Metabolic Phenotypes in Melanoma (MetaMel)

Identification of Metabolic Phenotypes Associated With Prognosis and Therapeutic Response in Patients With Melanoma

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.

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.

Blood and tissue samples to be collected for translational research studies, no other additional intervention.

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)

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)

Defined as the time from surgery to disease recurrence or melanoma-related death, whichever occurs first

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