Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic
About this trial
This early phase I trial studies brain tumor (glioma) metabolism in response to eflornithine (DFMO) and polyamine transport inhibitor AMXT-1501 dicaprate (AMXT 1501) in patients with diffused or high grade glioma. Brain tumors use and produce certain molecules to survive and grow. DFMO is an irreversible inhibitor of ornithine decarboxylase, the enzyme catalyzing polyamine synthesis. AMXT 1501 is a polyamine transport inhibitor which prevents uptake of polyamines from the extracellular environment. This trial is being done to analyze how DFMO and AMXT 1501 affect brain tumor metabolism based on the molecules in the tumor's fluid.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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 or biopsy 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
Disqualifiers
Inappropriate 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
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
Known hypersensitivity or allergy to DFMO or AMXT 1501
Trial design
Design model
Parallel
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood
Computed Tomography
Procedure/SurgeryUndergo CT
Eflornithine
DrugGiven PO
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Polyamine Transport Inhibitor AMXT-1501 Dicaprate
DrugGiven PO
Resection
Procedure/SurgeryUndergo surgical resection
Microdialysis
DeviceUndergo Microdialysis
Placement
Procedure/SurgeryUndergo placement of catheters
Treatment groups
18 Participants
are divided into 3 treatment groupsGroup A: Arm I (MRI, resection, DFMO, AMXT 1501)Experimental treatment 8 interventions
Group B: Arm II (MRI, resection, placebo, DMFO, AMXT 1501)Placebo comparator 8 interventions
Group C: Arm III (MRI, resection, DMFO, AMXT 1501)Active comparator 8 interventions
Trial outcomes
Primary outcomes
1
Change in the tumor/brain extracellular guanidinoacetate ratio
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.
Time frame
Baseline up to 2 monthsSecondary outcomes
1
Measured extracellular levels of glutamate in tumor and brain microdialysates
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.
Time frame
Up to 2 months2
Proportion of longitudinal microdialysis aliquots containing > 30 uL of microdialysate
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.
Time frame
Up to post-operative day 53
Central nervous system free drug levels from microdialysate - DFMO
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).
Time frame
Up to 2 months4
Central nervous system free drug levels from microdialysate - AMXT 1501
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).
Time frame
Up to 2 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Mayo Clinic
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Source ClinicalTrials.gov