Clinical Trials Logo

Clinical Trial Summary

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.


Clinical Trial Description

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, with a median age of onset of 55 to 60 years. Most patients are treated with postoperative radiation and chemotherapy following their initial surgery. For newly diagnosed, high grade gliomas, the first post-radiation cycle of temozolomide (an oral chemotherapy drug) typically begins four weeks after completion of radiation therapy1. During radiation, temozolomide or lomustine is given daily (seven days per week). Assessment of response and progression is made through brain magnetic resonance imaging (MRI) with contrast, which is typically obtained within one month after completion of radiation therapy and then every two months during adjuvant temozolomide to assess disease status1. With the available standard of care, the median overall survival of patients with glioblastoma remains very low - approximately 10 to 12 months2. The poor prognosis with GBM is a result of an absence of early detection and ineffective treatment options. The proposed exploratory pilot project attempts to addresses the problem of accurate tumor progression monitoring in GBM through the development of a drug biomarker that monitors spermidine/spermine N1-acetyltransferase (SSAT1) activity. SSAT1 is an important enzyme involved in polyamine regulation in the cell. As polyamines are essential for tumor proliferation, SSAT1 is over-expressed in many different cancers, as shown in a number of non-clinical trials3,4,5. These trials provide a rationale for our project: if SSAT1 is overexpressed in cancers including glioblastoma, then a substrate of SSAT1 could serve as a biomarker for determining the cellular activity of SSAT1. An effective substrate is amantadine, and following its acetylation by SSAT1, N-acetyl-amantadine levels excreted in the blood and urine samples of patients with glioblastoma could be used to indicate the presence of upregulation of SSAT1, and therefore, indicative of cancer. Recently published clinical trials involving investigators here at University of Manitoba and CancerCare Manitoba have reported a method for assessing tumor progression in lung and breast cancer patients based on acetyl- amantadine levels in blood and urine6,7,8. The assay is predicated on the selective acetylation of the drug amantadine by SSAT1. Published studies indicate increases in acetyl-amantadine in blood and urine from patients receiving a single oral dose of amantadine was predictive of tumor burden. Tappia et.al.7 reported that human cancer is associated with high urinary concentration of acetyl-amantadine with receiver-operating characteristic (ROC) for acetyl-amantadine demonstrated to be 0.689 (CI: 0.591-0.786, 95%) in lung cancer and 0.717 (CI: 0.577-0.858, 95%) for breast cancer. Given the use of acetyl-amantadine as an early biomarker for lung and breast cancer, the present study protocol examines the extent to which acetyl-amantadine levels in blood and urine can be used to detect glioblastoma progression, particularly tumor recurrence which happens in the majority of patients and is considered inevitable after a median survival time of 32 - 36 weeks1. There are currently no studies that have attempted to determine the diagnostic value of acetyl-amantadine in glioblastoma patients, and therefore, this would be a pilot project. Under this protocol, patients diagnosed with glioblastoma (newly or recurrent) who are following the standard of care (surgical resection and radiation/chemotherapy) will be enrolled in the study. An initial assessment of the participant's baseline acetyl-amantadine levels in blood will be determined at the first visit. Thereafter, participants will be administered a standard 200 mg dose of the Health Canada approved drug amantadine at every visit in which MRI based imaging assessments are being performed (typically, every 8 - 12 weeks). Blood and urine samples will be taken at each visit to assay for acetyl-amantadine levels. These resulting acetyl-amantadine levels will be correlated with MRI based image findings to determine the extent to which this biomarker can be used for treatment monitoring in glioblastoma patients. While the hypothesis is that acetyl-amantadine levels in blood or urine can be used to track tumor progression, an increase in acetyl-amantadine level would not indicate per se what type of tumor was present. For this reason, a metabolic profile on blood and urine samples collected from glioblastoma patients will be performed, to determine if there is a metabolic signature that can be established for glioblastoma. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04530006
Study type Interventional
Source CancerCare Manitoba
Contact Anmol Mann, BSc.
Phone 2049959367
Email manna34@myumanitoba.ca
Status Recruiting
Phase N/A
Start date December 2, 2020
Completion date August 2025

See also
  Status Clinical Trial Phase
Active, not recruiting NCT05023551 - Study of DSP-0390 in Patients With Recurrent High-Grade Glioma Early Phase 1
Recruiting NCT06059690 - Biologic Association Between Metabolic Magnetic Resonance-positron Emission Tomograph (MR-PET) and Tissue Measures of Glycolysis in Brain Tumors of Infiltrating Glioblastoma Cells Phase 1/Phase 2
Recruiting NCT04116411 - A Clinical Trial Evaluating the Efficacy of Valganciclovir in Glioblastoma Patients Phase 2
Terminated NCT01902771 - Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors Phase 1
Recruiting NCT03175224 - APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors Phase 2
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Completed NCT00038493 - Temozolomide and SCH66336 for Recurrent Glioblastoma Multiforme Phase 2
Withdrawn NCT03980249 - Anti-Cancer Effects of Carvedilol With Standard Treatment in Glioblastoma and Response of Peripheral Glioma Circulating Tumor Cells Early Phase 1
Recruiting NCT01923922 - CT Perfusion in the Prognostication of Cerebral High Grade Glioma N/A
Completed NCT01956734 - Virus DNX2401 and Temozolomide in Recurrent Glioblastoma Phase 1
Completed NCT01402063 - PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation Phase 2
Completed NCT01301430 - Parvovirus H-1 (ParvOryx) in Patients With Progressive Primary or Recurrent Glioblastoma Multiforme. Phase 1/Phase 2
Suspended NCT01386710 - Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory GBM And Anaplastic Astrocytoma Phase 1/Phase 2
Active, not recruiting NCT00995007 - A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas Phase 2
Terminated NCT01044966 - A Study of Intraventricular Liposomal Encapsulated Ara-C (DepoCyt) in Patients With Recurrent Glioblastoma Phase 1/Phase 2
Terminated NCT00990496 - A Study Using Allogenic-Cytomegalovirus (CMV) Specific Cells for Glioblastoma Multiforme (GBM) Phase 1
Completed NCT00402116 - Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients Phase 1/Phase 2
Completed NCT00112502 - Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme Phase 2
Completed NCT00504660 - 6-TG, Capecitabine and Celecoxib Plus TMZ or CCNU for Anaplastic Glioma Patients Phase 2
Recruiting NCT05366179 - Autologous CAR-T Cells Targeting B7-H3 in Recurrent or Refractory GBM CAR.B7-H3Tc Phase 1