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

Summary

In the last 10 years, the treatment of metastatic cutaneous melanoma has changed dramatically. The new systemic treatment with immunotherapy has led to a dramatic improvement in quality of life and overall survival. Systemic treatment means that the patient receives the drug as an infusion into a vein. Unfortunately, investigators know that immunotherapy is not equally successful in all patients. Recent studies have shown that the success of the treatment is not only influenced by the cellular composition of the metastasis, but also by its surroundings. This is called tumor microenvironment. Depending on the differences in the composition of this microenvironment, some metastases can be described as immunologically hot and others as immunologically cold. Immunologically hot metastases respond better to immunotherapy than immunologically cold metastases.

Studies have shown that with some interventions can change the tumor microenvironment from being immune-cold to being immune-hot. Electrochemotherapy is one of the interventions that might improve the efficacy of immunotherapy in cutaneous melanoma. Electrochemotherapy is an established method for the local treatment of tumors, in which only a certain tumor is treated with special electrodes, to which a weak electric current is applied. Investigators hypothesize that electrochemotherapy stimulates the body's own immune response and enables more effective treatment. Since immunotherapy also stimulates the body's own immune response to cutaneous melanoma cells, the interaction of the two drugs could be even more successful. Recent research results support this assumption.

The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy, based on the histologic analysis of treated and untreated metastases before and after treatment. The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used.

The results will help Investigators better understand the synergistic effects of electrochemotherapy and immunotherapy on cutaneous melanoma metastases. The combination of systemic immunotherapy and electrochemotherapy could become an important treatment method for patients with metastatic melanoma.

Conditions

• Cutaneous Malignant Melanoma

Interventions

PROCEDURE

Electrochemotherapy with Intratumoral Cysplatin

ECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 100 μs, 5 kHz). Triggering of the electrical pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. The type of electrode used will be selected according to the size and location of the tumors.

PROCEDURE

Electrochemotherapy with Intravenous Bleomycin

ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 100 μs, 5 kHz). Triggering of the electrical pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. The type of electrode used will be selected according to the size and location of the tumors.

Sponsors & Collaborators

• Slovenian Research Agency

  collaborator OTHER

• Institute of Oncology Ljubljana

  lead OTHER

Principal Investigators

• Barbara Perić · Dep. of Surgical Oncology, Institute of Oncology Ljubljana

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-10

Primary Completion

2026-09-30

Completion

2026-12-31

Countries

• Slovenia

Study Locations