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

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Diffuse Glioma
• Malignant Glioma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Eflornithine	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Polyamine Transport Inhibitor AMXT-1501 Dicaprate	Given PO
PROCEDURE	Resection	Undergo surgical resection
DEVICE	Microdialysis	Undergo Microdialysis
PROCEDURE	Placement	Undergo placement of catheters

Timeline

• Start date: 2023-10-01
• Primary completion: 2027-01-15
• Completion: 2027-09-15
• First posted: 2023-02-08
• Last updated: 2025-11-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study