Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Disease Attributes

Hematinics

All Drugs and Chemicals

Liver Extracts

Patients receiving a liver transplantation that do NOT develop HCC recurrence after liver transplantation.

Patients receiving a liver transplantation that develop HCC recurrence after liver transplantation.

Determination of serum glycomics pre-transplant using an optimal cutoff based on statistic modeling

HCCRecurrencePrognosticScore

Determination of serum glycomics post-transplant using an optimal cutoff based on statistic modeling

HCCRecurrenceDiagnosticScore

Xavier Verhelst, MD, PhD

Emma Butaye

Liver transplantation (LT) is the only curative option for a selection of patients with hepatocellular carcinoma (HCC) based on clinical selection criteria known as the Milan criteria. Nevertheless, 15% of these patients still show tumour recurrence after LT. In a monocentric pilot study, we have demonstrated that specific changes in N-glycan profiles (measured before LT) occur in HCC patients receiving LT1. These specific changes proved to be strongly associated with the risk of HCC recurrence and overall death after LT, independent of the criteria used for stringent patient selection. Pathophysiologically, it is known that abberations in protein glycosylation are involved in the onset en development of HCC. As such, a prognostic biomarker was developed that can clearly differentiate between patients with and without increased risk of HCC recurrence.

The primary goal of this research study is to set up a prospective, multicentre study in order to validate the prognostic value of this glycomics-based serum biomarker. As such, the risk of tumour recurrence in patients undergoing LT for HCC will be estimated independent from the Milan criteria and the French alpha-fetoprotein model as the current standard. The secondary goal is to explore the potential of serum glycomics as markers of early recurrence after LT for HCC. More specifically, we aim to investigate whether serial glycomics determination at fixed time points after LT could allow early detection of recurrent HCC even before it is visible on conventional imaging. Consequently, a diagnostic biomarker for monitoring early recurrence after LT could be developed with the potential of redirecting treatment strategies already in an early disease stage.

In case the promising data from the pilot study will be confirmed, the prognostic biomarker could be implemented in daily clinical practice leading to optimization of patient selection using a simple blood test before LT. More specifically, this marker could improve organ allocation thus preventing unnessecary treatment toxicity for the patient and reducing the costs of treatment for society. Moreover, it should be emphasized that a patent application was already submitted and accepted in collaboration with TechTranfer of Ghent University (PCT/EP2021/057788-Prognostic markers of disease recurrence in liver transplant recipients with hepatocellular carcinoma).

Serum Glycomics as Prognostic and Diagnostic Biomarkers of Disease Recurrence in Liver Transplant Recipients With Hepatocellular Carcinoma

University Hospital, Antwerp

Universitaire Ziekenhuizen KU Leuven

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

University Hospital, Ghent

Nervous System Diseases

Rare Diseases

Glioblastoma

Brain Neoplasms

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Anti-Infective Agents

Analgesics

Anti-Dyskinesia Agents

Cardiotonic Agents

Temozolomide

Lomustine

Amantadine

Antiparkinson Agents

Antiviral Agents

Dopamine

Dopamine Agents

Neurotransmitter Agents

Analgesics, Non-Narcotic

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)

Patients who are eligible for the study will be administered a regular 200 mg dose of FDA approved drug amantadine. 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)

Amantadine Hydrochloride

Anmol Mann, BSc.

Gary Annable

Marshall Pitz, MD, FRCPC

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.

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.

All patients eligible for the study who have provided consent will be asked to ingest a regular 200mg dose of FDA approved drug Amantadine, according to timelines proposed in the protocol.

Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma

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.

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.

University of Manitoba

The Metabolomics Innovation Centre

BioMark Diagnostics Inc.

Canadian Institutes of Health Research (CIHR)

CancerCare Manitoba

Sarcoma

Neoplasms, Connective and Soft Tissue

Soft Tissue Sarcoma

Uterine Sarcoma

Participants were enrolled for the first treatment of uterine sarcoma or secondary operation for recurrence fo uterine sarcoma.

Participants were enrolled for surgery of uterine fibroids.

Diagnostic biomarker

Yan Li, Dr

The purpose of this project was to use multi-omics technology to screen the key factors for the occurrence and development of uterine sarcoma.

Uterine sarcomas are rare mesenchymal neoplasms in the female genital system, accounting for about 1% of female reproductive tract malignancies and 3%\~7% of uterine malignancies. Subtypes of uterine sarcoma are leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. Uterine leiomyosarcoma is the most common uterine sarcoma, accounting for about 1% to 2% of all uterine malignancies.

Uterine sarcomas differ in histologic appearance and clinical behavior. The incidence of uterine sarcoma is low and the prognosis is poor. Its manifestations mainly include abnormal vaginal bleeding, abdominal pain and abdominal mass, but none of these symptoms are specific.

For uterine sarcoma, there are no diagnostic serum markers and imaging features and the diagnosis of uterine sarcoma still mainly depends on postoperative pathological results. However, with the development of omics technology, immunophenotypes and molecular characterization of uterine sarcomas have increasingly been utilized to improve diagnostic classification and prognostication in uterine sarcomas. Uterine leiomyosarcoma, the most common subtype of uterine sarcoma, does not have a single defining molecular abnormality.

This project intends to use multi-omics technology to screen the key factors for the occurrence, development, and malignant transformation of uterine sarcoma, especially uterine leiomyosarcoma, and to map the interaction network of cell signaling pathways. It provides key molecular markers for the early assessment of recurrence and malignant transformation of uterine myoma after conservative treatment, and provides a molecular mechanism basis for finding solutions to prevent the progression and malignant transformation.

Molecular Mechanism Study of Uterine Sarcoma

Analyze genetic susceptibility among women exhibiting disease manifestations of uterine sarcoma

Shixuan Wang

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Serum Glycomics as Prognostic and Diagnostic Biomarkers of Disease Recurrence in Liver Transplant Recipients With Hepatocellular Carcinoma	NCT05866783	Prognostic Biom... Liver Transplan... Diagnostic Biom... Hepatocellular ...	HCCRecurrencePr... HCCRecurrenceDi...	18 Years -	University Hospital, Ghent
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma	NCT04530006	Glioblastoma Mu...	Amantadine Hydr...	18 Years -	CancerCare Manitoba
Serum Glycomics as Prognostic and Diagnostic Biomarkers of Disease Recurrence in Liver Transplant Recipients With Hepatocellular Carcinoma	NCT05866783	Prognostic Biom... Liver Transplan... Diagnostic Biom... Hepatocellular ...	HCCRecurrencePr... HCCRecurrenceDi...	18 Years -	University Hospital, Ghent
Acetyl-Amantadine as a Biomarker in Patients With Glioblastoma	NCT04530006	Glioblastoma Mu...	Amantadine Hydr...	18 Years -	CancerCare Manitoba
Molecular Mechanism Study of Uterine Sarcoma	NCT05881967	Uterine Sarcoma	Diagnostic biom...	18 Years - 99 Years	Tongji Hospital
Molecular Mechanism Study of Uterine Sarcoma	NCT05881967	Uterine Sarcoma	Diagnostic biom...	18 Years - 99 Years	Tongji Hospital
Molecular Mechanism Study of Uterine Sarcoma	NCT05881967	Uterine Sarcoma	Diagnostic biom...	18 Years - 99 Years	Tongji Hospital

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