Melanoma
Conditions
Keywords
Metabolism
Brief summary
This is a single centre, correlative, longitudinal, biomarker study that aims to describe the metabolic features of human melanoma using mass spectrometry.
Detailed description
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.
Interventions
OTHER[U-13C]Glucose Infusion
Peri-operative infusion of \[U-13C\]glucose
Sponsors
Peter MacCallum Cancer Centre, Australia
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient has provided written informed consent 2. Male or female aged 18 years or older at written informed consent 3. Presence of a known melanoma lesion requiring surgical excision or biopsy 4. Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies and receiving a stable isotope infusion (where applicable)
Exclusion criteria
Patients who meet any of the following criteria will be excluded from receiving a \[U-13C\]Glucose infusion: 1. Diabetes mellitus 2. Pregnancy or breast feeding 3. Patients unable to comply with study procedures and follow up in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Utilisation in the TCA cycle | 5 years | 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) |
| Lactate Utilisation in the TCA cycle | 5 years | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse free survival | 5 years | Defined as the time from surgery to disease recurrence or melanoma-related death, whichever occurs first |
| Overall Survival | 5 years | Measured as the time of surgery until death from any cause |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumour Metabolomic and Lipidomic Profiling | 5 years | Abundance of metabolites and lipid species, quantified by liquid chromatography mass spectrometry |
Countries
Australia
Contacts
Primary ContactAparna Rao
Outcome results
None listed