Trial Title:
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
NCT ID:
NCT05717153
Condition:
Diffuse Glioma
Malignant Glioma
Conditions: Official terms:
Glioma
Eflornithine
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Basic Science
Masking:
Triple (Participant, Care Provider, Investigator)
Masking description:
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.
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Eflornithine
Description:
Given PO
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
Alpha-Difluoromethylornithine
Other name:
DFMO
Other name:
Difluoromethylornithine
Other name:
Difluromethylornithine
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Drug
Intervention name:
Polyamine Transport Inhibitor AMXT-1501 Dicaprate
Description:
Given PO
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
AMX 513 Dicaprate
Other name:
AMX513 Dicaprate
Other name:
AMXT 1501 Dicaprate
Other name:
AMXT-1501 Dicaprate
Intervention type:
Procedure
Intervention name:
Resection
Description:
Undergo surgical resection
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
Surgical Resection
Intervention type:
Device
Intervention name:
Microdialysis
Description:
Undergo Microdialysis
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Intervention type:
Procedure
Intervention name:
Placement
Description:
Undergo placement of catheters
Arm group label:
Arm I (MRI, resection, DFMO, AMXT 1501)
Arm group label:
Arm II (MRI, resection, placebo, DMFO, AMXT 1501)
Arm group label:
Arm III (MRI, resection, DMFO, AMXT 1501)
Other name:
Place
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.
Criteria for eligibility:
Criteria:
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 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/ partial thromboplastin time (aPTT/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
- 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
Exclusion Criteria:
- Patients who are not appropriate 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
- Participants who are 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
- Patients with known hypersensitivity or allergy to DFMO or AMXT 1501
- Contraindication to MRI or administration of gadolinium
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Terence C. Burns, M.D., Ph.D.
Email:
Principal Investigator
Start date:
October 1, 2023
Completion date:
September 15, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05717153
https://www.mayo.edu/research/clinical-trials
