1295TiP Investigation of calcium electroporation (CaEP) therapy in malignant cutaneous and subcutaneous tumours: A non-randomized phase II clinical trial of a novel palliative therapy

Abstract

Skin metastases can occur from any tumour entity and often cause distress. Surgery or radiation are options, limitations arise from size or location and prior treatments. Electroporation (EP) creates transient pores in cell membranes by short high-voltage pulses allowing diffusion of molecules into the cells. EP with systemic chemotherapy is a standard therapy for cutaneous tumours, causing cell death of tumour cells and skin tissue recovering. Calcium-ions (Ca) are part of various signalling pathways. Intracellular Ca overload induces celldeath through ATP depletion as demonstrated in vitro and vivo, with healthy cells recovering. Intratumoural Ca-injection before EP-treament of affected areas is a new, promising palliative treatment reducing use of chemotherapy and interactions anti-tumour-therapies. The purpose of this trial was to investigate CaEP as therapy for cutaneous and subcutaneous tumours. Approval of German and Danish Drug Oversight Agencies and local Ethics Committees was obtained prior to the start of the trial. It was supported from the European Fund for Regional Development as part of the “Changing Cancer Care”-project. This multi-centre non-randomized single-arm phase II trial investigates the use of CaEP in cutaneous and subcutaneous tumours of any cancer histology. All included patients receive CaEP. Primary endpoint is clinical response rate at two months. Response rate is defined as number of responding to treated lesions, evaluated by reduction in size, documented with clinical photography. Secondary endpoints include: treatment response at time points month 1, 3, 4, 6 and 12; histological tissue changes in biopsies one year after treatment; response on MRI on a subset of patients; quality-of-life assessments before treatment, after 2 and 12 months using the EORTC QLQ-C15-PAL questionnaire; examining systemic immune response through routine scans; response due to tumour histology; response rate of all tumours treated; response rate per patient; current of applied pulses and qualitative interviews of one subset of patients. The study is conducted at three cancer centres in Germany and Denmark. EudraCT 2019-004314-34; NCT04225767. The authors.