrine dysfunction (neuroendocrine and end organ) in patients treated with this regimen. Determine the incidence and severity of neurocognitive abnormalities in patients treated with this regimen. Determine the acute side effects of this regimen, including esophagitis, upper and lower gastrointestinal tract disease, and weight loss, in these patients. Determine the 3-year progression-free survival rate of patients treated with this regimen. OUTLINE: Patients are stratified according to risk (standard vs high). Patients receive proton beam craniospinal and posterior fossa radiotherapy once daily 5 days a week for 6-8 weeks*. NOTE: *Unless otherwise specified by a co-existing protocol. Patients undergo neurocognitive evaluation at baseline or within 3 months after completion of radiotherapy and then at 1, 3, and 5 years. Patients also undergo endocrine evaluation at baseline and then annually for 5 years; and audiology evaluation at baseline, before each course of cisplatin-based chemotherapy (if receiving this), and then annually for 5 years. After completion of study treatment, patients are followed every 3-6 months for 2-5 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Official Title
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Phase II Study of Craniospinal and Posterior Fossa Irradiation Using Proton Beam Radiotherapy for Medulloblastoma and Pineoblastoma: Assessment of Acute and Long Term Sequelae

Conditions
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Brain and Central Nervous System Tumors, Long-term Effects Secondary to Cancer Therapy in Children

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 medulloblastoma or pineoblastoma Standard-risk or high-risk disease Must have undergone biopsy or attempted surgical resection of the tumor within the past 35 days Requires craniospinal irradiation PATIENT CHARACTERISTICS: Age 3 to 21 Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No more than 1 prior chemotherapy regimen No prior IV or intrathecal methotrexate No prior intrathecal thiotepa Concurrent cisplatin-based chemotherapy, including chemotherapy administered on another study, allowed Endocrine therapy Not specified Radiotherapy No prior radiotherapy Surgery See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 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: Radiation therapy<br>This is a single arm study of radiation therapy with protons to standard doses. | Radiation: radiation therapy<br>* Radiation therapy with proton beam to standard doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Ototoxicity | Percentage participants who experienced ototoxicity as measured by Common Toxicity Criteria for Adverse Events (CTCAE) v3.0 after the completion of radiation therapy in the overall participant population and by baseline measure subgroups. Incidence is shown after follow-up of 3 years, 5 years, 7 years, and 10 years. | 3 Years, 5 years, 7 years, 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 3 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 3 years of follow-up (as determined by CTCAE 3.0). Incidence is grouped by hormone type and risk group | 3 years | 
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 5 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 5 years of follow-up (as determined by CTCAE 3.0). Incidence is shown by hormone type and risk group. | 5 years | 
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | Percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) after 7 years of follow-up, as determined by CTCAE 3.0. Incidence is shown by hormone type and risk group | 7 years | 
| Cumulative Incidence of Endocrine Dysfunction (Neuroendocrine and End Organ Defects) at 7 Years | percentage of participants who experienced endocrine dysfunction (neuroendocrine and end organ defects) as determined by CTCAE 3.0) at year 3, year 5, and year 7 of follow-up. | 3 years, 5 years, 7 years | 
| Mean Change Per-Year in Neurocognitive Outcomes | The mean change per-year in neurocognitive outcomes as assessed by Wechsler Intelligence Scale for Children version 4 (WISC-IV). The test measures the Full Scale Intelligence Quotient (FSIQ) of children with the use of four indices; the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), working memory test, and a processing speed test. FSIQ and the four indices are all assessed on a bell curve scale that has an average score of 100 and standard deviation of 15 points in the general population, meaning on average 68% of test takers would be within +/- 15 points of 100 and 95% within +/- 30 points. Higher scores represent higher intelligence and lower score represent reduced intelligence. Participants were assessed for changes in score with the use of repeated testing during a median follow-up time of 5.2 years. Repeated measures were taken at baseline, 1, 3, 5, and 7 years or until the participant was not available for evaluation (whichever comes first). | Baseline, 1, 3, 5, 7 years | 
| Progression Free Survival | The percentage of participants with progression free survival after five, seven, and ten years in the overall population and by risk and histological group. | 5 years, 7 years, 10 years | 
| Overall Survival | the percentage of participants surviving after five and seven years and at the end of follow-up in the overall population. Survival is shown by risk and histological group. | 5 years, 7 years, 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long-term effects secondary to cancer therapy in children, untreated childhood medulloblastoma, untreated childhood pineoblastoma