Ignite Creation Date:
2024-05-06 @ 3:09 PM
Last Modification Date:
2024-10-26 @ 1:43 PM
Study NCT ID:
NCT04530006
Status:
RECRUITING
Last Update Posted:
2024-02-23
First Post:
2020-08-21
Brief Title:
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma
Sponsor:
CancerCare Manitoba
Organization:
CancerCare Manitoba
Study Overview
Official Title:
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed 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 spermidinespermine 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 trials345 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 urine678 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 etal7 reported that human cancer is associated with high urinary concentration of acetyl-amantadine with receiver-operating characteristic ROC for acetyl-amantadine demonstrated to be 0689 CI 0591-0786 95 in lung cancer and 0717 CI 0577-0858 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 radiationchemotherapy will be enrolled in the study An initial assessment of the participants 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
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 spermidinespermine 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 trials345 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 urine678 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 etal7 reported that human cancer is associated with high urinary concentration of acetyl-amantadine with receiver-operating characteristic ROC for acetyl-amantadine demonstrated to be 0689 CI 0591-0786 95 in lung cancer and 0717 CI 0577-0858 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 radiationchemotherapy will be enrolled in the study An initial assessment of the participants 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None