This phase I trial studies the impact of taking drugs (agents) that target altered brain metabolism following standard of care brain radiotherapy. Radiotherapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. However, radiotherapy can also cause harmful effects to normal brain functioning. One drug, called anhydrous enol-oxaloacetate (AEO), has previously been studied in ischemic stroke, Alzheimer's disease, Parkinson's disease, and glioma. Drugs such as AEO may help preserve or restore healthy brain function after brain radiotherapy compared to the standard practice which consists of no drugs.
PRIMARY OBJECTIVE: I. Determine the feasibility of serial cerebrospinal fluid (CSF) assessments to evaluate the pharmacodynamic impact of agents targeting radiation-induced biology administered following completion of brain radiation. SECONDARY OBJECTIVE: I. Assess the safety of study drug(s) as quantified by dose-limiting toxicities. CORRELATIVE RESEARCH OBJECTIVES: I. Investigate the relationship of the global CSF metabolome with magnetic resonance spectroscopy metabolite profile. II. Investigate the relationship between brain radiation dose/volume and metabolic alterations in CSF. III. Investigate the impact of metabolic therapy on early cognitive effects of radiotherapy in patients with brain tumors. IV. Utilize paired blood samples to investigate association between the CSF and systemic metabolome. V. Utilize paired stool samples to investigate association between the blood and CSF metabolome with the gastrointestinal microbiome. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I (EARLY POST-RADIATION): Patients within Cohort I are assigned to 1 of 2 arms. ARM A: Patients receive standard of care therapy. ARM B: Patients receive standard of care therapy and receive AEO orally (PO) two times daily (BID) for 1 month on study. COHORT II (DELAYED POST-RADIATION): Patients within Cohort II are assigned to 1 of 2 arms. ARM A: Patients receive standard of care therapy. ARM B: Patients receive standard of care therapy and receive AEO PO BID for 3 months on study. Patients in all cohorts and arms also undergo magnetic resonance spectroscopy (MRS) imaging, collection of cerebrospinal fluid (CSF), and collection of blood on study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Given PO
Receive standard of care therapy
Undergo collection of CSF and blood
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Determine the feasibility of completing serial cerebrospinal fluid (CSF) collections for pharmacodynamic analyses.
Successful collection of at least 1cc of CSF at each of 3 timepoints with successful quantification of glutamate and lactate from each sample.
Time frame: Up to 3 months
Incidence of treatment emergent adverse events (AEs) related to oxaloacetate following brain radiation (Arms B and Future Arms)
To assess the safety and tolerability of the study drug(s). Safety will be assessed in that the study drug will not have a Common Terminology Criteria for Adverse Events (CTCAE) (version \[v\] 5.0) grade \>3 in \>20% of participants. Tolerability will be assessed in that \>60% of participants are able to complete the initial 28-day study treatment period without AE precluding continuation of study drug (even if not CTCAE \>3).
Time frame: Up to 3 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Undergo MRS imaging
Ancillary studies