Evaluation of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma (NCT04065776)
A Phase II Study of Hippocampal-Avoidance Using Proton Therapy in Low-Grade Glioma
🩺 Plain-English Summary (8th-Grade Level)
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 (i.e., 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 (thalamic/midbrain vs. hypothalamic/optic 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 (FFPE)/frozen 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.
Who can join: To join this study, participants generally need to meet the listed inclusion criteria (13 items) and avoid the listed exclusions (9 items).
Location: Mayo Clinic — Rochester, Minnesota
Age range: 6 Years to 21 Years
🧪 Interventions in This Study
- Hippocampal-avoidance proton therapy (RADIATION)
📋 "Do I Qualify?" — 1-Minute Self Screener
Instant ChecklistCheck every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).
Usually NOT eligible if any of the following apply:
- Exclusion Criteria:
- Patients may not have received prior CNS radiation.
- Patients with gross total resection and no measurable disease via MRI are not eligible. Patients must have measurable disease of at least 1 cm via MRI.
- Patients with evidence of metastatic disease are not eligible.
- Patients with WHO grade II midline tumors that harbor the H3K27M mutation, IDH-mutant gliomas, grade II ependymomas and subependymomas, pituicytomas, spindle cell oncocytomas, or granular cell tumors of the sellar region are not eligible.
- Patients with tumors that directly invade the hippocampus or with gross tumor volumes that extend into the hippocampus are not eligible.
- Patients with tumors in the spine or cervicomedullary junction.
- Females of child-bearing potential cannot be pregnant or breast feeding. Female participants \> 10 years of age or post menarche must have a negative serum or urine pregnancy test before enrollment. Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
- Patients who are status post resection of bilateral hippocampi. Patients who are status post resection of one hippocampus will be eligible for the study and the hippocampal dose constraints will be applied to the intact hippocampus.
🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.
📍 All Participating Trial Locations (2 Sites)
- Mayo Clinic — Rochester, Minnesota
- St. Jude Children's Research Hospital — Memphis, Tennessee
📞 Contact the Study Coordinator
Phone: (888) 226-4343
Email: referralinfo@stjude.org
Coordinator details come directly from the registered NIH protocol. Confirm the study is still recruiting before traveling.
💰 Cost, Insurance & Patient Rights
- 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
- Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
- Voluntary Participation: You may withdraw at any time without affecting your standard medical care.
- 💵 Compensation indicated: All patients will receive HA proton therapy to 52.2 CGE or 54 CGE in 29 or 30 fractions, depending on tumor location.
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💡 How to Participate
- Check the checklist above to see if you may qualify.
- Contact the study coordinator using the phone/email above.
- Ask about the visit schedule, what is covered at no cost, and any travel support.
- Confirm with your own doctor before making a decision.