Clinical trial · Interventional
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma
NCT04530006CI-TRIAL-00074296unknownN/AClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Glioblastoma Multiforme | Glioblastoma | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Amantadine Hydrochloride | Diagnostic Test | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- GBM Patients
- description
- This cohort of patients will be asked to orally ingest 200mg dose of FDA approved drug amantadine hydrochloride. This will be done at the following timepoints: 1. Within 4 weeks of the start of treatment; but as close to commencement of treatment (Day 1 of radiotherapy) as possible for newly diagnosed patients. 2. Cycle 1, Day 1 of chemotherapy (temozolomide or lomustine) +/- 7 days 3. Day 1 +/- 7 days for each visit where MRI is obtained (typically every 8-12 weeks - pre-cycles 4, 7, 10, for temozolomide or pre-cycles 3, 5, and 7 for lomustine)
- interventionNames
- Diagnostic Test: Amantadine Hydrochloride
Primary outcomes (1)
- measure
- Blood and Urine Acetyl-Amantadine levels in patients with GBM
- timeFrame
- This outcome will be assessed every 8 to 12 weeks. This will continue through study completion, an average of two years.
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (6)
- BACKGROUNDOstrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009-2013. Neuro Oncol. 2016 Oct 1;18(suppl_5):v1-v75. doi: 10.1093/neuonc/now207. No abstract available. PMID 28475809
- BACKGROUNDBabbar N, Hacker A, Huang Y, Casero RA Jr. Tumor necrosis factor alpha induces spermidine/spermine N1-acetyltransferase through nuclear factor kappaB in non-small cell lung cancer cells. J Biol Chem. 2006 Aug 25;281(34):24182-92. doi: 10.1074/jbc.M601871200. Epub 2006 Jun 6. PMID 16757480
- BACKGROUNDGabrielson 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. PMID 15138709
- BACKGROUNDHuang W, Eickhoff JC, Mehraein-Ghomi F, Church DR, Wilding G, Basu HS. Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis. Prostate. 2015 Aug 1;75(11):1150-9. doi: 10.1002/pros.22996. Epub 2015 Apr 20. PMID 25893668
- BACKGROUNDTappia PS, Maksymiuk AW, Sitar DS, Akhtar PS, Khatun N, Parveen R, Ahmed R, Ahmed RB, Cheng B, Huang G, Bach H, Hiebert B, Ramjiawan B. Predictive value and clinical significance of increased SSAT-1 activity in healthy adults. Future Sci OA. 2019 Jul 1;5(7):FSO400. doi: 10.2144/fsoa-2019-0023. PMID 31428447
- BACKGROUNDWen 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.