Evaluation of Neoadjuvant Electrochemotherapy with Bleomycin versus Electroporation Alone in Colorectal Cancer Patients: A Randomized Controlled Trial

The primary objective of this study is to evaluate the efficacy of **electrochemotherapy** as a treatment modality for tumor downstaging in patients with colorectal cancer, compared to electroporation alone, prior to intended curative surgery. This is clinically relevant as it may enhance the effectiveness of preoperative treatment, potentially improving surgical outcomes and patient prognosis.

Secondary objectives include investigating whether electrochemotherapy induces an immunologic invasion of the primary tumor and whether it elicits a systemic immunologic response. These objectives are important for understanding the broader immunological effects of the treatment, which could inform future therapeutic strategies and improve patient management.

The clinical trial focuses on patients diagnosed with **colorectal cancer**, specifically targeting those with endoscopically suspected or histologically verified malignant tumors of the rectum or sigmoid colon. The study population includes both male and female participants aged 18 years and older, with an ASA classification of I-II, indicating a generally healthy status with mild systemic disease. The trial does not involve a vulnerable population. Participants were selected based on their mental capability to understand the information provided and their ability to give written informed consent. The trial population was reviewed by a multidisciplinary team, ensuring that cases are considered curable with standard surgical resection. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized controlled trial** to evaluate the efficacy of electrochemotherapy in patients with **colorectal cancer**. The trial aims to assess whether the addition of **bleomycin** to electroporation is an effective treatment modality for tumor downstaging prior to curative surgery. The study is conducted in a double-blind manner, ensuring that neither the participants nor the investigators are aware of the treatment assignments, which include either the active treatment with bleomycin or a placebo with saline. The trial is categorized as a Phase 4 study, indicating it is conducted after the treatment has been marketed to gather additional information on the drug's effect in a larger population.

The trial is expected to run from December 2021 to July 2026, with participant involvement lasting approximately one month. The study includes several key visits: an initial screening visit to confirm eligibility, treatment administration visits, and follow-up visits to monitor adverse events and treatment efficacy. The inclusion criteria require participants to be adults aged 18 years or older, with a histologically verified malignant tumor of the rectum or sigmoid colon, and deemed curable with standard surgical resection. Participants must also be mentally capable of understanding the study information and provide written informed consent. Exclusion criteria are not specified in the provided data.

Participants will be monitored for serious adverse events from the time of study treatment until surgery, and any adverse events will be evaluated within 30 days post-treatment. Secondary endpoints include changes in the tumor microenvironment, such as infiltrating lymphocytes and gene and protein expression analysis. The study may terminate early for participants who experience significant adverse events or if the tumor is no longer considered passable at endoscopy. The trial's primary objective is to determine the safety and efficacy of the treatment combination, contributing valuable data to the field of oncology.

The clinical trial involves the administration of **Bleomycin**, marketed as "Bleomycin 'Baxter'", which is provided in the form of a **solution for injection/infusion**. The active substance, **bleomycin**, is a mixture and is classified under the ATC code L01DC01. The pharmaceutical form is a powder that is reconstituted into a solution for intravenous administration. The maximum daily dose is 30,000 IU, with a total maximum dose of 30,000 IU over a treatment period of one day. The administration is conducted intravenously, and the product is not a pediatric formulation. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

The study also includes the use of **saline** as a placebo comparator. The saline solution is also administered intravenously and serves as a control to evaluate the efficacy of the experimental treatment. The maximum daily and total dose of saline is 200 ml, administered over a one-day treatment period. The saline solution is not a pediatric formulation and is used to maintain blinding in the trial. Participant compliance with the administration of the placebo is similarly monitored to ensure the integrity of the study results.

Efficacy in the clinical trial titled "Neoadjuvant electrochemotherapy for colorectal cancer - a randomized controlled trial" will be assessed through both primary and secondary endpoints. The primary endpoints include the evaluation of serious adverse events from the study treatment to surgery and the evaluation of any adverse events reported within 30 days after the study treatment. These assessments will provide insights into the safety and immediate effects of the treatment regimen.

The secondary endpoints focus on changes in the tumor microenvironment. This will involve analyzing infiltrating lymphocytes, bulk and spatial gene and protein expression, and the spatial distribution and organization of bacteria in situ. These parameters will be measured to understand the biological impact of the treatment on the tumor environment, which may correlate with treatment efficacy.

The trial aims to investigate the efficacy of electrochemotherapy as a treatment modality for tumor downstaging compared with electroporation alone, prior to intended curative surgery in patients with colorectal cancer. The study will utilize a randomized controlled trial design to ensure robust and reliable results. The trial is set to conclude by July 1, 2026, with recruitment having started on December 20, 2021.