- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05717153
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
I. Determine how polyamine depletion impacts extracellular guanidinoacetate abundance.
SECONDARY OBJECTIVES:
I. Determine the impact of polyamine depletion on polyamine abundance and the global extracellular metabolome within live human gliomas, in situ.
II. Assess the feasibility of longitudinal microdialysis to evaluate pharmacodynamic responses of in situ gliomas to therapeutic intervention in a post-operative setting.
III. Assess the central nervous system (CNS) pharmacokinetics of DFMO and AMXT 1501.
IV. Adverse effects of study drugs in the immediate postoperative setting during microdialysis.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I: Patients undergo surgical resection with magnetic resonance imaging (MRI) and placement of catheters for microdialysis at baseline. Patients receive DFMO orally (PO) in combination with AMXT 1501 PO on days 1-5 post-surgery in the absence of disease progression or unacceptable toxicity. Patients also continue microdialysate collection as well as undergo computed tomography (CT) and collection of blood on study.
ARM II: Patients undergo surgical resection with MRI and placement of catheters for microdialysis at baseline. Patients receive DFMO PO and AMXT 1501 PO on days 3-5 post-surgery in the absence of disease progression or unacceptable toxicity. Patients also continue microdialysate collection, as well as undergo CT and collection of blood on study.
ARM III: Patients undergo surgical resection with MRI and placement of catheters for microdialysis at baseline. Patients receive DFMO PO alone on days 1 and 2 post-surgery, then receive eflornithine PO in combination with AMXT 1501 PO on days 3-5 post-surgery in the absence of disease progression or unacceptable toxicity. Patients also continue microdialysate collection, as well as undergo CT and collection of blood on study.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic in Rochester
-
Contact:
- Clinical Trials Referral Office
- Phone Number: 855-776-0015
- Email: mayocliniccancerstudies@mayo.edu
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Principal Investigator:
- Terence C. Burns, M.D., Ph.D.
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age >= 18 years
- Clinical and radiographic evidence suggesting a diagnosis of a diffuse high grade glioma (HGG), or a prior diagnosis of a diffuse glioma
- Planned subtotal resection due to tumor location, size, or other clinical indication deemed appropriate by the surgeon
- Provide written informed consent for the current study and the Neuro-Oncology biorepository for archiving of cerebrospinal fluid (CSF) and blood samples collected on this protocol. Willing to remain in the hospital at Mayo Clinic (Rochester, MN) for three days added to their standard post-operative stay to undergo longitudinal microdialysis
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without transfusion within 7 days preceding the lab assessment (obtained =< 14 days prior to registration)
- Platelet >= 100 x 10^9/L, without transfusion within 7 days preceding the lab assessment (obtained =< 14 days prior to registration)
- Hemoglobin >= 9 g/dL, without transfusion support within 7 days preceding the lab assessment (obtained =< 14 days prior to registration)
- Activated partial thromboplastin time/ partial thromboplastin time (aPTT/PTT) =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (obtained =< 14 days prior to registration)
- Total serum bilirubin =< 1.5 x ULN (obtained =< 14 days prior to registration)
- The patient is clinically euthyroid
- Serum creatinine =< 1.5 x ULN or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with serum creatinine levels above 1.5 x ULN (obtained =< 14 days prior to registration)
- Negative serum or urine pregnancy test is required for female subjects of childbearing age
Exclusion Criteria:
- Patients who are not appropriate surgical candidates due to current or past medical history or uncontrolled concurrent illness which limits safety of or compliance to study proceedings
- Vulnerable populations: pregnant or nursing women, prisoners, mentally handicapped
- 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 known hypersensitivity or allergy to DFMO or AMXT 1501
- Contraindication to MRI or administration of gadolinium
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (MRI, resection, DFMO, AMXT 1501)
Patients undergo magnetic resonance imaging (MRI) and surgical resection at baseline.
Patients receive eflornithine PO in combination with AMXT 1501 PO on days 1-5 post-surgery.
Patients also undergo CT after surgery and collection of blood on study.
|
Undergo collection of blood
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Undergo surgical resection
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Undergo Microdialysis
Undergo placement of catheters
Other Names:
|
Placebo Comparator: Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Patients undergo magnetic MRI and surgical resection at baseline.
Patients receive placebo PO on days 1 and 2 post-surgery, and then receive eflornithine PO and AMXT 1501 PO on days 3-5 post-surgery.
Patients also undergo CT after surgery and collection of blood on study.
|
Undergo collection of blood
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Undergo surgical resection
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Undergo Microdialysis
Undergo placement of catheters
Other Names:
|
Active Comparator: Arm III (MRI, resection, DMFO, AMXT 1501)
Patients undergo magnetic MRI and surgical resection at baseline.
Patients receive eflornithine PO alone on days 1 and 2 post-surgery, then receive eflornithine PO in combination with AMXT 1501 PO on days 3-5 post-surgery.
Patients also undergo CT after surgery and collection of blood on study.
|
Undergo collection of blood
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Undergo surgical resection
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Undergo Microdialysis
Undergo placement of catheters
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the tumor/brain extracellular guanidinoacetate ratio
Time Frame: Baseline up to 2 months
|
Targeted metabolomics will be performed using the microdialysate aliquot collected at each time point to quantify guanidinoacetate content.
Fold change values will be calculated between each time point within a patient.
Fold changes values between time points will be compared across the three arms for statistically significant differences using a Wilcoxon signed rank test; p < 0.05 will be considered statistically significant.
|
Baseline up to 2 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measured extracellular levels of glutamate in tumor and brain microdialysates
Time Frame: Up to 2 months
|
Targeted metabolomics will be performed for each time point's microdialysate, assaying for polyamines (putrescine, spermine, and spermidine), in addition to ornithine and glutamate.
Fold change values will be calculated between each time point within a patient.
Fold changes values between time points will be compared across the three arms for statistically significant differences using a Wilcoxon signed rank test; p < 0.05 will be considered statistically significant.
|
Up to 2 months
|
Proportion of longitudinal microdialysis aliquots containing > 30 uL of microdialysate
Time Frame: Up to post-operative day 5
|
Targeted metabolomics will be performed for each time point's microdialysate, assaying for polyamines (putrescine, spermine, and spermidine), in addition to ornithine and glutamate.
Fold change values will be calculated between each time point within a patient.
Fold changes values between time points will be compared across the three arms for statistically significant differences using a Wilcoxon signed rank test; p < 0.05 will be considered statistically significant.
|
Up to post-operative day 5
|
Central nervous system free drug levels from microdialysate - DFMO
Time Frame: Up to 2 months
|
Drug levels of difluoromethylornithine (eflornithine [DFMO]) at each time point will be calculated for pharmacokinetic analyses by Aminex Therapeutics to determine time of peak concentration (hr), maximum drug concentration (ng/mL), and area under the curve 0-t (hr*ng/mL).
|
Up to 2 months
|
Central nervous system free drug levels from microdialysate - AMXT 1501
Time Frame: Up to 2 months
|
Polyamine transport inhibitor AMXT-1501 dicaprate (AMXT 1501) at each time point will be calculated for pharmacokinetic analyses by Aminex Therapeutics to determine time of peak concentration (hr), maximum drug concentration (ng/mL), and area under the curve 0-t (hr*ng/mL).
|
Up to 2 months
|
AMXT 1501 brain/plasma ratio over time
Time Frame: Up to 2 months
|
Will be assessed via longitudinal microdialysis to understand how AMXT 1501 is distributed in Central Nervous System (CNS) tissue with and without tumor as compared to plasma levels over time.
|
Up to 2 months
|
Incidence of adverse events
Time Frame: Up to 2 months
|
Although no significant additional risks are anticipated in the proposed context, safety data will be assessed to evaluate for any unanticipated adverse events.
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Up to 2 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Terence C. Burns, M.D., Ph.D., Mayo Clinic in Rochester
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Trypanocidal Agents
- Ornithine Decarboxylase Inhibitors
- Eflornithine
Other Study ID Numbers
- 22-005690 (Mayo Clinic in Rochester)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2022-10375 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- R37CA276851 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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