Evaluation of Calcium Chloride Dihydrate Electroporation, Bleomycin Electrochemotherapy, and Irreversible Electroporation in Unresectable Pancreatic Cancer

The primary objective of this study is to evaluate the **efficacy** and safety of irreversible electroporation (IRE), calcium (CaCl2) electroporation, and electrochemotherapy (ECT) in patients with unresectable pancreatic cancer. This is clinically relevant as these interventions may offer alternative therapeutic options for patients with limited surgical possibilities, potentially improving treatment outcomes and quality of life.

Secondary objectives include:

• Evaluating overall survival, reduction in body weight loss, decrease in pain levels, and improvement in quality of life.
• Exploratory objectives such as biomarker analysis (Ca 19-9), morphology and biochemistry analysis (including albumin, protein, lipase, amylase levels, CRP, procalcitonin), and assessing the inflammatory response in IRE, ECT, and CaEP (calcium electroporation).

The clinical trial focuses on patients diagnosed with **unresectable pancreatic cancer**. The study population includes both male and female participants aged over 18 years, with an **ECOG performance status** of 0, 1, or 2, indicating varying levels of general health status. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on specific criteria, including a histopathological confirmation of adenocarcinoma of the pancreas, with lesions defined as unresectable due to specific vascular infiltrations or thrombosis, or those with local recurrence post-resection. Tumor size must not exceed 6 cm on recent imaging, and participants may be undergoing chemotherapy or have a new diagnosis of pancreatic cancer. The trial includes a vulnerable population, emphasizing the need for careful ethical considerations. Lifestyle factors such as diet and physical activity are not detailed in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **irreversible electroporation** (IRE), calcium electroporation, and electrochemotherapy (ECT) in patients with unresectable pancreatic cancer. This study is structured as a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to run until June 30, 2027, with recruitment having commenced on February 10, 2022.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age over 18, histopathological confirmation of adenocarcinoma of the pancreas, and a tumor size not exceeding 6 cm. The inclusion visit will also involve obtaining written informed consent. Follow-up visits will be scheduled to monitor progression-free survival, overall survival, body weight changes, pain levels, and quality of life using standardized scales such as the EORTC QLQ-PAN26 and WHOQOL-BREF. Biomarker levels and changes in morphology and biochemistry panels will also be assessed at predefined time points. The end-of-study visit will conclude the participant's involvement, summarizing the outcomes and any adverse events experienced.

The expected length of participant involvement is contingent upon the progression of the disease or the occurrence of any adverse events that may necessitate early termination from the study. Conditions that could lead to early withdrawal include significant disease progression or severe adverse reactions to the treatment. The primary endpoint of the study is progression-free survival, defined as the time from the initiation of study treatment to the first occurrence of disease progression or death from any cause. Secondary endpoints include overall survival, body weight change, pain level, and quality of life assessments.

The clinical trial involves the administration of **calcium chloride dihydrate** as an experimental medication. The pharmaceutical form of this medication is a **solution for injection**, specifically marketed under the name "CALCIUM CHLORATUM WZF, 67 mg/ml." The solution is administered via **intratumoral use**. The maximum daily dose is 1 g/m³, with a total dose not exceeding 1 g/m³ over the treatment period. The treatment duration is limited to one day. The medication is produced by ZAKLADY FARMACEUTYCZNE POLPHARMA S.A. and is classified under the ATC code A12AA07, indicating its role as a calcium supplement.

Another experimental medication used in the trial is **bleomycin**, marketed as "Bleomedac 15000 IU." This medication is provided in the form of a powder for the preparation of a **solution for injection**. The administration route is by **injection**, with a maximum daily and total dose of 15000 IU. The treatment period is also restricted to one day. Bleomycin is produced by MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL) and is classified under the ATC code L01DC01, indicating its use as a cytostatic agent.

Both medications are utilized in the context of evaluating the efficacy and safety of irreversible electroporation (IRE), calcium electroporation, and electrochemotherapy (ECT) in patients with pancreatic cancer. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the time from the initiation of study treatment to the first occurrence of disease progression or death from any cause. Secondary endpoints include overall survival (OS), which measures the proportion of patients remaining alive from the initiation of study treatment until the last follow-up visit, body weight change at predefined timepoints, pain level assessed using the Visual Analogue Scale (VAS), and quality of life evaluated through EORTC QLQ-PAN26 and WHOQOL-BREF questionnaires.

Exploratory endpoints will also be considered, such as levels of biomarkers like Ca 19-9 measured at 1, 4, and 6 days post-surgery and during standard follow-up visits. Changes in morphology and biochemistry panels, including albumin, protein, lipase, amylase levels, CRP, and procalcitonin, will be monitored according to the schedule of assessments. These parameters will be collected and analyzed at specified timepoints to provide comprehensive data on the efficacy of the treatments being evaluated in patients with pancreatic cancer.