Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial

Study Overview
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Brief Summary
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This is a randomized controlled trial investigating efficacy of electrochemotherapy for early colorectal cancer

Detailed Description
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This is a phase 2 randomized controlled trial. The study is blinded. The aim of this study is to establish the safety and efficacy of treating patients with early colorectal cancer with electrochemotherapy, compared with electroporation alone, as a down staging and immune-response enhancing treatment prior to intended curative surgery. The study involves recruitment of patients with histologically verified rectal and sigmoid colon cancer with no indication for neoadjuvant chemoradiotherapy (experimental or standard care based) prior to intended curative surgery. In total the study will involve 24 patients, of these, 12 patients are treated with electrochemotherapy (bleomycin) and 12 patients with electroporation alone (placebo) In relation to the intervention, clinical examination, blood samples, biopsies and questionnaires will be collected to evaluate safety, tumor respons and immunologic response to the treatment. Patients will be followed for one month after the elective surgery.

Official Title
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Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Procedure: Electrochemotheraoy
* Procedure: Electroporation with saline (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be mentally capable of understanding the information given. Patients must give written informed consent. Endoscopically suspected or histologically verified malignant tumor of the rectum or sigmoid colon. Tumor described as passable at index endoscopy. Men or women aged at least 18 years. Case reviewed by MDT (surgery, radiology, oncology). Case considered curable with standard surgical resection. ASA class I-II (Classification of the American Society of Anesthesiology) Exclusion Criteria: Indication for neoadjuvant chemoradiation or chemotherapy prior to surgery Uncorrectable coagulation disorder. Patients with ICD or pacemaker units. Ongoing immunosuppressive treatment. Patients with concomitant use of phenytoin. Myocardial insufficiency, defined as NYHA class >2 Concurrent treatment with an investigational medicinal product. Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study recruitments. Advanced tumor stages, clinical UICC stage IV. Acute surgical resection. Pregnancy Medical history of severe pulmonary disease. Previous cumulative dose of bleomycin exceeding 250mg/m2. BMI > 35 Renal impairment, defined as eGFR <40 ml/min

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Electrochemotherapy with bleomycin | Procedure: Electrochemotheraoy<br>* Electrochemotherapy (ECT) is endoscopic electroporation in combination with bleomycin<br>|
| Active Comparator: Control<br>Electroporation with saline | Procedure: Electroporation with saline (placebo)<br>* Electroporation in the control group is performed endoscopically with saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor stage | Preoperative tumor stage will be compared with pathological assessment of the surgical specimen and comared between the two study arms using TNM stage | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expressional changes in the tumor microenvironment | Biopises are collected before the intervention and compared with the surgical specimen using NanoString technology. The PanCancer IO 360 gene panel will be used, a predefined panel of 770 genes. | 6 months | 
| Composition of fusobacterium | To characterize the spatial distribution and organization of bacteria in situ, some of the samples will be assessed microscopically. Confocal laser scanning microscopy will be performed on formalin-fixed, paraffin-embedded tissue of both diseased and normal tissue. This will allow us to investigate treatment affects the bacterial composition of fusobacterium. | 6 months | 
| PD-1/PD-L1 | Immunohistochemical staining for PD-1/PD-L1 | 6 months | 
| CD3 | Immunohistochemical staining for CD3 | 6 months | 
| CD8 | Immunohistochemical staining for CD8 | 6 months | 
| CD28 | Immunohistochemical staining for CD28 | 6 months | 
| VAR2 | Immunohistochemical staining for VAR2 | 6 months |