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.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Other: [U-13C]Glucose Infusion

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.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aparna Rao; Phone Number: +61385595000; Email: aparna.rao@petermac.org

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3002
      • Recruiting
      • Peter Mac Callum Cancer Centre
      • Contact: Aparna Rao; Email: aparna.rao@petermac.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour Metabolomic and Lipidomic Profiling	Abundance of metabolites and lipid species, quantified by liquid chromatography mass spectrometry	5 years

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Investigators: Principal Investigator: Aparna Rao, MBBS PhD, Peter MacCallum Cancer Centre, Australia

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2023
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: October 4, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 3, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Metabolism
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: 21/164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No