Clinical trial NCT04450160: Trial of AEO in New Glioblastoma (GBM)
Official title: A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma
Oxaloacetate
Seizures
Warburg
Lead sponsor: MetVital, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-29
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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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Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: 6 months
measure: Progression Free Survival-6
timeFrame: 6 months
Secondary outcomes:
measure: Seizures
timeFrame: 6 months
measure: Chalfont-National Hospital Seizure Severity
timeFrame: 6 months
measure: PROMIS-Cancer - Fatigue
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
References:
citation: Augur ZM, Doyle CM, Li M, Mukherjee P, Seyfried TN. Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental Glioblastoma. Front Nutr. 2018 Oct 5;5:91. doi: 10.3389/fnut.2018.00091. eCollection 2018.
citation: Ruban A, Berkutzki T, Cooper I, Mohar B, Teichberg VI. Blood glutamate scavengers prolong the survival of rats and mice with brain-implanted gliomas. Invest New Drugs. 2012 Dec;30(6):2226-35. doi: 10.1007/s10637-012-9799-5.
citation: Yamamoto HA, Mohanan PV. Effect of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA damage and seizures induced by kainic acid in mice. Toxicol Lett. 2003 Jul 20;143(2):115-22. doi: 10.1016/s0378-4274(03)00114-0.