Trial of AEO in New Glioblastoma (GBM) (AEO)

• ClinicalTrials.gov Identifier: NCT04450160
• Recruitment Status: Unknown
• First Posted: June 29, 2020
• Last Update Posted: June 29, 2020
• Sponsor: MetVital, Inc.
• Information provided by (Responsible Party): MetVital, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Glioblastoma Multiforme	Drug: Anhydrous Enol-Oxaloacetate (AEO); Other: Standard of Care	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme
• Estimated Study Start Date: December 2020
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: September 2022

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Standard of Care; Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide.	Other: Standard of Care; Standard of Care Temozolomide; Other Name: Chemotherapy with Temozolomide
Experimental: AEO with Standard of Care; Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide).	Drug: Anhydrous Enol-Oxaloacetate (AEO); Oral supplementation with AEO along with the Standard of Care (Temozolomide); Other: Standard of Care; Standard of Care Temozolomide; Other Name: Chemotherapy with Temozolomide

Outcome Measures

Primary Outcome Measures :

1. Overall Survival [ Time Frame: 6 months ]
   Measurement of Overall Survival
2. Progression Free Survival-6 [ Time Frame: 6 months ]
   Survival at 6 months

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Alan B Cash, MS; 858-947-5722; acash@MetVital.com

Sponsors and Collaborators

MetVital, Inc.

More Information

Additional Information:

Oxaloacetate alters glucose metabolism in Glioblastoma 

Oxaloacetate increases survival in GBM implanted mice 

New Bioanalytical method and single-dose pharmacokinetics for oxaloacetate 

Publications:

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.

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.

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.

• Responsible Party: MetVital, Inc.
• ClinicalTrials.gov Identifier: NCT04450160
• Other Study ID Numbers: Terra-001-201
• First Posted: June 29, 2020
• Last Update Posted: June 29, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by MetVital, Inc.:

Glioblastoma; Oxaloacetate; Seizures; Warburg

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents