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

Primary Purpose

Glioblastoma Multiforme

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Anhydrous Enol-Oxaloacetate (AEO)
Standard of Care
Sponsored by
MetVital, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma, Oxaloacetate, Seizures, Warburg

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Placebo Comparator

    Experimental

    Arm Label

    Standard of Care

    AEO with Standard of Care

    Arm Description

    Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide.

    Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide).

    Outcomes

    Primary Outcome Measures

    Overall Survival
    Measurement of Overall Survival
    Progression Free Survival-6
    Survival at 6 months

    Secondary Outcome Measures

    Seizures
    Time from randomization to first seizure
    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
    PROMIS-Cancer - Fatigue
    Measure of Fatigue Ranging from a minimum of 0 to a maximum of 95 with the higher score indicating worse outcome.

    Full Information

    First Posted
    June 23, 2020
    Last Updated
    June 25, 2020
    Sponsor
    MetVital, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04450160
    Brief Title
    Trial of AEO in New Glioblastoma (GBM)
    Acronym
    AEO
    Official Title
    A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    December 2020 (Anticipated)
    Primary Completion Date
    July 2022 (Anticipated)
    Study Completion Date
    September 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    MetVital, Inc.

    4. Oversight

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

    5. 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.
    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. .

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Glioblastoma Multiforme
    Keywords
    Glioblastoma, Oxaloacetate, Seizures, Warburg

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    80 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Standard of Care
    Arm Type
    Placebo Comparator
    Arm Description
    Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide.
    Arm Title
    AEO with Standard of Care
    Arm Type
    Experimental
    Arm Description
    Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide).
    Intervention Type
    Drug
    Intervention Name(s)
    Anhydrous Enol-Oxaloacetate (AEO)
    Intervention Description
    Oral supplementation with AEO along with the Standard of Care (Temozolomide)
    Intervention Type
    Other
    Intervention Name(s)
    Standard of Care
    Other Intervention Name(s)
    Chemotherapy with Temozolomide
    Intervention Description
    Standard of Care Temozolomide
    Primary Outcome Measure Information:
    Title
    Overall Survival
    Description
    Measurement of Overall Survival
    Time Frame
    6 months
    Title
    Progression Free Survival-6
    Description
    Survival at 6 months
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Seizures
    Description
    Time from randomization to first seizure
    Time Frame
    6 months
    Title
    Chalfont-National Hospital Seizure Severity
    Description
    Measure of Seizure Severity Ranging from a minimum of 1 to a maximum of 27 with higher score indicating worse outcome
    Time Frame
    6 months
    Title
    PROMIS-Cancer - Fatigue
    Description
    Measure of Fatigue Ranging from a minimum of 0 to a maximum of 95 with the higher score indicating worse outcome.
    Time Frame
    6 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Alan B Cash, MS
    Phone
    858-947-5722
    Email
    acash@MetVital.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    30349820
    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.
    Results Reference
    background
    PubMed Identifier
    22392507
    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.
    Results Reference
    background
    PubMed Identifier
    12749815
    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.
    Results Reference
    background
    Links:
    URL
    http://doi.org/10.1093/neuonc/noz175.171
    Description
    Oxaloacetate alters glucose metabolism in Glioblastoma
    URL
    http://doi.org/10.1093/neuonc/nox168.238
    Description
    Oxaloacetate increases survival in GBM implanted mice
    URL
    http://doi.org/10.1093/neuonc/noy148.1154
    Description
    New Bioanalytical method and single-dose pharmacokinetics for oxaloacetate

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    Trial of AEO in New Glioblastoma (GBM)

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