What is the mechanism of action of this treatment?

Eflornithine (DFMO) and AMXT-1501 dicaprate target polyamine metabolism, which is essential for tumor growth. DFMO inhibits ornithine decarboxylase, reducing polyamine synthesis within tumor cells, while AMXT-1501 dicaprate blocks polyamine uptake from the extracellular environment. This dual inhibition aims to starve tumor cells of necessary growth molecules, potentially slowing or stopping tumor progression. This targeted approach is significant for brain tumor patients as it may offer more effective and less toxic treatment options compared to conventional therapies.

What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as gliomas, include chemotherapy agents like temozolomide and radiation therapy. Temozolomide is associated with side effects such as myelosuppression (including thrombocytopenia and neutropenia), gastrointestinal disturbances, fatigue, and potential long-term risks like secondary hematological malignancies. Radiation therapy can cause acute side effects like fatigue, hair loss, and skin changes, as well as long-term effects such as cognitive decline and radiation necrosis. For treatments similar to Eflornithine (DFMO) and AMXT-1501 dicaprate, which target polyamine synthesis and transport, specific side effects are not well-documented, but potential side effects could include gastrointestinal issues, hematological changes, and metabolic disturbances.

What prior FDA approvals exist?

The FDA has approved several treatments for brain tumors, particularly glioblastomas. Temozolomide, an oral alkylating agent, is commonly used in combination with radiation therapy for newly diagnosed glioblastoma. Bevacizumab, an anti-VEGF monoclonal antibody, is approved for recurrent glioblastoma. While specific FDA approvals for treatments targeting ornithine decarboxylase inhibition and polyamine transport inhibition, like eflornithine (DFMO) and AMXT-1501 dicaprate, are not detailed, these mechanisms represent a novel approach in brain tumor therapy, currently under investigation in clinical trials.

What other types of research exist?

Promising novel alternatives for brain tumor treatment in 2024 include: 1) Infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, which has shown efficacy in patients with FGFR2 gene fusion or rearrangement in cholangiocarcinoma and may have potential in brain tumors with similar genetic profiles. 2) Futibatinib, another FGFR inhibitor, which has received accelerated approval for cholangiocarcinoma and could be explored for brain tumors with FGFR alterations. 3) Temozolomide-based chemoradiation therapy, which continues to be a cornerstone for high-risk low-grade gliomas and may be combined with novel agents for enhanced efficacy. These alternatives represent targeted and combination approaches that could offer new hope for brain tumor patients.

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Polyamine Transport Inhibitor

DFMO + AMXT 1501 for Brain Tumor

Phase < 1

Recruiting

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

Research Sponsored by Mayo Clinic

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 months

Summary

This trial studies how two drugs, DFMO and AMXT 1501, affect brain tumors in patients with aggressive brain tumors. DFMO stops the production of growth molecules, and AMXT 1501 blocks their intake. The goal is to see if these drugs can effectively starve the tumor.

Who is the study for?

This trial is for adults with diffuse or high-grade glioma who can swallow tablets, are not pregnant, and have no allergies to the drugs being tested. They must have proper kidney function, normal blood counts, stable thyroid function, and be able to stay in the hospital for additional days post-surgery.

What is being tested?

The study investigates how DFMO (a drug that blocks tumor growth molecules) and AMXT 1501 (which stops tumors from getting these molecules from outside) affect brain tumor metabolism. Participants will undergo surgery, imaging tests like CT/MRI scans, biospecimen collection, and microdialysis.

What are the potential side effects?

Potential side effects may include digestive issues due to oral medication intake; however specific side effects of DFMO and AMXT 1501 are not detailed here but could involve reactions similar to other chemotherapy agents such as fatigue or nausea.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in the tumor/brain extracellular guanidinoacetate ratio

Secondary study objectives

AMXT 1501 brain/plasma ratio over time

Central nervous system free drug levels from microdialysate - AMXT 1501

Central nervous system free drug levels from microdialysate - DFMO

+3 more

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Arm I (MRI, resection, DFMO, AMXT 1501)Experimental Treatment8 Interventions

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 II: Arm III (MRI, resection, DMFO, AMXT 1501)Active Control8 Interventions

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 III: Arm II (MRI, resection, placebo, DMFO, AMXT 1501)Placebo Group8 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Eflornithine

1998

Completed Phase 3

~920

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Resection

2020

Completed Phase 2

~1440

Microdialysis

2013

Completed Early Phase 1

~350

Placement

2009

Completed Phase 2

~30

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Eflornithine (DFMO) and AMXT-1501 dicaprate target polyamine metabolism, which is essential for tumor growth. DFMO inhibits ornithine decarboxylase, reducing polyamine synthesis within tumor cells, while AMXT-1501 dicaprate blocks polyamine uptake from the extracellular environment. This dual inhibition aims to starve tumor cells of necessary growth molecules, potentially slowing or stopping tumor progression. This targeted approach is significant for brain tumor patients as it may offer more effective and less toxic treatment options compared to conventional therapies.

Coagulation proteases and neurotransmitters in pathogenicity of glioblastoma multiforme.Inhibition of NF-κB signaling ablates the invasive phenotype of glioblastoma.Inhibition of thromboxane synthase activity improves glioblastoma response to alkylation chemotherapy.