LET Optimized IMPT in Treating Pediatric Patients With Ependymoma

Pilot Trial of LET Optimized IMPT for Pediatric Patients With Ependymoma

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.

Study Overview

• Status: Recruiting
• Conditions: Ependymoma; Anaplastic Ependymoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David Grosshans; Phone Number: 713-563-2300; Email: dgrossha@mdanderson.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Not yet recruiting
      • Massachusetts General Hospital Cancer Center
      • Principal Investigator: Shannon M. MacDonald
      • Contact: Tristin Flood; Email: TEFLOOD@mgh.harvard.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: David R. Grosshans; Phone Number: 713-563-2300
      • Principal Investigator: David R. Grosshans

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 22 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (LET optimized IMPT); Patients receive LET optimized IMPT for up to 6 weeks.

Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy; Given LET optimized IMPT; Other Names: LET-Optimized IMPT; LET-Optimized Intensity Modulated Proton Therapy; Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David R Grosshans, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ependymoma
• Other Study ID Numbers: 2018-0344 (Other Identifier: M D Anderson Cancer Center); P30CA016672 (U.S. NIH Grant/Contract); NCI-2018-02519 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U19CA021239 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No