Cognitive Changes of IDH-mutant and IDH-wildtype Glioma Patients After Chemoradiotherapy With Radiation Dose to the Resting State Networks

Study Purpose

Neurocognitive decline after radiation therapy is one of the most concerning complication for brain tumor patients and neuro-oncologists. There are increasing technological advances in evaluating the brain's neural connections responsible for the neurocognitive processes. For example, resting-state functional MRI (RS-fMRI) is an advanced imaging method that can identify the spatiotemporal distribution of the intrinsic functional networks within the brain (also referred to as resting state networks (RSNs) without requiring specific tasks by the imaged participants. Although there is evidence that shows that avoidance of specific neural networks during radiation therapy planning can lead to improved preservation of neurocognitive function afterward, it is important to first identify the most vulnerable and clinically relevant RSNs that correspond to cognitive decline. In this study, the investigators will prospectively perform RS-fMRI and neurocognitive evaluation using the NIH Toolbox Cognitive Battery (NIHTB-CB) on patients with gliomas before and after radiation therapy to generate preliminary data on what RSNs are most vulnerable to radiation injury leading to cognitive decline. A benign brain tumor cohort will also be followed to serve as control. The investigators will also evaluate the feasibility of incorporating RS-fMRI with radiation planning software for treatment optimization.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Cohort A: histological diagnosis of IDH-mutant astrocytoma or oligodendroglioma, WHO grade II-IV.
IDH-mutation may be either by immunohistochemistry (IHC) or next-generation sequencing (NGS) as per routine clinical care.
  • - Cohort B: histological diagnosis of IDH-wildtype astrocytoma, WHO grade II-IV.
IDH-wildtype status or absence of IDH-mutation may be either by IHC or NGS as per routine clinical care. The IDH-wildtype patients should have >80% probability to be alive in 6 months, and the online nomogram calculator below may be used to estimate the 6-month probability: http://cancer4.case.edu/rCalculator/rCalculator.html (Gittleman et al., 2016). The ideal patients are favorable IDH-wildtype astrocytoma patients who are expected to have prolonged survival, such as age ≤ 40 or grade 2-3 tumors.
  • - Cohort C: any non-infiltrative benign brain tumor histology, including but not limited to meningioma, pituitary tumor, schwannoma, craniopharngioma, hemangioblastoma, hemangiopericytoma, pineal tumor, pilocytic astrocytoma, and ganglioglioma.
  • - At least 18 years of age.
  • - Karnofsky performance status (KPS) of at least 70% - Eligible for and planning to receive standard fractionated RT, which can be either photon-based or proton beam therapy.
  • - May be part of other clinical trials and can receive chemotherapy or experimental agents concurrently with or after RT as long as the other clinical trial does not exclude participation in this non-therapeutic study.
  • - Females of childbearing potential (defined as a female who is non-menopausal or surgically sterilized) must be willing to use an acceptable method of birth control (i.e., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • - Able to understand and willing to sign an IRB-approved written informed consent document (legally authorized representative permitted).

Exclusion Criteria:

  • - Prior cranial RT or RT to the head and neck where potential field overlap may exist.
  • - Gliomatosis, leptomeningeal, or metastatic involvement.
  • - Medical contraindication to MRI (e.g., unsafe foreign metallic implants, incompatible pacemaker, inability to lie still for long periods, severe to end-stage kidney disease or on hemodialysis).
  • - Require anesthesia to undergo MRI (e.g. severe claustrophobia), which would interfere with RS-fMRI acquisition and processing.
  • - Pregnant or breastfeeding.
  • - Non-English speaking, as the cognitive assessments will only be available in English.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04975139
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Washington University School of Medicine
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Jiayi Huang, M.D.
Principal Investigator Affiliation Washington University School of Medicine
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioma
Study Website: View Trial Website
Arms & Interventions

Arms

: IDH-mutant astrocytoma or oligodendroglioma

After enrollment and before beginning standard of care radiation therapy (RT), MRI will be obtained for RT planning as per standard of care (SOC), and the RS-fMRI sequences will be performed at the same time. At approximately 6 months, 2 years, 5 years, and 10 years from the completion of RT, RS-fMRIs will be performed.

: IDH-wildtype astrocytoma

After enrollment and before beginning standard of care radiation therapy (RT), MRI will be obtained for RT planning as per standard of care (SOC), and the RS-fMRI sequences will be performed at the same time. At approximately 6 months, 2 years, 5 years, and 10 years from the completion of RT, RS-fMRIs will be performed.

: Benign Brain Tumor

After enrollment and before beginning standard of care radiation therapy (RT), MRI will be obtained for RT planning as per standard of care (SOC), and the RS-fMRI sequences will be performed at the same time. At approximately 6 months, 2 years, 5 years, and 10 years from the completion of RT, RS-fMRIs will be performed.

Interventions

Device: - RS-fMRI

Advanced imaging method that can identify the spatiotemporal distribution of the intrinsic functional networks within the brain

Contact a Trial Team

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Washington University School of Medicine, Saint Louis, Missouri

Status

Recruiting

Address

Washington University School of Medicine

Saint Louis, Missouri, 63110

Site Contact

Jiayi Huang, M.D.

[email protected]

314-362-8567

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