Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial

Phase 1

• Conditions: Colorectal Cancer
• Interventions: Procedure: Electrochemotheraoy; Procedure: Electroporation with saline (placebo)

• Registration Number: NCT04816045
• Lead Sponsor: Zealand University Hospital

Brief Summary

This is a randomized controlled trial investigating efficacy of electrochemotherapy for early colorectal cancer

Detailed Description

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.

Study Timeline

• Study First Submitted: 2021-02-24
• Status Verified: 2021-03
• Study First Submitted QC: 2021-03-22
• Last Update Submitted: 2021-03-22
• Study First Posted: 2021-03-25
• Last Update Posted: 2021-03-25
• Study Start: 2021-05-01
• Primary Completion: 2023-07-01
• Study Completion: 2023-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Electrochemotheraoy	Electrochemotherapy with bleomycin
Control	Electroporation with saline (placebo)	Electroporation with saline

Primary Outcome Measures

Name	Time	Method
Tumor stage	6 months	Preoperative tumor stage will be compared with pathological assessment of the surgical specimen and comared between the two study arms using TNM stage

Secondary Outcome Measures

Name	Time	Method
Gene expressional changes in the tumor microenvironment	6 months	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.
CD8	6 months	Immunohistochemical staining for CD8
Composition of fusobacterium	6 months	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.
CD3	6 months	Immunohistochemical staining for CD3
VAR2	6 months	Immunohistochemical staining for VAR2
PD-1/PD-L1	6 months	Immunohistochemical staining for PD-1/PD-L1
CD28	6 months	Immunohistochemical staining for CD28