Back to resultsNeoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial
Primary Purpose
Colorectal Cancer
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Electrochemotheraoy
Electroporation with saline (placebo)
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Intervention
Control
Arm Description
Electrochemotherapy with bleomycin
Electroporation with saline
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
PD-1/PD-L1
Immunohistochemical staining for PD-1/PD-L1
CD3
Immunohistochemical staining for CD3
CD8
Immunohistochemical staining for CD8
CD28
Immunohistochemical staining for CD28
VAR2
Immunohistochemical staining for VAR2
Full Information
NCT ID
NCT04816045
First Posted
February 24, 2021
Last Updated
March 22, 2021
Sponsor
Zealand University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04816045
Brief Title
Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial
Official Title
Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 1, 2021 (Anticipated)
Primary Completion Date
July 1, 2023 (Anticipated)
Study Completion Date
December 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zealand University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Patients and investigators are blinded. The allocation list is located at the pharmacy.
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
Electrochemotherapy with bleomycin
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Electroporation with saline
Intervention Type
Procedure
Intervention Name(s)
Electrochemotheraoy
Intervention Description
Electrochemotherapy (ECT) is endoscopic electroporation in combination with bleomycin
Intervention Type
Procedure
Intervention Name(s)
Electroporation with saline (placebo)
Intervention Description
Electroporation in the control group is performed endoscopically with saline
Primary Outcome Measure Information:
Title
Tumor stage
Description
Preoperative tumor stage will be compared with pathological assessment of the surgical specimen and comared between the two study arms using TNM stage
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Gene expressional changes in the tumor microenvironment
Description
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.
Time Frame
6 months
Title
Composition of fusobacterium
Description
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.
Time Frame
6 months
Title
PD-1/PD-L1
Description
Immunohistochemical staining for PD-1/PD-L1
Time Frame
6 months
Title
CD3
Description
Immunohistochemical staining for CD3
Time Frame
6 months
Title
CD8
Description
Immunohistochemical staining for CD8
Time Frame
6 months
Title
CD28
Description
Immunohistochemical staining for CD28
Time Frame
6 months
Title
VAR2
Description
Immunohistochemical staining for VAR2
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Malene Broholm, MD
Phone
+45 56531500
Email
malea@regionsjaelland.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ismail Gögenur, DMSc
Organizational Affiliation
Zealand University Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Neoadjuvant Electrochemotherapy for Colorectal Cancer - a Randomized Controlled Trial
We'll reach out to this number within 24 hrs