LET Optimized IMPT in Treating Pediatric Patients With Ependymoma

Phase 1

Recruiting

Interventions: Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
Other: Quality-of-Life Assessment
Other: Questionnaire Administration

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Treatment (LET optimized IMPT)	Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy	Patients receive LET optimized IMPT for up to 6 weeks.
Treatment (LET optimized IMPT)	Questionnaire Administration	Patients receive LET optimized IMPT for up to 6 weeks.
Treatment (LET optimized IMPT)	Quality-of-Life Assessment	Patients receive LET optimized IMPT for up to 6 weeks.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	Up to 6 months post treatment	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.

Secondary Outcome Measures

Name	Time	Method
Identify imaging biomarkers of structural and biological changes after proton therapy	Up to 24 months post-treatment	Descriptive statistics will be used to summarize the study data.
Quantitative image biomarkers	Up to 24 months post-treatment	Descriptive statistics will be used to summarize the study data.
Validity of relative biological effectiveness models	Up to 24 months post-treatment	Descriptive statistics will be used to summarize the study data.
Overall survival	Up to 24 months post treatment	The method of Kaplan and Meier will be used to provide estimates.
Incidence of late and acute toxicities	Up to 24 months post treatment	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.
Progression-free survival	Up to 24 months post treatment	The method of Kaplan and Meier will be used to provide estimates.
Disease outcomes following the use of a simultaneous integrated boost	Up to 24 months post-treatment	Descriptive statistics will be used to summarize the study data.

Locations (2): Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States