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This is a single centre, correlative, longitudinal, biomarker study that aims to describe the metabolic features of human melanoma using mass spectrometry.
This is a single-centre, correlative study designed to investigate metabolic phenotypes in a longitudinal cohort of patients with melanoma. This study will involve the collection of tissue at the time of surgical excision or biopsy. The key intervention, in a subset of patients, will be to perform peri-operative infusions of a stable isotope, [U13C]Glucose. Patients will be intravenously administered sterile, pyrogen-free 13C-glucose, delivered as an 8g bolus followed by infusion of 4g/hour for 2-3 hours. Blood samples will be obtained to monitor glucose and to analyse enrichment of labelled nutrients by gas-chromatography mass spectrometry (GC-MS). At the time of resection or biopsy, tumour samples will be divided and either immediately frozen in liquid nitrogen or processed to form patient-derived xenografts. Frozen tumour samples will be subsequently processed for: isotope enrichment by GC-MS; global metabolomics by liquid-chromatography mass spectrometry (LC-MS); and genomic analyses. Relevant clinical, histologic and genomic features will also be correlated with metabolic findings.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [U-13C]Glucose Infusion | Experimental | A 13.3% solution of sterile, pyrogen-free [U-13C]glucose in sterile water will be infused intravenously rapidly over 10 minutes to a total dose of 8 grams (bolus dose). Then the infusion will change to a rate of 4 grams/ hour. The infusion will continue until the time of tumour excision or biopsy, planned 2-3 hours. |
|
| No [U-13C]Glucose Infusion | No Intervention | Blood and tissue samples to be collected for translational research studies, no other additional intervention. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [U-13C]Glucose Infusion | Other | Peri-operative infusion of [U-13C]glucose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glucose Utilisation in the TCA cycle | In patients receiving a [U-13C]Glucose infusion, assess glucose utilisation in the TCA cycle (using the ratio of citrate M+2/pyruvate M+3, a surrogate of the pyruvate dehydrogenase reaction) | 5 years |
| Lactate Utilisation in the TCA cycle | In patients receiving a [U-13C]Glucose infusion, assess lactate utilisation in the TCA cycle (using the ratio of lactate M+3/3PG M+3 as a surrogate measure) | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse free survival | Defined as the time from surgery to disease recurrence or melanoma-related death, whichever occurs first | 5 years |
| Overall Survival | Measured as the time of surgery until death from any cause |
| Measure | Description | Time Frame |
|---|---|---|
| Tumour Metabolomic and Lipidomic Profiling | Abundance of metabolites and lipid species, quantified by liquid chromatography mass spectrometry | 5 years |
Inclusion Criteria:
Exclusion Criteria:
Patients who meet any of the following criteria will be excluded from receiving a [U-13C]Glucose infusion:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aparna Rao | Contact | +61385595000 | aparna.rao@petermac.org |
| Name | Affiliation | Role |
|---|---|---|
| Aparna Rao, MBBS PhD | Peter MacCallum Cancer Centre, Australia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peter Mac Callum Cancer Centre | Recruiting | Melbourne | Victoria | 3002 | Australia |
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| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| 5 years |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |