Glioblastoma Multiforme Clinical Trial
Official title:
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma
NCT number | NCT04530006 |
Other study ID # | 50604 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | December 2, 2020 |
Est. completion date | August 2025 |
Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The strikingly poor survival for patients with GBM (average survival 14-16 months following diagnosis) is due in part to limited early detection methods and an absence of effective therapeutic options. The study proposed would establish important evidence for the use of Health Canada approved drugs such as amantadine as a safe, effective and affordable way to monitor GBM. The method is based on the overproduction of a key enzyme in GBM cells called spermine/ spermidine n-acetyl transferase (SSAT1). The increased SSAT1 expression in GBM results in increased metabolism of the drug which is detected in the blood or urine of patients with GBM. The levels of acetyl-amantadine captured will be correlated with the tumor burden as seen on the MRIs of these patients. Thus, the study aims to determine the usefulness of amantadine as a diagnostic biomarker for GBM.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | August 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Adult (18 years+) - Pathologically confirmed Glioblastoma - ECOG performance status 0-2 - Planned treatment with radiation and/or chemotherapy with temozolomide or lomustine - Able to return to the study centre for study visits - Able to swallow oral pills - Serum creatinine and creatinine clearance (>60mL/min) - Liver enzymes for liver function (Liver function tests <2.5 times the upper limit of normal) - Participants of childbearing potential must agree to use an effective contraceptive method. Exclusion Criteria: - Known hypersensitivity or allergy to amantadine - Concurrent infection requiring antiviral medication - Concurrent medication with known interaction with amantadine (see below) - Previous diagnosis of Parkinson's disease or parkinsonism - Previous diagnosis of schizophrenia - Current use of methamphetamine or cocaine - Inability to swallow oral pills - Significant impairment in renal function (Creatinine clearance < 60 mL/min) - Women who are pregnant or are breastfeeding |
Country | Name | City | State |
---|---|---|---|
Canada | CancerCare Manitoba | Winnipeg | Manitoba |
Lead Sponsor | Collaborator |
---|---|
CancerCare Manitoba | BioMark Diagnostics Inc., Canadian Institutes of Health Research (CIHR), The Metabolomics Innovation Centre, University of Manitoba |
Canada,
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Gabrielson E, Tully E, Hacker A, Pegg AE, Davidson NE, Casero RA Jr. Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1, N11-diethylnorspermine. Cancer Chemother Pharmacol. 2004 Aug;54(2):122-6. doi: 10.1007/s00280-004-0786-1. Epub 2004 May 8. — View Citation
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Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Blood and Urine Acetyl-Amantadine levels in patients with GBM | Samples of plasma and urine will be analyzed by established analytical methods (as developed by Biopharmaceutical Research Inc., Vancouver, B.C.; Health Canada and FDA approved). Quantitative analysis of amantadine and acetyl-amantadine in plasma and urine samples will be performed using liquid chromatography triple quadrupole tandem mass spectroscopy (LC-MS/MS). Samples (50 µl) will be spiked with 50 µl of internal standard, deuterated acetyl-amantadine (d3-Ac-amantidine), and proteins precipitated with 0.5 ml of ice-cold methanol. The lyophilized deproteinated samples are reconstituted in 0.1 ml of 0.1% formic acid. Samples are injected onto a C-18 stationary column and eluted using a gradient mobile phase consisting of 0.1% aqueous formic acid (A) and 0.1% formic acid in methanol (B). The run time for each sample is 9 minutes with the mobile phase starting at 5% B and increasing to 95% B during sample elution. | This outcome will be assessed every 8 to 12 weeks. This will continue through study completion, an average of two years. | |
Secondary | GBM tumor volume in correlation with serum and urine acetyl-amantadine levels in patients with GBM | Standard of care MRI will be used. Definitions of response to standard therapy (progression, stable disease, response) will follow the established Response Assessment in Neuro-Oncology (RANO) guidelines9.
Post-hoc volumetric analysis will be done using quantitative semi-automated Olea Sphere software (Olea Medical, France). The study does not require additional MRI scans to be performed; Routine MRI images, as per glioblastoma standard of treatment, are posted to Radiology Information System/Picture Archiving and Communication System (RISPACS) and will be accessed for analysis. |
This outcome will be assessed every 8 to 12 weeks. This will continue through study completion, an average of two years. |
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