Biomarkers in Immunotherapy of Melanoma

Trial Title: Biomarkers in Immunotherapy of Melanoma

NCT ID: NCT05878977

Condition: Metastatic Melanoma
Immune Checkpoints Inhibitors
Gastrointestinal Microbiome (Bacterial and Viral)
Exosomal mRNA Expression of PD-L1 and IFNγ

Conditions: Official terms:
Melanoma
Immune Checkpoint Inhibitors

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Immune checkpoint inhibitor
Description: Identification of novel predictive and prognostic biomarkers for immunotherapy treatment response in metastatic melanoma
Arm group label: Immune checkpoint inhibitors

Summary: 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.

Detailed description: The goal of this [type of study: observational study or clinical trial] is to [learn about, test, compare etc.] in [describe participant population/health conditions]. The main question[s] it aims to answer are: - [question 1] - [question 2] Participants will [describe the main tasks participants will be asked to do, treatments they'll be given and use bullets if it is more than 2 items].

Criteria for eligibility:
Criteria:
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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Institute of Oncology Ljubljana

Address:
City: Ljubljana
Country: Slovenia

Status: Recruiting

Contact:
Last name: Tanja Mesti

Phone: +38615879287
Email: tmesti@onko-i.si

Start date: October 5, 2022

Completion date: December 31, 2027

Lead sponsor:
Agency: Institute of Oncology Ljubljana
Agency class: Other

Collaborator:
Agency: Blood Transfusion Centre of Slovenia
Agency class: Other

Collaborator:
Agency: University Medical Centre Ljubljana
Agency class: Other

Collaborator:
Agency: University of Ljubljana
Agency class: Other

Source: Institute of Oncology Ljubljana

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05878977