Glioblastoma MultiformePhase 2AEONCT04450160
Trial of AEO in New Glioblastoma (GBM)
A Phase 2 study testing Anhydrous Enol-Oxaloacetate (AEO) in people with Glioblastoma Multiforme, run by MetVital, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Anhydrous Enol-Oxaloacetate (AEO)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- Dec 2020to Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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)
Show all 13Show fewer
- <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
Who cannot join
- • 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme
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.
Read the 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.
.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Anhydrous Enol-Oxaloacetate (AEO), Standard of Care
- Keywords
- Glioblastoma, Oxaloacetate, Seizures, Warburg
- Medical subject headings
- Glioblastoma, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anhydrous Enol-Oxaloacetate (AEO)Drug
Oral supplementation with AEO along with the Standard of Care (Temozolomide)
Standard of CareOther
Also called Chemotherapy with Temozolomide
Standard of Care Temozolomide
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Placebo comparator | Current GBM Treatment of surgery, radiation and chemotherapy with temozolomide. Receives: Other: Standard of Care |
| AEO with Standard of Care | Experimental | Anhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide). Receives: Drug: Anhydrous Enol-Oxaloacetate (AEO); Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measurement of Overall Survival
Measured: 6 months
Progression Free Survival-6
Survival at 6 months
Measured: 6 months
Secondary outcomes (3)
Seizures
Time from randomization to first seizure
Measured: 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
Measured: 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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2020
- Study startDec 2020 (estimated)
- Primary completionJul 2022 (estimated)
- Study completionSep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MetVital, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04450160
- Sponsor's protocol ID
- Terra-001-201
- Acronym
- AEO
- Status last verified
- Jun 2020
- First submitted
- 23 Jun 2020
- Last updated
- 29 Jun 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 30349820Ruban 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.
PubMed 22392507Yamamoto 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.
PubMed 12749815
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Open-Label Study of Anhydrous Enol-Oxaloacetate in Subjects With Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT04450160
- Acronym / sponsor ID
- AEO / Terra-001-201
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma, Oxaloacetate, Seizures, Warburg
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- MetVital, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2020 (estimated)
- Primary completion
- Jul 2022 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 29 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Placebo comparator | Other: Standard of CareCurrent GBM Treatment of surgery, radiation and chemotherapy with temozolomide. |
| AEO with Standard of Care | Experimental | Drug: Anhydrous Enol-Oxaloacetate (AEO), Other: Standard of CareAnhydrous Enol-Oxaloacetate added to the Standard of Care (surgery, radiation and chemotherapy with temozolomide). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- • Histopathologic diagnosis of glioblastoma multiforme
Key exclusion criteria (6 listed)
- • Concomitant treatment with carmustine wafers or tumor-treating electric fields (TTFields)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anhydrous Enol-Oxaloacetate (AEO)Oral supplementation with AEO along with the Standard of Care (Temozolomide) | Drug | AEO with Standard of Care |
| Standard of CareAlso: Chemotherapy with TemozolomideStandard of Care Temozolomide | Other | AEO with Standard of Care, Standard of Care |
Primary outcome
Overall Survival
Time frame: 6 months
Measurement of Overall Survival
Progression Free Survival-6
Time frame: 6 months
Survival at 6 months
3 secondary outcomes
Seizures
Time frame: 6 months
Chalfont-National Hospital Seizure Severity
Time frame: 6 months
PROMIS-Cancer - Fatigue
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2020.
- Background: PubMed 30349820Augur 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.
- Background: PubMed 22392507Ruban 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.
- Background: PubMed 12749815Yamamoto 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.
- Oxaloacetate increases survival in GBM implanted miceLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anhydrous Enol-Oxaloacetate (AEO) in people with Glioblastoma Multiforme, run by MetVital, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alan B Cash, MS (858-947-5722, acash@MetVital.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04450160, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2020.