Electrochemotherapy-Induced Changes in Tumor Microenvironment in Cutaneous Melanoma

Electrochemotherapy Induces Changes in Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma

Cutaneous melanoma frequently develops cutaneous and subcutaneous metastases, which may cause significant morbidity and negatively affect quality of life. Electrochemotherapy (ECT) is an established local treatment modality for cutaneous and subcutaneous tumor lesions that combines the administration of cytotoxic drugs with the application of electric pulses to increase drug uptake into tumor cells.

In addition to its direct cytotoxic effects, electrochemotherapy may induce changes in the tumor microenvironment, including immune cell infiltration, vascular alterations, and other biological responses that could influence tumor control.

The aim of this study is to evaluate changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases following electrochemotherapy with either intravenous bleomycin or intratumoral cisplatin. Tumor tissue samples collected before and after treatment will be analyzed to characterize microenvironmental changes and to compare treated and untreated lesions.

The results of this study may improve understanding of biological effects of electrochemotherapy in melanoma metastases and support further development of treatment strategies.

Study Overview

• Status: Recruiting
• Conditions: MELANOMA; SKIN NEOPLASMS
• Intervention / Treatment: Procedure: Electrochemotherapy

Detailed Description

This is a prospective interventional clinical study designed to investigate electrochemotherapy-induced changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases.

Electrochemotherapy is a local treatment approach that combines electroporation with cytotoxic agents in order to increase intracellular drug delivery and enhance tumor cell death. The treatment is routinely used for superficial tumor lesions, including melanoma metastases, and can be performed using intravenous bleomycin or intratumoral cisplatin.

The primary objective of this study is to characterize changes in the tumor microenvironment in melanoma metastases following electrochemotherapy. Tumor tissue samples will be collected from untreated lesions and from lesions treated with electrochemotherapy. Histopathological and immunohistochemical analyses will be performed to evaluate changes in the tumor microenvironment, including cellular and stromal components, immune-related features, and other relevant biological markers.

The study will include patients with cutaneous melanoma presenting with cutaneous and/or subcutaneous metastases who are eligible for electrochemotherapy as part of their clinical management. Electrochemotherapy will be performed according to established clinical procedures using intravenous bleomycin or intratumoral cisplatin. Biopsy or surgical samples will be collected before and after treatment to enable comparative analyses of treated and untreated tumor tissue.

Collected clinical and pathological data will be used to assess associations between treatment-related microenvironmental changes and patient and lesion characteristics. The study aims to provide additional insight into biological effects of electrochemotherapy beyond local tumor control and may contribute to improved understanding of mechanisms involved in treatment response.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Klavdija Korošec; Phone Number: +386 31630065; Email: kkorosec@onko-i.si
• Study Contact Backup: Name: Neža Gros; Email: ngros@onko-i.si

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • Institute of Oncology Ljubljana
    • Contact: Neža Gros; Email: ngros@onko-i.si
    • Contact: Korošec; Phone Number: +386 31630065; Email: kkorosec@onko-i.si

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18 years or older
• Histologically confirmed cutaneous melanoma
• Presence of cutaneous and/or subcutaneous metastases eligible for electrochemotherapy
• Candidate for electrochemotherapy with intravenous bleomycin or intratumoral cisplatin according to standard clinical practice
• Ability to provide written informed consent

Exclusion Criteria:

• Contraindication to electrochemotherapy or study drugs (bleomycin or cisplatin)
• Pregnancy or breastfeeding
• Severe comorbidities preventing electrochemotherapy
• Inability to comply with study procedures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electrochemotherapy (ECT); Patients with cutaneous melanoma with cutaneous and/or subcutaneous metastases undergoing electrochemotherapy as part of clinical management. Electrochemotherapy is performed using intravenous bleomycin or intratumoral cisplatin. Tumor samples are collected before and after treatment for analysis of tumor microenvironment changes.	Procedure: Electrochemotherapy; Electrochemotherapy is performed according to standard clinical procedures with application of electric pulses combined with administration of cytotoxic agents (intravenous bleomycin or intratumoral cisplatin) for treatment of cutaneous and subcutaneous melanoma metastases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tumor Microenvironment Biomarker Panel After Electrochemotherapy	Change in a predefined panel of tumor microenvironment biomarkers assessed by histopathology and immunohistochemistry in tumor tissue samples collected before and after electrochemotherapy. Biomarkers include immune cell infiltration markers and vascular markers. Results will be reported separately for each biomarker.	Baseline (pre-treatment) and post-treatment (up to 3 months after electrochemotherapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Tumor Microenvironment Biomarkers Between Treated and Untreated Lesions	Comparison of a predefined panel of tumor microenvironment biomarkers (including immune cell infiltration markers and vascular markers) between electrochemotherapy-treated lesions and untreated lesions in the same patient.	Up to 3 months after electrochemotherapy
Local Tumor Control Rate After Electrochemotherapy	Local tumor control of electrochemotherapy-treated cutaneous and subcutaneous melanoma metastases assessed clinically and/or radiologically.	Up to 12 months after electrochemotherapy

Collaborators and Investigators

• Sponsor: Institute of Oncology Ljubljana

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Actual): September 30, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: MELANOMA
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin and Connective Tissue Diseases; Melanoma; Skin Neoplasms; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Drug Therapy; Cytological Techniques; Electrochemical Techniques; Electroporation Therapies; Electroporation; Electrochemotherapy
• Other Study ID Numbers: OI-EKT-MEL-2023; 0120-297/2023/3 (Other Identifier: National Ethics Committee of the Republic of Slovenia)

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