Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma

NCT05717153 | Recruiting Early Phase 1 DMC FDA Drug FDA Device

• 3 other identifiers: 22-005690NCI-2022-10375R37CA276851
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diffuse Glioma; Malignant Glioma

Outcome Measures

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.

  Baseline up to 2 months

Secondary Outcomes (6)

• Measured extracellular levels of glutamate in tumor and brain microdialysates

  Up to 2 months

• Proportion of longitudinal microdialysis aliquots containing > 30 uL of microdialysate

  Up to post-operative day 5

• Central nervous system free drug levels from microdialysate - DFMO

  Up to 2 months

• Central nervous system free drug levels from microdialysate - AMXT 1501

  Up to 2 months

• AMXT 1501 brain/plasma ratio over time

  Up to 2 months

Study Arms (3)

Arm I (MRI, resection, DFMO, AMXT 1501)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Eflornithine; Procedure: Magnetic Resonance Imaging; Drug: Polyamine Transport Inhibitor AMXT-1501 Dicaprate; Procedure: Resection; Device: Microdialysis; Procedure: Placement

Arm II (MRI, resection, placebo, DMFO, AMXT 1501)

PLACEBO COMPARATOR

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Eflornithine; Procedure: Magnetic Resonance Imaging; Drug: Polyamine Transport Inhibitor AMXT-1501 Dicaprate; Procedure: Resection; Device: Microdialysis; Procedure: Placement

Arm III (MRI, resection, DMFO, AMXT 1501)

ACTIVE COMPARATOR

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.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Eflornithine; Procedure: Magnetic Resonance Imaging; Drug: Polyamine Transport Inhibitor AMXT-1501 Dicaprate; Procedure: Resection; Device: Microdialysis; Procedure: Placement

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Eflornithine DRUG

Given PO

Also known as: Alpha-Difluoromethylornithine, DFMO, Difluoromethylornithine, Difluromethylornithine

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Polyamine Transport Inhibitor AMXT-1501 Dicaprate DRUG

Given PO

Also known as: AMX 513 Dicaprate, AMX513 Dicaprate, AMXT 1501 Dicaprate, AMXT-1501 Dicaprate

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Microdialysis DEVICE

Undergo Microdialysis

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Placement PROCEDURE

Undergo placement of catheters

Also known as: Place

Arm I (MRI, resection, DFMO, AMXT 1501); Arm II (MRI, resection, placebo, DMFO, AMXT 1501); Arm III (MRI, resection, DMFO, AMXT 1501)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 or partial thromboplastin time (aPTT or 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 \[Thyroid Stimulating Hormone (TSH)\]
• 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 \< 14 days prior to registration

You may not qualify if:

• 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
• Contraindication to MRI or administration of gadolinium

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Glioma

Interventions

Specimen Handling; Eflornithine; Magnetic Resonance Spectroscopy; Microdialysis; Drug Implants

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Spectrum Analysis; Chemistry Techniques, Analytical; Dialysis; Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Terence C. Burns, MD, PhD

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The patient and the principal investigator will be blinded to each patient's assignment until after the catheter has been placed. However, the clinical research coordinators and co-investigators will remain unblinded to facilitate study coordination and ensure protocol adherence.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2023
• First Posted: February 8, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): September 15, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-10

Locations

US (1)