Study Protocol for a Randomized Clinical Trial Investigating the Effect of Reduced Bleomycin in Electrochemotherapy Treatment on Patients with Cutaneous Metastases (The BLESS Trial)

Introduction: Cutaneous metastases in patients with incurable cancer can severely impact quality of life, highlighting the need for minimally invasive treatment options. Electrochemotherapy (ECT) effectively treats tumors across various cancer types by combining a standard chemotherapy dose (15,000 IU/m 2 bleomycin) with electric pulses to enhance drug uptake, aiding in the destruction of the tumor cells. Studies evaluating reduced bleomycin dosage in ECT have shown positive outcomes. This study investigates whether halving the chemotherapy dosage during ECT for cutaneous tumors is as effective as standard ECT treatment. Methods: This double-blinded, randomized clinical trial will include 110 biopsy-verified cutaneous metastases of any cancer type from approximately 55 patients with incurable cancer. Patients will be randomly assigned (1:1 ratio) to receive either a full or half dose of bleomycin. The primary endpoint is overall tumor response after 3 months, assessed using the modified Response Evaluation Criteria in Solid Tumors. Biological samples during ECT will measure the distribution of bleomycin in normal tissue, tumors, and blood via liquid chromatography. In addition, the percentage of tumor cells will be correlated with bleomycin concentration. Side effects will be monitored, and qualitative interviews with a subset of patients before and after treatment will explore their experiences with cutaneous tumors and ECT. The study will be conducted at Zealand University Hospital, Roskilde, and Copenhagen University Hospital, Herlev Gentofte. Discussion: Advances in cancer treatment have led to increased survival rates, and the patients we treat with ECT are often fragile. If the reduced bleomycin dose proves as effective as the standard dosage, it could reduce side effects and thereby benefit elderly, frail, and kidney-compromised patients. The findings of this study may be relevant not only to the treatment of cutaneous metastases but also to deep-seated tumors treated with ECT.