Pharmacodynamic Analyses of Metabolic Agents Following Brain Radiation

NCT05720624 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: MC220708NCI-2022-1063222-003783
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Central Nervous System Neoplasm

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 3 months

Secondary Outcomes (1)

• Incidence of treatment emergent adverse events (AEs) related to oxaloacetate following brain radiation (Arms B and Future Arms)

  Up to 3 months

Study Arms (4)

Cohort I, Arm A (standard of care therapy)

ACTIVE COMPARATOR

Patients in Cohort I, Arm A receive standard of care therapy. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study.

Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Questionnaire Administration

Cohort I, Arm B ( standard of care therapy, AEO)

EXPERIMENTAL

Patients in Cohort I, Arm B receive standard of care therapy and receive AEO PO BID for 1 month on study. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study.

Drug: Anhydrous Enol-oxaloacetate; Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Questionnaire Administration

Cohort II, Arm A (standard of care therapy)

ACTIVE COMPARATOR

Patients in Cohort II, Arm A receive standard of care therapy. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study.

Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Questionnaire Administration

Cohort II, Arm B (standard of care therapy, AEO)

EXPERIMENTAL

Patients in Cohort II, Arm B receive standard of care therapy and receive AEO PO BID for 3 months on study. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study.

Drug: Anhydrous Enol-oxaloacetate; Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Questionnaire Administration

Interventions

Anhydrous Enol-oxaloacetate DRUG

Given PO

Also known as: AEO, OXALOACETIC ACID

Cohort I, Arm B ( standard of care therapy, AEO); Cohort II, Arm B (standard of care therapy, AEO)

Best Practice OTHER

Receive standard of care therapy

Also known as: standard of care, standard therapy

Cohort I, Arm A (standard of care therapy); Cohort I, Arm B ( standard of care therapy, AEO); Cohort II, Arm A (standard of care therapy); Cohort II, Arm B (standard of care therapy, AEO)

Biospecimen Collection PROCEDURE

Undergo collection of CSF and blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort I, Arm A (standard of care therapy); Cohort I, Arm B ( standard of care therapy, AEO); Cohort II, Arm A (standard of care therapy); Cohort II, Arm B (standard of care therapy, AEO)

Magnetic Resonance Spectroscopic Imaging PROCEDURE

Undergo MRS imaging

Also known as: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging, 1H-nuclear magnetic resonance spectroscopic imaging, Magnetic Resonance Spectroscopy, MRS, MRS Imaging, MRSI, MS, Proton Magnetic Resonance Spectroscopic Imaging

Cohort I, Arm A (standard of care therapy); Cohort I, Arm B ( standard of care therapy, AEO); Cohort II, Arm A (standard of care therapy); Cohort II, Arm B (standard of care therapy, AEO)

Questionnaire Administration OTHER

Ancillary studies

Cohort I, Arm A (standard of care therapy); Cohort I, Arm B ( standard of care therapy, AEO); Cohort II, Arm A (standard of care therapy); Cohort II, Arm B (standard of care therapy, AEO)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years.
• Radiographic evidence or histopathologic confirmation of central nervous system (CNS) malignancy, with or without prior resection.
• Planned (cohort 1) or completed (cohort 2) fractionated brain radiation. The therapeutic brain radiation treatment volume should exceed 30 cubic cm, including the volume of brain tissue occupied by infiltrative disease. Volume occupied by solid non-infiltrative disease (e.g. meningioma, metastatic disease, cystic cavity, resection cavity), should be excluded from the estimated treatment volume.
• Provide written informed consent for the current study and the Neuro-oncology biorepository for archiving of CSF and blood samples collected on this protocol.
• Expected survival \>6 months and Karnofsky performance status \>= 60.
• Willing and able to adhere with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations.
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) \<3 x upper limit of normal (ULN) (=\< 5 x ULN for patients with baseline liver disease).
• Serum creatinine =\< 1.5 mg/dL.
• Ability to complete questionnaire(s) by themselves or with assistance.
• Willingness to provide mandatory CSF and blood and able to undergo magnetic resonance spectroscopy (MRS)/magnetic resonance imaging (MRI) with gadolinium.
• Male and female patients of childbearing potential must agree to use a dual method of contraception (a highly effective method of contraception in conjunction with barrier contraception) consistently and correctly from the first dose of study drug (Arm B only) until 90 days after the last dose of study drug.

You may not qualify if:

• Uncontrolled and/or intercurrent illness which limits safety of or compliance to study proceedings.
• Vulnerable populations: pregnant or nursing women (Arm B exempt), prisoners, mentally handicapped.
• Patients with recurrent brain tumor after prior radiation.
• Cohort 1 only: History of prior brain radiation, with prior cumulative target radiation treatment volume exceeding 2 cubic centimeters.
• Patients who do not have an implanted CSF access device (who would thus require multiple lumbar punctures \[LPs\] for participation) should be excluded if they have any contra-indication to lumbar puncture. This includes but is not limited to obstructive hydrocephalus or posterior fossa mass or cerebral edema that could increase the risk of brain herniation.
• Patients who do not have an implanted CSF device and are on anti-platelet therapy (other than Aspirin which is considered low risk) or anticoagulation (coumadin, Eliquis) must discontinue these prior to each lumbar puncture to participate. Patients unwilling or unable to safely do so should not be enrolled.
• Participants who are unable to swallow tablets or who are at risk for impaired absorption of oral medication. NOTE: This includes but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection.
• Patients with recent (\<3 months \[mo\]) administration of, or known hypersensitivity or allergy to any active study drug currently available for randomization (initially oxaloacetate).
• Current use of resveratrol, CoQ10 (coenzyme Q10), coconut oil/other medium chain triglyceride-containing (i.e. Axona) supplements, or curcumin will be excluded unless willing to discontinue them 14 days prior to the start of baseline visits and remain off for study duration.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Central Nervous System Neoplasms

Interventions

Oxaloacetic Acid; Practice Guidelines as Topic; Standard of Care; Specimen Handling; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Oxaloacetates; Oxalates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Keto Acids; Guidelines as Topic; Quality Assurance, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality Indicators, Health Care; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Terence C. Burns, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 9, 2023
• Study Start: October 20, 2025
• Primary Completion: October 20, 2025
• Study Completion: October 20, 2025
• Last Updated: October 22, 2025

Record last verified: 2025-10

Locations

US (1)