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

NCT ID: NCT05717153

Last Updated: 2025-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-01

Study Completion Date

2027-09-15

Brief Summary

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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

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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

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Diffuse Glioma Malignant Glioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
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.

Study Groups

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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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Eflornithine

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Polyamine Transport Inhibitor AMXT-1501 Dicaprate

Intervention Type DRUG

Given PO

Resection

Intervention Type PROCEDURE

Undergo surgical resection

Microdialysis

Intervention Type DEVICE

Undergo Microdialysis

Placement

Intervention Type PROCEDURE

Undergo placement of catheters

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.

Group Type PLACEBO_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Eflornithine

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Polyamine Transport Inhibitor AMXT-1501 Dicaprate

Intervention Type DRUG

Given PO

Resection

Intervention Type PROCEDURE

Undergo surgical resection

Microdialysis

Intervention Type DEVICE

Undergo Microdialysis

Placement

Intervention Type PROCEDURE

Undergo placement of catheters

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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Eflornithine

Intervention Type DRUG

Given PO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Polyamine Transport Inhibitor AMXT-1501 Dicaprate

Intervention Type DRUG

Given PO

Resection

Intervention Type PROCEDURE

Undergo surgical resection

Microdialysis

Intervention Type DEVICE

Undergo Microdialysis

Placement

Intervention Type PROCEDURE

Undergo placement of catheters

Interventions

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Biospecimen Collection

Undergo collection of blood

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Eflornithine

Given PO

Intervention Type DRUG

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Polyamine Transport Inhibitor AMXT-1501 Dicaprate

Given PO

Intervention Type DRUG

Resection

Undergo surgical resection

Intervention Type PROCEDURE

Microdialysis

Undergo Microdialysis

Intervention Type DEVICE

Placement

Undergo placement of catheters

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography Alpha-Difluoromethylornithine DFMO Difluoromethylornithine Difluromethylornithine 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 AMX 513 Dicaprate AMX513 Dicaprate AMXT 1501 Dicaprate AMXT-1501 Dicaprate Surgical Resection Place

Eligibility Criteria

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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 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Terence C. Burns, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic in Rochester

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

855-776-0015

Facility Contacts

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Clinical Trials Referral Office

Role: primary

855-776-0015

Related Links

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Other Identifiers

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NCI-2022-10375

Identifier Type: REGISTRY

Identifier Source: secondary_id

R37CA276851

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22-005690

Identifier Type: -

Identifier Source: org_study_id

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