Trial Title:
Pharmacodynamic Analyses of Metabolic Agents Following Brain Radiation
NCT ID:
NCT05720624
Condition:
Malignant Central Nervous System Neoplasm
Conditions: Official terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Basic Science
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Anhydrous Enol-oxaloacetate
Description:
Given PO
Arm group label:
Cohort I, Arm B ( standard of care therapy, AEO)
Arm group label:
Cohort II, Arm B (standard of care therapy, AEO)
Other name:
AEO
Other name:
OXALOACETIC ACID
Intervention type:
Other
Intervention name:
Best Practice
Description:
Receive standard of care therapy
Arm group label:
Cohort I, Arm A (standard of care therapy)
Arm group label:
Cohort I, Arm B ( standard of care therapy, AEO)
Arm group label:
Cohort II, Arm A (standard of care therapy)
Arm group label:
Cohort II, Arm B (standard of care therapy, AEO)
Other name:
standard of care
Other name:
standard therapy
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of CSF and blood
Arm group label:
Cohort I, Arm A (standard of care therapy)
Arm group label:
Cohort I, Arm B ( standard of care therapy, AEO)
Arm group label:
Cohort II, Arm A (standard of care therapy)
Arm group label:
Cohort II, Arm B (standard of care therapy, AEO)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Spectroscopic Imaging
Description:
Undergo MRS imaging
Arm group label:
Cohort I, Arm A (standard of care therapy)
Arm group label:
Cohort I, Arm B ( standard of care therapy, AEO)
Arm group label:
Cohort II, Arm A (standard of care therapy)
Arm group label:
Cohort II, Arm B (standard of care therapy, AEO)
Other name:
1H- Nuclear Magnetic Resonance Spectroscopic Imaging
Other name:
1H-nuclear magnetic resonance spectroscopic imaging
Other name:
Magnetic Resonance Spectroscopy
Other name:
MRS
Other name:
MRS Imaging
Other name:
MRSI
Other name:
MS
Other name:
Proton Magnetic Resonance Spectroscopic Imaging
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Cohort I, Arm A (standard of care therapy)
Arm group label:
Cohort I, Arm B ( standard of care therapy, AEO)
Arm group label:
Cohort II, Arm A (standard of care therapy)
Arm group label:
Cohort II, Arm B (standard of care therapy, AEO)
Summary:
This phase I trial studies the impact of taking drugs (agents) that target altered brain
metabolism following standard of care brain radiotherapy. Radiotherapy uses high energy
x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. However,
radiotherapy can also cause harmful effects to normal brain functioning. One drug, called
anhydrous enol-oxaloacetate (AEO), has previously been studied in ischemic stroke,
Alzheimer's disease, Parkinson's disease, and glioma. Drugs such as AEO may help preserve
or restore healthy brain function after brain radiotherapy compared to the standard
practice which consists of no drugs.
Detailed description:
PRIMARY OBJECTIVE:
I. Determine the feasibility of serial cerebrospinal fluid (CSF) assessments to evaluate
the pharmacodynamic impact of agents targeting radiation-induced biology administered
following completion of brain radiation.
SECONDARY OBJECTIVE:
I. Assess the safety of study drug(s) as quantified by dose-limiting toxicities.
CORRELATIVE RESEARCH OBJECTIVES:
I. Investigate the relationship of the global CSF metabolome with magnetic resonance
spectroscopy metabolite profile.
II. Investigate the relationship between brain radiation dose/volume and metabolic
alterations in CSF.
III. Investigate the impact of metabolic therapy on early cognitive effects of
radiotherapy in patients with brain tumors.
IV. Utilize paired blood samples to investigate association between the CSF and systemic
metabolome.
V. Utilize paired stool samples to investigate association between the blood and CSF
metabolome with the gastrointestinal microbiome.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I (EARLY POST-RADIATION): Patients within Cohort I are assigned to 1 of 2 arms.
ARM A: Patients receive standard of care therapy.
ARM B: Patients receive standard of care therapy and receive AEO orally (PO) two times
daily (BID) for 1 month on study.
COHORT II (DELAYED POST-RADIATION): Patients within Cohort II are assigned to 1 of 2
arms.
ARM A: Patients receive standard of care therapy.
ARM B: Patients receive standard of care therapy and receive AEO PO BID for 3 months on
study.
Patients in all cohorts and arms also undergo magnetic resonance spectroscopy (MRS)
imaging, collection of cerebrospinal fluid (CSF), and collection of blood on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years.
- Radiographic evidence or histopathologic confirmation of central nervous system
(CNS) malignancy, with or without prior resection.
- Planned (cohort 1) or completed (cohort 2) fractionated brain radiation. The
therapeutic brain radiation treatment volume should exceed 30 cubic cm, including
the volume of brain tissue occupied by infiltrative disease. Volume occupied by
solid non-infiltrative disease (e.g. meningioma, metastatic disease, cystic cavity,
resection cavity), should be excluded from the estimated treatment volume.
- Provide written informed consent for the current study and the Neuro-oncology
biorepository for archiving of CSF and blood samples collected on this protocol.
- Expected survival >6 months and Karnofsky performance status >= 60.
- Willing and able to adhere with the protocol for the duration of the study including
undergoing treatment and scheduled visits, and examinations.
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) <3 x upper limit of
normal (ULN) (=< 5 x ULN for patients with baseline liver disease).
- Serum creatinine =< 1.5 mg/dL.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Willingness to provide mandatory CSF and blood and able to undergo magnetic
resonance spectroscopy (MRS)/magnetic resonance imaging (MRI) with gadolinium.
- 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
(Arm B only) until 90 days after the last dose of study drug.
Exclusion Criteria:
- Uncontrolled and/or intercurrent illness which limits safety of or compliance to
study proceedings.
- Vulnerable populations: pregnant or nursing women (Arm B exempt), prisoners,
mentally handicapped.
- Patients with recurrent brain tumor after prior radiation.
- Cohort 1 only: History of prior brain radiation, with prior cumulative target
radiation treatment volume exceeding 2 cubic centimeters.
- Patients who do not have an implanted CSF access device (who would thus require
multiple lumbar punctures [LPs] for participation) should be excluded if they have
any contra-indication to lumbar puncture. This includes but is not limited to
obstructive hydrocephalus or posterior fossa mass or cerebral edema that could
increase the risk of brain herniation.
- Patients who do not have an implanted CSF device and are on anti-platelet therapy
(other than Aspirin which is considered low risk) or anticoagulation (coumadin,
Eliquis) must discontinue these prior to each lumbar puncture to participate.
Patients unwilling or unable to safely do so should not be enrolled.
- Participants who are unable to swallow tablets or who are at risk for impaired
absorption of oral medication. NOTE: This includes but not limited to, refractory
vomiting, gastric resection/bypass, and duodenal/jejunal resection.
- Patients with recent (<3 months [mo]) administration of, or known hypersensitivity
or allergy to any active study drug currently available for randomization (initially
oxaloacetate).
- Current use of resveratrol, CoQ10 (coenzyme Q10), coconut oil/other medium chain
triglyceride-containing (i.e. Axona) supplements, or curcumin will be excluded
unless willing to discontinue them 14 days prior to the start of baseline visits and
remain off for study duration.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Terence C. Burns, M.D., Ph.D.
Email:
Principal Investigator
Start date:
March 2025
Completion date:
December 15, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05720624
https://www.mayo.edu/research/clinical-trials
