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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Anhydrous Enol-oxaloacetate for brain cancer?

Research shows that oxaloacetate, a component of the treatment, can help reduce tumor size and increase survival in animal models of brain cancer by lowering blood glutamate levels, which are linked to tumor growth. ^{1 2 3 4 5}

Is oxaloacetate safe for use in humans?

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 mice with brain tumors. ^{3 4 5 6 7}

How does the drug dichloroacetate differ from other treatments for brain cancer after radiotherapy?

Dichloroacetate (DCA) is unique because it targets the metabolism of cancer cells by activating mitochondrial oxidative metabolism, which can help reverse the increased glycolysis (sugar breakdown) that often makes tumors resistant to radiotherapy. This approach not only enhances the effectiveness of radiotherapy but also exploits the altered metabolic state of tumor cells, potentially improving outcomes for patients with recurrent malignant brain tumors. ^{1 2 4 5 8}

Research Team

Terence C. Burns, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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.

I am 18 years old or older.

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

Exclusion Criteria

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Radiation Induced Metabolic Alterations Associate With Tumor Aggressiveness and Poor Outcome in Glioblastoma. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Selective activity of phenylacetate against malignant gliomas: resemblance to fetal brain damage in phenylketonuria. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Metabolic substrate utilization by tumour and host tissues in cancer cachexia. [2019]