Metabolic Phenotypes in Melanoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Melanoma

Intervention / Treatment
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* Other: [U-13C]Glucose Infusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [U-13C]Glucose Infusion<br>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. | Other: [U-13C]Glucose Infusion<br>* Peri-operative infusion of [U-13C]glucose<br>|
| No Intervention: No [U-13C]Glucose Infusion<br>Blood and tissue samples to be collected for translational research studies, no other additional intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolism