Confirmatory Trial in the Evaluation of Ca Electroporation for the Treatment of Cutaneous Metastases

Summary

Electroporation is a method that can facilitate transport of molecules across the cell membrane and into the cell by means of electrical pulses. The method can be used with molecules that normally have difficulty passing the cell membrane such as chemotherapy (electrochemotherapy). Electrochemotherapy (ECT) is used in cancer therapy, where chemotherapy is administered intratumoral or intravenous, then followed by electrical pulses applied directly on the tumor. The chemotherapy accumulates in the cancer cells which results in an increased cytotoxic effect. The most used chemotherapeutic drug used in electrochemotherapy is bleomycin. Electrochemotherapy is a well-documented local treatment form for especially cutaneous tumors. Today, the treatment is used mostly in palliative care in more than 140 centres around Europe.

In vitro and in vivo studies have shown that the combination of calcium and electroporation is an effective method in killing cancer cells without serious side effects.This new combination opens the possibility of replacing bleomycin with calcium in treatments with electroporation.

Calcium electroporation is a local treatment where calcium is administered intratumoral and followed by electrical pulses applied on the tumor.

The preclinical studies have shown that there is a difference in sensitivity in tumor cells and normal cells, as normal cells tolerate the treatment better than tumor cells (own data manuscript in preparation). The studies have also shown that there is no cell injury by calcium injection without electroporation, the investigators therefore expect that the treatment only will cause minor side effects.

Calcium electroporation would be possible to use on patients for whom chemotherapy is contradicted e.g. severe lung functions impairment, pregnant woman etc. Calcium electroporation is a simple and unexpensive cancer treatment that does not involve any administration of cytotoxic chemotherapy, and can be performed by surgeons, radiologists as well as oncologists. Both electroporation equipment and calcium are already being used in the clinic, so the treatment can easily be implemented.

Conditions

• Cutaneous Melanoma

Interventions

PROCEDURE

Calcium Electroporation

If the patient agrees biopsies will be performed from the tumor area before and after electroporation during local anaesthesia. Maximum of 8 biopsies will be done, depending on the patient's number of metastases. All patient's regardless of the number of metastases will have one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180. Patients with more than 6 metastases: One to two biopsies before treatment, one to two biopsies one week after treatment from metastases treated with calcium and bleomycin respectively. All biopsies will be handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.

PROCEDURE

Bleomycin based electrochemotherapy

If the patient agrees biopsies will be performed from the tumor area before and after electroporation during local anaesthesia. Maximum of 8 biopsies will be done, depending on the patient's number of metastases. All patient's regardless of the number of metastases will have one biopsy from area treated with calcium and one from area treated with bleomycin, after the randomization code is revealed at day 180. Patients with more than 6 metastases: One to two biopsies before treatment, one to two biopsies one week after treatment from metastases treated with calcium and bleomycin respectively. All biopsies will be handled according to current guidelines and analyzed by a pathologist for amount of tumor tissue, inflammation, fibrosis and necrosis.

Sponsors & Collaborators

• Szeged University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-09-20

Primary Completion

2019-06-04

Completion

2019-06-04