Metabolic Agents After Brain Radiotherapy for Brain Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Resveratrol, CoQ10, Curcumin, others

Disqualifiers: Pregnancy, Recurrent brain tumor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a drug called anhydrous enol-oxaloacetate (AEO) can maintain brain health after standard brain cancer radiation therapy. Radiation can harm normal brain cells, so researchers seek to discover if AEO can repair or prevent this damage. Participants will receive either standard care alone or standard care plus AEO to compare outcomes. This trial may suit individuals diagnosed with brain cancer who are planning to undergo, or have just completed, brain radiation therapy. As a Phase 1 trial, this research focuses on understanding how AEO works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires you to stop taking resveratrol, CoQ10, coconut oil, or curcumin at least 14 days before starting and throughout the study. If you are on anti-platelet therapy (except low-risk Aspirin) or anticoagulation, you must stop these before each lumbar puncture if you don't have an implanted CSF device.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that anhydrous enol-oxaloacetate (AEO) has been tested in conditions like Alzheimer's disease and brain tumors. In these studies, patients who took 1000 mg of AEO twice a day for one month found it safe, with no significant changes in vital signs, indicating no serious health issues. The treatment also interacted positively with brain energy processes, suggesting beneficial effects.

Additionally, animal studies on brain cancer have shown no harmful effects from AEO. The FDA has granted AEO a Fast Track designation, indicating that early evidence suggests it could be a promising and safe treatment option.

Overall, while this trial is in the early stages, past research on AEO in other conditions suggests it might be well-tolerated in humans. However, as with any new treatment, monitoring for side effects is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, which typically involve chemotherapy, radiation, and surgery, Anhydrous Enol-oxaloacetate (AEO) offers a novel approach by potentially altering the cancer's metabolism. This compound aims to starve cancer cells by interfering with their energy production pathways. Researchers are excited about AEO because it targets the metabolic processes of cancer cells directly, which could lead to more effective treatment outcomes with possibly fewer side effects. Additionally, AEO is administered orally, which might simplify the treatment process compared to more invasive standard options.

What evidence suggests that this trial's treatments could be effective for brain cancer?

Research shows that anhydrous enol-oxaloacetate (AEO) might improve brain health after radiation treatment for brain cancer. In animal studies, AEO proved safe and even extended the lifespan of rats. It alters how cancer cells use energy, potentially slowing their growth. Additionally, AEO has shrunk tumors in animal studies. In this trial, some participants will receive standard care therapy with AEO, while others will receive only the standard care. Although still in early stages, these findings suggest that AEO could protect or restore brain function after radiation therapy. ^{4 5 6 7 8}

Who Is on the Research Team?

Terence C. Burns, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with brain tumors who've had or will have brain radiation, can swallow tablets, and are expected to live more than 6 months. They must be able to do questionnaires and agree to use dual contraception if of childbearing potential. Excluded are those with recent allergies to study drugs, uncontrolled illnesses affecting safety or compliance, pregnant/nursing women (except Arm B), prisoners, mentally handicapped individuals.

Inclusion Criteria

I am willing to give samples and can have an MRI with contrast.

ALT and AST levels <3 x upper limit of normal (=< 5 x ULN for patients with baseline liver disease)

My doctor expects me to live more than 6 months and I can care for myself.

Exclusion Criteria

I am on blood thinners but do not have a CSF device implanted.

Vulnerable populations: pregnant or nursing women (Arm B exempt), prisoners, mentally handicapped

I do not have any illnesses that would make it unsafe for me to participate in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants undergo standard of care brain radiotherapy

Varies

Treatment

Participants receive standard of care therapy and may receive AEO orally two times daily

1-3 months

Regular visits for MRS imaging, CSF, and blood collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Anhydrous Enol-oxaloacetate

Trial Overview This trial tests the drug anhydrous enol-oxaloacetate (AEO) on patients after standard brain radiotherapy for nervous system tumors. It compares AEO's ability to preserve healthy brain function against the usual practice without drugs. Participants will also undergo MR spectroscopic imaging and provide biospecimens.

How Is the Trial Designed?

Group I: Cohort II, Arm B (standard of care therapy, AEO) Experimental Treatment 5 Interventions

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.

Group II: Cohort I, Arm B ( standard of care therapy, AEO) Experimental Treatment 5 Interventions

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.

Group III: Cohort I, Arm A (standard of care therapy) Active Control 4 Interventions

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.

Group IV: Cohort II, Arm A (standard of care therapy) Active Control 4 Interventions

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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10722244/

Oxaloacetate as a Holy Grail Adjunctive Treatment in Gliomas Studies revealed that OAA supplementation reduced Warburg glycolysis, improved neuronal cell bioenergetics, and triggered brain mitochondrial ...

2. withpower.com withpower.com/trial/phase-1-nervous-system-neoplasms-1-2023-f786a

Metabolic Agents After Brain Radiotherapy for Brain Cancer Research on oxaloacetate, used in animal studies for brain cancer, suggests it may be safe, as it showed no apparent toxicity and prolonged survival in rats and ...

3. targetedonc.com targetedonc.com/view/fda-grants-fast-track-designation-to-novel-molecule-to-treat-glioblastoma

FDA Grants Fast Track Designation to Novel Molecule ... AEO turns into oxaloacetate in the body, which has been found to alter cancer metabolism in glioblastoma cells, reducing glycolysis and lactate ...

4. clinconnect.io clinconnect.io/trials/NCT05720624

Pharmacodynamic Analyses of Metabolic Agents Following The study aims to see if taking AEO after standard radiation treatment can help protect or improve brain health compared to not taking any medication. This ...

5. researchgate.net researchgate.net/publication/350385387_FSMP-02_CHANGES_IN_GLUTAMINE_METABOLISM_INDUCED_BY_OXALOACETATE_IN_GLIOBLASTOMA

fsmp-02. changes in glutamine metabolism induced by ... Anhydrous Enol-Oxaloacetate (AEO) has been shown to significantly increase survival and decrease tumor growth rates in animal models of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8084114/

Safety and target engagement profile of two oxaloacetate ... 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism. Keywords: Alzheimer's disease, bioenergetics, metabolism ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04290897

Study Details | NCT04290897 | Oxaloacetate for the ... Giving oxaloacetate may reduce inflammation in the brain that could be contributing to cognitive complaints seen after cancer treatments. Detailed Description.

8. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1483876/full

RESTORE ME: a RCT of oxaloacetate for improving fatigue ... Our primary endpoints in the trial were safety and the reduction of fatigue. There were no remarkable changes in vital signs between the two ...