Biomarkers in Immunotherapy of Melanoma

May 17, 2023 updated by: Institute of Oncology Ljubljana

Effectiveness of Immunotherapy in the First-line Treatment of Disseminated Melanoma and Recognition of Prognostic and Predictive Biomarkers From the Primary Tumor, Stool and Body Fluids: PROTOCOL TRIAL

Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest biomarkers from the primary tumor, stool and body fluids as markers of response. This prospective study will evaluate gastrointestinal microbiome (bacterial spices and virome) composition and exosomal mRNA expression of PD-L1 and IFNγ correlation with radiological response rates to ICIs treatment of advanced melanoma patients. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to the study. Stool samples are submitted before the start of treatment, at the 12 (+/-2) week and 28 (+/-4) week, and at the event ( such as, suspected disease progression/hyperprogressio, immune related adverse event (irAE), etc). Peripheral venous blood samples are taken additionaly at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether human gastrointestinal microbiome (bacterial and viral) and exosomal mRNA expression of PD-L1 and IFNγ predict response to treatment with PD-1 and CTLA-4 inhibitors and are associated with occurrence of irAE in patients with metastatic melanoma at different time points. Response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclussion: Despite the great success of the treatment of metastatic melanoma with immunotherapy, there remains a significant proportion of patients who do not respond to treatment or who develop severe adverse events during treatment. Identification of novel predictive and prognostic biomarkers for immunotherapy treatment response is therefore necessary. This study is the first to combine and investigate multiple potential predictive and prognostic biomarkers and its dynamics. The results could serve for a better and multi-level understanding of the various factors influencing immunotherapy treatment.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

150

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 Contact

Study Locations

      • Ljubljana, Slovenia
        • Recruiting
        • Institute of Oncology Ljubljana
        • Contact:

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:

  • Age over 18 years
  • Cytologically or histologically verified malignant melanoma
  • Stage IIID unresectable/IV according to AJCC classification (8th edition, 2018)
  • Performance status according to WHO 0 - 2 (ECOG criteria)
  • 1st line of systemic treatment with immunotherapy (nivolumab, ipi/nivo, pembrolizumab)
  • Triple CT/PET CT done within 4 weeks before the first application
  • Signed consent to participate in clinical research

Exclusion Criteria:

  • Previously treated melanoma with systemic therapy
  • Capacity status according to WHO 3 - 4 (ECOG criteria)
  • Contraindications for immunotherapy treatment (known deficiency of the immune system or active immunosuppressive treatment or active autoimmune disease requiring treatment)
  • Other malignant diseases (except cured basal cell carcinoma and squamous cell carcinoma)

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Immune checkpoint inhibitors
Identification of novel predictive and prognostic biomarkers for immunotherapy treatment response in metastatic melanoma

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
response prediction in first line immune checkpoint inhibitors treatment in metastatic melanoma assessed by human gastrointestinal microbiome (bacterial and viral) and exosomal mRNA expression of PD-L1 and IFNγ
Time Frame: 3 years
Primary objectives are to determine whether human gastrointestinal microbiome (bacterial and viral) and exosomal mRNA expression of PD-L1 and IFNγ predicts response to treatment with PD-1 and CTLA-4 inhibitors and are associated with occurrence of irAE in patients with metastatic melanoma.
3 years

Collaborators and Investigators

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

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)

October 5, 2022

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

April 19, 2023

First Submitted That Met QC Criteria

May 17, 2023

First Posted (Actual)

May 30, 2023

Study Record Updates

Last Update Posted (Actual)

May 30, 2023

Last Update Submitted That Met QC Criteria

May 17, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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