Malignant Central Nervous System NeoplasmPhase 1NCT05720624
Pharmacodynamic Analyses of Metabolic Agents Following Brain Radiation
A Phase 1 study testing Anhydrous Enol-oxaloacetate, Best Practice and Biospecimen Collection in people with Malignant Central Nervous System Neoplasm, run by Mayo Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Central Nervous System Neoplasm
- What is being tested?
- Anhydrous Enol-oxaloacetate, Best Practice and Biospecimen Collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Oct 2025to 20 Oct 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- Assess the safety of study drug(s) as quantified by dose-limiting toxicities.
CORRELATIVE RESEARCH OBJECTIVES:
- 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.
- 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.
- Being tested
- Anhydrous Enol-oxaloacetate, Best Practice, Biospecimen Collection, Magnetic Resonance Spectroscopic Imaging, Questionnaire Administration
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anhydrous Enol-oxaloacetateDrug
Also called AEO, OXALOACETIC ACID
Given PO
Best PracticeOther
Also called standard of care, standard therapy
Receive standard of care therapy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of CSF and blood
Magnetic Resonance Spectroscopic ImagingProcedure or surgery
Also called 1H- Nuclear Magnetic Resonance Spectroscopic Imaging, 1H-nuclear magnetic resonance spectroscopic imaging, Magnetic Resonance Spectroscopy, MRS
Undergo MRS imaging
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Anhydrous Enol-oxaloacetate; Other: Best Practice; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Spectroscopic Imaging; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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).
Measured: Up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2023
- Study start20 Oct 2025
- Primary completion20 Oct 2025
- Study completion20 Oct 2025
Why it stopped: Funding issues
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Central Nervous System NeoplasmStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Terence C. Burns, MD, PhD, Principal investigator, Mayo Clinic in Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05720624
- Sponsor's protocol ID
- MC220708
- Other IDs
- NCI-2022-10632, 22-003783, MC220708
- Status last verified
- Oct 2025
- First submitted
- 17 Jan 2023
- Last updated
- 22 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamic Analyses of Metabolic Agents Following Brain Radiation
- ClinicalTrials.gov ID
- NCT05720624
- Acronym / sponsor ID
- MC220708
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding issues
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 20 Oct 2025 (actual)
- Primary completion
- 20 Oct 2025 (actual)
- Study completion
- 20 Oct 2025 (actual)
- First posted
- 9 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- 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:
- Assess the safety of study drug(s) as quantified by dose-limiting toxicities.
CORRELATIVE RESEARCH OBJECTIVES:
- 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.
- 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 design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort I, Arm A (standard of care therapy) | Active comparator | Other: Best Practice, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Questionnaire AdministrationPatients in Cohort I, Arm A receive standard of care therapy. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study. |
| Cohort I, Arm B ( standard of care therapy, AEO) | Experimental | Drug: Anhydrous Enol-oxaloacetate, Other: Best Practice, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Questionnaire AdministrationPatients 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. |
| Cohort II, Arm A (standard of care therapy) | Active comparator | Other: Best Practice, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Questionnaire AdministrationPatients in Cohort II, Arm A receive standard of care therapy. Patients also undergo MRS imaging, collection of CSF, and collection of blood on study. |
| Cohort II, Arm B (standard of care therapy, AEO) | Experimental | Drug: Anhydrous Enol-oxaloacetate, Other: Best Practice, Procedure: Biospecimen Collection, Procedure: Magnetic Resonance Spectroscopic Imaging, Other: Questionnaire AdministrationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anhydrous Enol-oxaloacetateAlso: AEO, OXALOACETIC ACIDGiven PO | Drug | Cohort I, Arm B ( standard of care therapy, AEO), Cohort II, Arm B (standard of care therapy, AEO) |
| Best PracticeAlso: standard of care, standard therapyReceive standard of care therapy | Other | 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 CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo collection of CSF and blood | Procedure or surgery | 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 ImagingAlso: 1H- Nuclear Magnetic Resonance Spectroscopic Imaging, 1H-nuclear magnetic resonance spectroscopic imaging, Magnetic Resonance Spectroscopy, MRSUndergo MRS imaging | Procedure or surgery | 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 AdministrationAncillary studies | Other | 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) |
Primary outcome
Determine the feasibility of completing serial cerebrospinal fluid (CSF) collections for pharmacodynamic analyses.
Time frame: Up to 3 months
Successful collection of at least 1cc of CSF at each of 3 timepoints with successful quantification of glutamate and lactate from each sample.
1 secondary outcome
Incidence of treatment emergent adverse events (AEs) related to oxaloacetate following brain radiation (Arms B and Future Arms)
Time frame: Up to 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2025.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terence C. Burns, MD, PhD principal investigator
Mayo Clinic in Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anhydrous Enol-oxaloacetate, Best Practice and Biospecimen Collection in people with Malignant Central Nervous System Neoplasm, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 22 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine the feasibility of completing serial cerebrospinal fluid (CSF) collections for pharmacodynamic analyses. (time frame: Up to 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2025.