Malignant Glioma Clinical Trial
Official title:
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501
Verified date | January 2024 |
Source | Mayo Clinic |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Recruiting |
Enrollment | 15 |
Est. completion date | September 15, 2027 |
Est. primary completion date | January 15, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | Mayo Clinic in Rochester | Rochester | Minnesota |
Lead Sponsor | Collaborator |
---|---|
Mayo Clinic | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | Baseline up to 2 months | |
Secondary | 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. | Up to 2 months | |
Secondary | 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. | Up to post-operative day 5 | |
Secondary | 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). | Up to 2 months | |
Secondary | 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). | Up to 2 months | |
Secondary | AMXT 1501 brain/plasma ratio over time | 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 | |
Secondary | Incidence of adverse events | Although no significant additional risks are anticipated in the proposed context, safety data will be assessed to evaluate for any unanticipated adverse events. | Up to 2 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
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