Identification of Metabolic Phenotypes Associated With Prognosis and Therapeutic Response in Patients With Melanoma
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Melanoma
- Sponsor
- Peter MacCallum Cancer Centre, Australia
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- Lactate Utilisation in the TCA cycle
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient has provided written informed consent
- •Male or female aged 18 years or older at written informed consent
- •Presence of a known melanoma lesion requiring surgical excision or biopsy
- •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:
- •Diabetes mellitus
- •Pregnancy or breast feeding
- •Patients unable to comply with study procedures and follow up in the opinion of the investigator
Outcomes
Primary Outcomes
Lactate Utilisation in the TCA cycle
Time Frame: 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)
Glucose Utilisation in the TCA cycle
Time Frame: 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)
Secondary Outcomes
- Relapse free survival(5 years)
- Overall Survival(5 years)