LET Optimized IMPT in Treating Pediatric Patients With Ependymoma

Study Overview
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Brief Summary
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This phase I trial studies the side effects of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) in treating pediatric patients with ependymoma. Radiation therapy such as LET optimized IMPT, uses proton beams to kill tumor cells and shrink tumors without damaging surrounding normal tissues.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the safety of linear energy transfer (LET) optimized image modulated proton therapy (IMPT) (bio-IMPT) for pediatric patients with ependymoma. SECONDARY OBJECTIVES: I. To utilize advanced multiparametric magnetic resonance (MR) imaging to identify imaging biomarkers of structural and biological changes after proton therapy in pediatric ependymoma patients. II. To compare quantitative image biomarkers in patients treated with bio-IMPT and standard proton therapy using a voxel level analysis. III. To test and evaluate the validity of relative biological effectiveness (RBE) models and enhance their precision based on prospectively collected clinical image biomarkers. IV. To evaluate acute and late toxicities, including pseudoprogression and symptom burden, in patients treated with bio-IMPT. V. To estimate progression-free survival (PFS) and overall survival (OS). VI. To evaluate disease outcomes following the use of a simultaneous integrated boost (SIB) for pediatric ependymoma patients with gross residual disease following surgery. OUTLINE: Patients receive LET optimized IMPT for up to 6 weeks. After completion of study treatment, patients are followed up at 1 month, then every 3 months for up to 24 months.

Official Title
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Pilot Trial of LET Optimized IMPT for Pediatric Patients With Ependymoma

Conditions
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Anaplastic Ependymoma, Ependymoma

Intervention / Treatment
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* Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previous pathologic confirmation of ependymoma, World Health Organization (WHO) grade II or III Disease must be confined to the brain (no evidence of spread on MR imaging of the spine or on staging lumbar puncture) Patient may not receive chemotherapy concurrent with radiation Signed informed consent by patient and/or parents or legal guardian Lansky performance status score of 50 -100 Exclusion Criteria: Patients with previous radiation therapy to the brain Ependymoma of the spine Disseminated ependymoma requiring craniospinal radiation therapy Pregnancy Inability to undergo MR imaging Inability to receive gadolinium-based contrast agent

Ages Eligible for Study
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Maximum Age: 22 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 (LET optimized IMPT)<br>Patients receive LET optimized IMPT for up to 6 weeks. | Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy<br>* Given LET optimized IMPT<br>* Other names: Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT);Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | The safety of linear energy transfer-optimized intensity modulated proton therapy will be defined by treatment failures which include imaging changes consistent with necrosis in the presence of Common Terminology Criteria for Adverse Events version 4.03 symptoms of grade 3 brain necrosis and/or local recurrence within the first 6 months from the end of proton therapy. | Up to 6 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify imaging biomarkers of structural and biological changes after proton therapy | Descriptive statistics will be used to summarize the study data. | Up to 24 months post-treatment | 
| Quantitative image biomarkers | Descriptive statistics will be used to summarize the study data. | Up to 24 months post-treatment | 
| Validity of relative biological effectiveness models | Descriptive statistics will be used to summarize the study data. | Up to 24 months post-treatment | 
| Incidence of late and acute toxicities | Descriptive statistics will be used to summarize the study data. For each study cohort, we will tabulate treatment- failures and other relevant clinically-related features. Interval estimates for proportions will be provided using exact 95% confidence intervals. | Up to 24 months post treatment | 
| Progression-free survival | The method of Kaplan and Meier will be used to provide estimates. | Up to 24 months post treatment | 
| Overall survival | The method of Kaplan and Meier will be used to provide estimates. | Up to 24 months post treatment | 
| Disease outcomes following the use of a simultaneous integrated boost | Descriptive statistics will be used to summarize the study data. | Up to 24 months post-treatment |