Observational Trial of the Impact of Radiation Dose in Children With Brain and Skull Base Tumors.

Prospective Observational Trial of the Impact of Radiation Dose on Brain Morphology, Volumetric Changes, Endocrine Function, and Neurocognitive Function Following Cranial Radiation Therapy in Children With Brain and Skull Base Tumors.

This is a prospective, observational clinical trial investigating the morphological and volumetric changes in the brain following cranial Radiation Therapy in pediatric patients with brain or skull base tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Cancer; Brain Tumor; Skull Base Tumor

Detailed Description

Brain injury is a known complication of cranial RT, but little is known about the factors that predispose patients to such injury. The brain is a highly interconnected organ linked through neuronal connections, cellular migration, and vascular supply and is endowed with exquisitely radiosensitive stem cell niches responsible for neuro-regeneration. To date, the effects of brain radiation have been quantified in few brain substructures. The majority of publications on this topic have focused on regions receiving higher doses. Even low dose radiation exposure, however has global implications on brain development and function, and its effects are less well studied. It is increasingly recognized that radiation damage to one brain region can potentially affect brain development more broadly. This has important implications on RT planning and the potential for understanding its long-term effects.

In this protocol, the investigators aim to measure serum inflammatory cytokine levels and other molecular biomarkers at baseline and post-exposure in an exploratory manner to investigate potential associations with the risk of developing volumetric changes in the brain and radiation-induced toxicities.

This study will observe sixty (60) patients under the age of 21 with brain or base of skull tumor. The study team will observe the effect of radiation therapy per the study protocol versus standard of care.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

• Study Contact: Name: Matthew D Hall, MD; Phone Number: (786) 527-8140; Email: MatthewHa@BaptistHealth.net

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health South Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study sample size will be 60 patients. This sample size was selected to ensure an adequate distribution of primary tumor diagnoses and dosimetric variation in major brain substructures treated based on tumor location/brain regions treated. The estimated case distribution based on historical data from 2007-2015 will be: Craniopharyngioma 20%, Ependymoma 20%, Low Grade Glioma 20%, Medulloblastoma/PNET 15%, Sarcoma 10%, Other 15%.

Description

Inclusion Criteria:

• Patient (parent) must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment. Written assent will be obtained as per Institutional guidelines.
• Patients (Age equal to or less than 35 years old) that are planned to receive photon or proton RT to the brain according to standard of care are eligible to participate.
• Patients that are planned to receive fractionated RT at 1.2-2.0 Gy RBE dose per fraction per standard of care are eligible to participate. If patients are planned to receive an alternative dose/fractionation regimen, then they should be treated according to standard of care and should not be enrolled.
• Zubrod/Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

Exclusion Criteria:

• Patient cannot undergo MRI without contrast as per standard of care
• Patient and family do not speak English or Spanish
• Patient receiving treatment with non-curative intent
• Patients with an expected 3-year overall survival less than 50%

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure temporal changes in brain volumes	Measure temporal changes in brain volumes after exposure to therapeutic RT and to correlate these changes with absorbed dose.	Baseline, 6 Months, 12 months, 18 months, 24 months and 3-5 years
Measure temporal changes in morphometry	Measure temporal changes in morphometry after exposure to therapeutic RT and to correlate these changes with absorbed dose.	Baseline, 6 Months, 12 months, 18 months, 24 months and 3-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphometric changes in the brain	The secondary aims for this study are to correlate morphometric changes in the brain with the development of late treatment-related effects, including measurable neurocognitive, endocrine, and quality of life effects.	Baseline, 6 Months, 12 months, 18 months, 24 months and 3-5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure molecular biomarkers	Serum pro-inflammatory and anti-inflammatory cytokine levels will be measured at baseline and during follow-up as part of an exploratory hypothesis-generating correlate study to analyze potential associations with risk of radiation-induced toxicities and volumetric changes in the brain.	Baseline, 6 Months, 12 months, 18 months, 24 months and 3-5 years

Collaborators and Investigators

• Sponsor: Baptist Health South Florida
• Collaborators: Nicklaus Children's Hospital f/k/a Miami Children's Hospital
• Investigators: Principal Investigator: Matthew D Hall, MD, Miami Cancer Institute (MCI) at Baptist Health South Florida

Publications and helpful links

Helpful Links

• Miami Cancer Institute website

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2019
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: pediatrics; brain; pediatrics brain cancer; skull
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Musculoskeletal Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Bone Diseases; Skull Neoplasms; Bone Neoplasms; Neoplasms; Brain Neoplasms; Skull Base Neoplasms
• Other Study ID Numbers: 2018-LLB-HALL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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