Trial of AEO in New Glioblastoma (GBM)

Study Overview
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Brief Summary
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This is a multicenter, Phase 2, Proof-of-concept study in subjects with newly diagnosed glioblastoma multiforme (GBM). All subjects will receive standard of care therapy for the treatment of their GBM and any Anti-Epileptic Drug (AED) deemed necessary for their surgical resection of the GBM. Patients who are taking concomitant AEDs will be eligible for the study. Treatment with Anhydrous Enol-Oxaloacetate will be added to the Standard of Care. This study is testing adjuvant Anhydrous Enol-Oxaloacetate (AEO) in GBM, an orally active drug candidate which in animal studies has demonstrated decreased tumor growth rate and increased survival.

Detailed Description
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Currently, the multidisciplinary Standard of Care treatment for Glioblastoma multiforme includes maximal surgical resection of the tumor followed by radiotherapy plus concomitant and maintenance temozolomide chemotherapy.This study will treat newly diagnosed GBM patients by adding Anhydrous Enol-Oxaloacetate treatment to their current Standard of Care. In the body, Anhydrous Enol-Oxaloacetate (AEO) converts into Oxaloacetate, a metabolite important for many biochemical reactions in the body. On a cellular level, oxaloacetate treatment has been found to modify cancer metabolism in GBM cells, reversing the Warburg Effect, reducing glycolysis and reducing lactate production. In animals, oxaloacetate treatment has increased survival and reduced tumor growth of implanted GBM tumors. In other animal studies, oxaloacetate has also shown to have neuo-protective effects including positive effects on seizure development. .

Official Title
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A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Anhydrous Enol-Oxaloacetate (AEO)
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Histopathologic diagnosis of glioblastoma multiforme Standard of care maximal feasible surgical resection of the glioma Post-operative pre-enrollment MRI-Note: measurable disease is not required Concomitant anti-epileptic drugs Hemoglobin >9 g/dL Platelets >100,000/microliter (mcL) <3.0 Upper Limit of Normal Range (ULN) for Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and/or Alkaline Phosphatase <2.0 Upper Limit of Normal Range (ULN) for serum creatinine Karnofsky performance status >70 Mentally competent to follow study procedures 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 until 90 days after the last dose of study drug Able to answer questions on the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire Subject is willing and able to give informed consent and to follow instructions as per the protocol Exclusion Criteria: • Concomitant treatment with carmustine wafers or tumor-treating electric fields (TTFields) QT Interval corrected with the fridericia formula (QTcF) >480ms Significant concurrent illness / disease Predicted life expectancy < 6 months from date of randomization Pregnancy Enrollment in another clinical trial during the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard of Care<br>Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide. | Other: Standard of Care<br>* Standard of Care Temozolomide<br>* Other names: Chemotherapy with Temozolomide;|
| Experimental: AEO with Standard of Care<br>Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide). | Drug: Anhydrous Enol-Oxaloacetate (AEO)<br>* Oral supplementation with AEO along with the Standard of Care (Temozolomide)<br>Other: Standard of Care<br>* Standard of Care Temozolomide<br>* Other names: Chemotherapy with Temozolomide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Measurement of Overall Survival | 6 months | 
| Progression Free Survival-6 | Survival at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seizures | Time from randomization to first seizure | 6 months | 
| Chalfont-National Hospital Seizure Severity | Measure of Seizure Severity Ranging from a minimum of 1 to a maximum of 27 with higher score indicating worse outcome | 6 months | 
| PROMIS-Cancer - Fatigue | Measure of Fatigue Ranging from a minimum of 0 to a maximum of 95 with the higher score indicating worse outcome. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Oxaloacetate, Seizures, Warburg