Neoplasms

All Conditions

Rare Diseases

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Eflornithine

Antiprotozoal Agents

Antiparasitic Agents

Enzyme Inhibitors

Ornithine

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.

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.

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.

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Polyamine Transport Inhibitor AMXT-1501 Dicaprate

Resection

Microdialysis

Placement

Clinical Trials Referral Office

Terence C. Burns, M.D., Ph.D.

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.

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.

The patient, principal investigator, and all members of the research team involved in sample collection will be blinded to each patient's assignment until after the catheter has been placed.

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

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.

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.

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).

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).

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.

Although no significant additional risks are anticipated in the proposed context, safety data will be assessed to evaluate for any unanticipated adverse events.

Spots Global Cancer Trial Database for placement

Every month we try and update this database with for placement cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for placement

Every month we try and update this database with for placement cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for placement cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.