Ignite Creation Date:
2024-05-06 @ 1:35 PM
Last Modification Date:
2024-10-26 @ 1:16 PM
Study NCT ID:
NCT04065776
Status:
RECRUITING
Last Update Posted:
2023-12-12
First Post:
2019-08-20
Brief Title:
Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Low-grade gliomas LGGs are the most common brain tumors in children and a subset of these tumors are treated definitively with focal radiation therapy RT These patients often survive for many years after receiving RT and experience late deficits in memory Verbal recall is an important measure of memory and is associated with other important functional outcomes such as problem-solving independence of every-day functioning and quality of life Decline in memory as measured by verbal recall is associated with RT dose to the hippocampi Therefore this phase II study investigates the feasibility of reducing RT doses to the hippocampi ie hippocampal avoidance HA by using proton therapy for midline or suprasellar LGGs
Primary Objective
To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs Feasibility will be established if 70 of plans meet the first or second dose constraints shown below
1 First priority RT dose constraints for bilateral hippocampi volume receiving 40 CGE V40CGE 25 dose to 100 of Hippocampus D100 5CGE
2 Second priority RT dose constraints for bilateral hippocampi V40CGE 35 D100 10 CGE
Secondary Objectives
To estimate the 3-year event-free-survival EFS for LGGs treated with HA
To estimate the change in California Verbal Learning Test short-term delay CVLT-SD from baseline to 3 years and from baseline to 5 years
To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that 1 meet first priority RT dose constraints 2 meet second priority RT dose constraints but not first priority RT dose constraints and 3 that did not meet either first or second RT priority dose constraints
Exploratory Objectives
To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery including gold standard measures shown in the published studies to be sensitive to attention memory processing speed and executive function that will afford comparison to historical controls
To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi
To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography MET-PET uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology
To investigate the effect of BRAF alteration tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner
To investigate whether the methylation profiles of LGGs differ by tumor location thalamicmidbrain vs hypothalamicoptic pathway vs others and histologies pilocytic astrocytoma vs diffuse astrocytoma vs others which in conjunction with specific genetic alterations may stratify patients into different subgroups and highlight different therapeutic targets
To record longitudinal measures of circulating tumor DNA ctDNA in plasma and correlate these measures with radiographic evidence of disease progression
To bank formalin-fixed paraffin-embedded FFPEfrozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol
To quantify and characterize tumor infiltrating lymphocytes TILs and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment
To estimate the cumulative incidence of endocrine deficiencies vision loss hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy
Primary Objective
To determine the feasibility of HA with proton therapy in suprasellar or midline LGGs Feasibility will be established if 70 of plans meet the first or second dose constraints shown below
1 First priority RT dose constraints for bilateral hippocampi volume receiving 40 CGE V40CGE 25 dose to 100 of Hippocampus D100 5CGE
2 Second priority RT dose constraints for bilateral hippocampi V40CGE 35 D100 10 CGE
Secondary Objectives
To estimate the 3-year event-free-survival EFS for LGGs treated with HA
To estimate the change in California Verbal Learning Test short-term delay CVLT-SD from baseline to 3 years and from baseline to 5 years
To compare CVLT-SD and Cogstate neurocognitive scores in patients with proton therapy plans that 1 meet first priority RT dose constraints 2 meet second priority RT dose constraints but not first priority RT dose constraints and 3 that did not meet either first or second RT priority dose constraints
Exploratory Objectives
To describe the change in overall cognitive performance from baseline to 3 years and from baseline to 5 years with an age appropriate battery including gold standard measures shown in the published studies to be sensitive to attention memory processing speed and executive function that will afford comparison to historical controls
To characterize longitudinal changes in connection strength within brain networks in the first 3 years after proton therapy and to investigate associations between these changes and neurocognitive performance with focus on the hippocampi
To correlate the distribution and change in L-methyl-11C-methionine positron emission tomography MET-PET uptake to tumor progression and from baseline to 3 years and to investigate whether cases of pseudoprogression exhibit a differential pattern of uptake and distribution compared to cases of true progression after controlling for histology
To investigate the effect of BRAF alteration tumor histology and tumor location on PFS and OS in a prospective cohort of patients treated in a homogenous manner
To investigate whether the methylation profiles of LGGs differ by tumor location thalamicmidbrain vs hypothalamicoptic pathway vs others and histologies pilocytic astrocytoma vs diffuse astrocytoma vs others which in conjunction with specific genetic alterations may stratify patients into different subgroups and highlight different therapeutic targets
To record longitudinal measures of circulating tumor DNA ctDNA in plasma and correlate these measures with radiographic evidence of disease progression
To bank formalin-fixed paraffin-embedded FFPEfrozen tumors and whole blood from subjects for subsequent biology studies not currently defined in this protocol
To quantify and characterize tumor infiltrating lymphocytes TILs and to characterize the epigenetics of T cells and the T cell receptor repertoire within the tumor microenvironment
To estimate the cumulative incidence of endocrine deficiencies vision loss hearing loss and vasculopathy after proton therapy and compare these data to those after photon therapy
Detailed Description:
All patients will receive HA proton therapy to 522 CGE or 54 CGE in 29 or 30 fractions depending on tumor location Patients will receive weekly magnetic resonance imaging MRI scans during the course of proton therapy to monitor changes in solid tumor or cystic volume Such changes may prompt adaptive therapy to improve coverage or minimize the RT dose to healthy structures Neurocognitive outcomes sensitive to measures of memory and learning will be collected at baseline and continue to 5 years post therapy Disease evaluation will be monitored with brain MRI
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None