Quantitative Analysis of PET/CT Images of Immune Related Side Effects in Metastatic Melanoma Patients

January 12, 2024 updated by: Institute of Oncology Ljubljana

New cancer treatment with immune-checkpoint inhibitors (ICIs) has changed the way patients with melanoma and a variety of other cancers are being treated. Many pivotal trials that showed efficacy and safety of ICIs were performed in malignant melanoma. ICI can cause a different type of toxicity, called immune-related adverse events (irAEs). Though the exact pathophysiology is not completely understood, it is believed that irAEs are provoked by immune upregulation and inflammation. However, they can be serious, life-threatening, and warrant hospital admission as well. Dangerous irAEs include myocarditis, myositis, and pneumonitis, among others. Due to the novel mechanism of action, unpredictable nature, and wide usage of this type of treatment in the future, there is urgent need for better control of these potentially dangerous side effects. Early recognition and treatment of irAEs are of great importance in successful management.

Positron emission tomography-computed tomography (PET/CT) with [18F]2fluoro-2-deoxy-D-glucose (18F-FDG) is a sensitive, non-invasive, and widely used method for diagnosis and evaluation of treatment efficacy of malignant melanoma. The combination of 18F-FDG-PET and CT allows for assessment of both functional and morphological status of the lesions, and so facilitates better clinical decisions and patient care during treatment. It is also a very sensitive method for recognising inflammation, that can be a signal of irAEs.

Quantitative analysis is a rapidly evolving field of PET/CT image analysis. It includes both radiomics and artificial intelligence. Some studies have reported that quantitative analysis could predict efficacy of different cancer treatments. Quantitative image analysis in cancer response assessment is a rapidly expanding field, with the ultimate goal of clinical translation. However, in the specific instance of irAE diagnosis, it is not yet clear what role quantitative analysis of PET/CT scans can play.

The hypothesis is that quantitative analysis of PET/CT images provides more information on possible irAE, thus helping to treat these side effects more quickly and successfully.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

New cancer treatment with immune-checkpoint inhibitors (ICIs) has changed the way patients with melanoma and a variety of other cancers are being treated. Based on many positive randomised controlled trials in metastatic and neo-/adjuvant setting, ICI agents targeting programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have become invaluable in the treatment of different carcinomas. Many pivotal trials that showed efficacy and safety of ICIs were performed in malignant melanoma.

ICI can cause a different type of toxicity, called immune-related adverse events (irAEs), that can occur in any organ of the body. Though the exact pathophysiology is not completely understood, it is believed that irAEs are provoked by immune upregulation and inflammation. In general, they are less frequent compared to chemotherapy toxicities and usually low grade and manageable. However, they can be serious, life-threatening, and warrant hospital admission as well. Dangerous irAEs include myocarditis, myositis, and pneumonitis, among others. Due to the novel mechanism of action, unpredictable nature, and wide usage of this type of treatment in the future, there is urgent need for better control of these potentially dangerous side effects. Early recognition and treatment of irAEs are of great importance in successful management.

Positron emission tomography-computed tomography (PET/CT) with [18F]2fluoro-2-deoxy-D-glucose (18F-FDG) is a sensitive, non-invasive, and widely used method for diagnosis and evaluation of treatment efficacy of malignant melanoma. The combination of 18F-FDG-PET and CT allows for assessment of both functional and morphological status of the lesions, and so facilitates better clinical decisions and patient care during treatment. It is also a very sensitive method for recognising inflammation, that can be a signal of irAEs.

Quantitative analysis is a rapidly evolving field of PET/CT image analysis. It includes both radiomics and artificial intelligence. Quantitative analyses of medical images provide insight into hidden information about the image, which is usually not fully assessed by a nuclear medicine specialist (for example, information on the spatial heterogeneity of the tumour). Some studies have reported that quantitative analysis could predict efficacy of different cancer treatments. Quantitative image analysis in cancer response assessment is a rapidly expanding field, with the ultimate goal of clinical translation. However, in the specific instance of irAE diagnosis, it is not yet clear what role quantitative analysis of PET/CT scans can play.

The hypothesis is that quantitative analysis of PET/CT images provides more information on possible irAE, thus helping to treat these side effects more quickly and successfully. The association of quantitative PET/CT analysis with patient survival and the predictive value of an early-time point PET/CT scan in response to ICIs will be prospectively examined. The positive impact or irAE of autoimmune thyroiditis on the outcome of ICIs treatment will be also will be also evaluated.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Slovenia
      • Ljubljana, Slovenia
        • Institute of Oncology Ljubljana

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • - Older than 18 years old
  • Cyto- or histologically proven melanoma
  • Stage III.D unresectable/ stage IV melanoma (AJCC classification, 8th edition, 2018)
  • Asymptomatic brain metastases
  • Three measurable metastatic lesions
  • 1st, 2nd, further line of systemic treatment with ICIs (either ipilimumab, nivolumab, pembrolizumab, or combination)
  • PS WHO 0-2 (ECOG criteria)
  • FDG-PET within four weeks of treatment initiation
  • Written consent form

Exclusion Criteria:

  • Symptomatic brain metastases
  • PS WHO > 2 (ECOG criteria)
  • Contraindications for ICI treatment
  • Other malignant diseases (not included: BCC, SCC, in situ carcinoma of cervix, other cured malignant diseases without relapse more than three years)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: This study will prospectively collect data from metastatic or stage III.D unresectable melanoma pts

Timing of PET/CT scans:

  • Baseline PET/CT less than 4 weeks before first ICI infusion
  • Follow-up: 4 weeks (+/- 5 days) after first infusion, 16 weeks (+/- 7 days) after first infusion, then after every 16 weeks (+/- 7 days) or before in case of PD suspicion
Diagnostic test: additional PET/CT at 4 weeks, analysing using quantative analysis
Patient with metastatic melanoma will be monitored with additional PET/CT at 4 weeks, analysing using quantative analysis will be done.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
predictive value of PET/CT for detecting irAE
Time Frame: two years
PET/CT will be performed regularly in metastatic melanoma patients treated with ICIs. Imaging will be analysed for detection of irAE, using in-depth radiological (nuclear) and quantitative (radiomic and artificial intelligence) analysis of affected organs. SUV percentiles of 18F-FDG uptake in the affected organs will be used for prediction of irAE.
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Oncology Ljubljana

Investigators

  • Principal Investigator: Nežka Hribernik, M.D., Institute of Oncology Ljubljana, Slovenia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2020

Primary Completion (Actual)

September 1, 2023

Study Completion (Estimated)

September 10, 2025

Study Registration Dates

First Submitted

December 28, 2023

First Submitted That Met QC Criteria

January 12, 2024

First Posted (Estimated)

January 17, 2024

Study Record Updates

Last Update Posted (Estimated)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KME RS 0120-256/2020-14

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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