Trial of AEO in New Glioblastoma (GBM)

Phase 2

• Conditions: Glioblastoma Multiforme
• Interventions: Other: Standard of Care; Drug: Anhydrous Enol-Oxaloacetate (AEO)

• Registration Number: NCT04450160
• Lead Sponsor: MetVital, Inc.

Brief Summary

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

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.

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Study Timeline

• Status Verified: 2020-06
• Study First Submitted: 2020-06-23
• Study First Submitted QC: 2020-06-25
• Last Update Submitted: 2020-06-25
• Study First Posted: 2020-06-29
• Last Update Posted: 2020-06-29
• Study Start: 2020-12
• Primary Completion: 2022-07
• Study Completion: 2022-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide.
AEO with Standard of Care	Anhydrous Enol-Oxaloacetate (AEO)	Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide).
AEO with Standard of Care	Standard of Care	Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide).

Primary Outcome Measures

Name	Time	Method
Overall Survival	6 months	Measurement of Overall Survival
Progression Free Survival-6	6 months	Survival at 6 months

Secondary Outcome Measures

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