Liver Metastasis Colon CancerPhase 1/2NCT06047015
Irreversible Electroporation (NanoKnife ®) and Immunotherapy for the Treatment of Stage IV Colorectal Cancer
A Phase 1/2 study testing IRE plus checkpoint inhibitor and IRE plus Checkpoint Inhibitor plus CpG-ODN in people with Liver Metastasis Colon Cancer, run by University of Saskatchewan.
Trial summary
The goal of this pilot clinical trial is to learn about the combination of immune boosting drugs and irreversible electroporation (IRE) in patients with colon cancer that has spread to the liver (metastasis). The main questions it aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Liver Metastasis Colon Cancer
- What is being tested?
- IRE plus checkpoint inhibitor and IRE plus Checkpoint Inhibitor plus CpG-ODN
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- Jul 2025to Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Biopsy-proven colorectal liver metastases with at least one measuring < 3.5 cm in diameter and accessible to percutaneous IRE such that a complete ablation of the lesion is possible.
- Prior resection of the colorectal cancer primary.
- The imaging has been reviewed in multi-disciplinary Rounds and the colorectal liver metastases have been deemed unresectable.
- Patient has undergone chemotherapy and has not converted to resectable disease.
- Radiologic evidence of stable disease for at least two months on systemic therapy for colorectal cancer (may have had prior partial response or disease progression)
- Microsattelite instability (MSI)-stable or mismatch-proficient tumors
- Patient has HLA phenotype of Human Leukocyte Antigen (HLA) A1 or HLA A2.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Size of the metastasis being treated with IRE > 3.2 cm or < 2 cm.
- Size of any non-IRE-treated liver metastasis > 4 cm
- Pregnancy
- Major comorbid disease
- Active autoimmune disease
- Bone or brain or peritoneal metastases.
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- MSI High disease
- Patients with cardiac arrhythmia other than rate controlled atrial fibrillation.
- Metal implant that cannot be removed within 10 cm of the area to be treated.
- Peritoneal disease.
- Poor performance status
- Cirrhosis
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Immune Response to Irreversible Electroporation (NanoKnife ®) and a Checkpoint Inhibitor With or Without CpG Oligodeoxynucleotides for the Treatment of Stage IV Colorectal Cancer
The goal of this pilot clinical trial is to learn about the combination of immune boosting drugs and irreversible electroporation (IRE) in patients with colon cancer that has spread to the liver (metastasis). The main questions it aims to answer are:
- to document the rate of complications associated with combining IRE with immune boosting drugs.
- After one liver metastasis is treated with IRE and immune boosting drugs, what is the change in the size of the non-IRE-treated liver metastases?
- What is the immune response (measured in a blood sample) when IRE is combined with one or two types of immune boosting drugs?
Read the detailed description
Single-centre pilot study of the use of IRE for the treatment of 12 patients with unresectable colorectal liver metastases to assess feasibility and gain preliminary data to inform the design of a larger study.
- Conditions
- Liver Metastasis Colon Cancer
- Being tested
- IRE plus checkpoint inhibitor, IRE plus Checkpoint Inhibitor plus CpG-ODN
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IRE plus checkpoint inhibitorCombination product
Nivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment.
IRE plus Checkpoint Inhibitor plus CpG-ODNCombination product
Patients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug.
IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al.
| Study group | Role | What they receive |
|---|---|---|
| IRE plus Checkpoint Inhibitor | Experimental | Nivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment.
IRE is performed in the CT scanner. Patients will receive a general anesthetic, and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al. Receives: Combination Product: IRE plus checkpoint inhibitor |
| IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN) | Experimental | Patients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG-ODN solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug.
IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al. Receives: Combination Product: IRE plus Checkpoint Inhibitor plus CpG-ODN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complications
Complications (Clavien-Dindo classification of complications) at 30 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.
Measured: 30 days
Complications
Complications (Clavien-Dindo classification of complications) at 90 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.
Measured: 90 days
Abscopal effect: percent change in non-treated colorectal liver metastasis.
Two radiologists (one diagnostic and the other interventional) will examine the scans of all patients. They will select a colorectal metastasis from the scan just before the intervention that is between 2-3.2 cm in maximal diameter, accessible to percutaneous ablation, and treatable according to the interventional radiologist's opinion. Another metastasis, with a maximal diameter of less than 4 cm, will be selected to monitor for the abscopal effect (reduction in size of a colorectal liver metastasis that was not treated with IRE).
After 3 months, the radiologists will review the imaging again. They will assess the treatment mass area for any contrast uptake indicating incomplete ablation. The second metastasis will be measured in the same dimensions as before treatment. The difference in maximal diameter of the second metastasis will be calculated as (diameter before IRE - diameter after IRE) / diameter before IRE and expressed as a percentage.
Measured: 3 months from the time of IRE
Secondary outcomes (11)
Tumor-specific immune response: distribution on flow-cytometry plot
Distribution of Carcinoembryonic (CEA)-specific CD8+ T cells, CD4+ T cells, type-1 and 2 macrophages (M1 and M2), regulatory T (Treg) cells on the flow-cytometry plot.
Measured: Day 8
Tumor-specific immune response: serum cytokine concentrations
Interleukin(IL)-2, Interferon (IFN)-α, IFN-γ, IL-10 and Transforming Growth Factor (TGF)-β.
Measured: Day 8
Tumor-specific immune response: distribution on flow-cytometry plot.
Distribution of Carcinoembryonic (CEA)-specific CD8+ T cells, CD4+ T cells, type-1 and 2 macrophages (M1 and M2), regulatory T (Treg) cells on the flow-cytometry plot.
Measured: Day 14
Tumor-specific immune response: serum cytokin concentrations
Interleukin(IL)-2, Interferon (IFN)-α, IFN-γ, IL-10 and Transforming Growth Factor (TGF)-β.
Measured: Day 14
Tumor-specific immune response: distribution on flow-cytometry plot.
Distribution of Carcinoembryonic (CEA)-specific CD8+ T cells, CD4+ T cells, type-1 and 2
Measured: Day 30
Tumor-specific immune response
Interleukin(IL)-2, Interferon (IFN)-α, IFN-γ, IL-10 and Transforming Growth Factor (TGF)-β.
Measured: Day 30
Progression-free survival
Progression-free survival will be determined based on the CT scan conducted after one year. To prove the absence of progression, there should be no contrast uptake in the area that was treated with IRE one year prior, AND the maximal diameter of the second lesion (not treated with IRE) should have increased by less than 10%.
Measured: 1 year
Progression-free survival
Progression-free survival will be determined based on the CT scan conducted after two years. To prove the absence of progression, there should be no contrast uptake in the area that was treated with IRE two years prior, AND the maximal diameter of the second lesion (not treated with IRE) should have increased by less than 10%
Measured: 2 years
Quality of life questionnaire
Quality of life using FACT-G (Functional Assessment of Cancer Therapy-General) questionnaire, a 27-item questionnaire, each item to be rated 1-5. The scores are totalled and total scores range from 0-108, with higher scores indicating a higher quality of life.
Measured: baseline
Quality of life questionnaire
Quality of life using FACT-G (Functional Assessment of Cancer Therapy-General) questionnaire, a 27-item questionnaire, each item to be rated 1-5. The scores are totalled and total scores range from 0-108, with higher scores indicating a higher quality of life.
Measured: 12 weeks
Quality of life questionnaire
Quality of life using FACT-G (Functional Assessment of Cancer Therapy-General) questionnaire, a 27-item questionnaire, each item to be rated 1-5. The scores are totalled and total scores range from 0-108, with higher scores indicating a higher quality of life.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2023
- Study startJul 2025 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver Metastasis Colon CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This will be a pilot study examining 6 patients treated with IRE and checkpoint inhibitor (first 6, non-randomized) and 6 patients treated with IRE and checkpoint inhibitor and CpG
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Saskatchewan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mike Moser, University of Saskatchewan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06047015
- Sponsor's protocol ID
- IREIMMU
- Status last verified
- Aug 2024
- First submitted
- 21 Feb 2023
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Response to Irreversible Electroporation (NanoKnife ®) and a Checkpoint Inhibitor With or Without CpG Oligodeoxynucleotides for the Treatment of Stage IV Colorectal Cancer
- ClinicalTrials.gov ID
- NCT06047015
- Acronym / sponsor ID
- IREIMMU
- Conditions
- Liver Metastasis Colon Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University of SaskatchewanUniversity, hospital or other
- Study start
- Jul 2025 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 21 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this pilot clinical trial is to learn about the combination of immune boosting drugs and irreversible electroporation (IRE) in patients with colon cancer that has spread to the liver (metastasis). The main questions it aims to answer are:
- to document the rate of complications associated with combining IRE with immune boosting drugs.
- After one liver metastasis is treated with IRE and immune boosting drugs, what is the change in the size of the non-IRE-treated liver metastases?
- What is the immune response (measured in a blood sample) when IRE is combined with one or two types of immune boosting drugs?
Detailed description
Single-centre pilot study of the use of IRE for the treatment of 12 patients with unresectable colorectal liver metastases to assess feasibility and gain preliminary data to inform the design of a larger study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This will be a pilot study examining 6 patients treated with IRE and checkpoint inhibitor (first 6, non-randomized) and 6 patients treated with IRE and checkpoint inhibitor and CpG
| Arm | Type | Receives |
|---|---|---|
| IRE plus Checkpoint Inhibitor | Experimental | Combination Product: IRE plus checkpoint inhibitorNivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment. IRE is performed in the CT scanner. Patients will receive a general anesthetic, and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al. |
| IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN) | Experimental | Combination Product: IRE plus Checkpoint Inhibitor plus CpG-ODNPatients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG-ODN solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug. IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Biopsy-proven colorectal liver metastases with at least one measuring < 3.5 cm in diameter and accessible to percutaneous IRE such that a complete ablation of the lesion is possible.
- Prior resection of the colorectal cancer primary.
- The imaging has been reviewed in multi-disciplinary Rounds and the colorectal liver metastases have been deemed unresectable.
- Patient has undergone chemotherapy and has not converted to resectable disease.
- Radiologic evidence of stable disease for at least two months on systemic therapy for colorectal cancer (may have had prior partial response or disease progression)
Key exclusion criteria (12 listed)
- Size of the metastasis being treated with IRE > 3.2 cm or < 2 cm.
- Size of any non-IRE-treated liver metastasis > 4 cm
- Pregnancy
- Major comorbid disease
- Active autoimmune disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IRE plus checkpoint inhibitorNivolumab: Patients will receive 240 mg nivolumab (dissolved in 250 mL NaCl 0.9%) administered intravenously over 30 minutes. The first dose will take place one or two days before the IRE treatment. The second and third doses will be given 2 and 4 weeks post-IRE. Bloodwork will be done just prior to each treatment. | Combination product | IRE plus Checkpoint Inhibitor |
| IRE plus Checkpoint Inhibitor plus CpG-ODNPatients will receive 240 mg nivolumab as above and also receive 8 mg of CpG-ODN dissolved in 1 mL normal saline administered peritumorally just before the IRE treatment. Three or four electrodes will be placed using a combination of ultrasound and CT guidance in preparation for treatment. Then using the electrodes as landmarks, injection of ¼ or 1/3 cc of the CpG solution will be performed near each of the 3 or 4 electrodes to achieve a peritumoral administration of the drug. IRE is performed in the CT scanner. Patients will receive a general anesthetic and an ultrasound will be performed to locate the designated metastasis. Ultrasound-guided electrode placement (3 or 4 depending on cancer size, shape, and location) will be performed by interventional radiologist Dr. Chris Wall and the IRE device will be activated and used as per the technique of Martin et al. | Combination product | IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN) |
Primary outcome
Complications
Time frame: 30 days
Complications (Clavien-Dindo classification of complications) at 30 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.
Complications
Time frame: 90 days
Complications (Clavien-Dindo classification of complications) at 90 days. The Clavien-Dindo Classification of Complications involves assigning a numbered classification to each complication, from 1-5, with 1 being a complication without need for any intervention required to 5 which is death of the patient. (a higher number indicates a higher severity). This is a validated measure in use for over 25 years.
Abscopal effect: percent change in non-treated colorectal liver metastasis.
Time frame: 3 months from the time of IRE
Two radiologists (one diagnostic and the other interventional) will examine the scans of all patients. They will select a colorectal metastasis from the scan just before the intervention that is between 2-3.2 cm in maximal diameter, accessible to percutaneous ablation, and treatable according to the interventional radiologist's opinion. Another metastasis, with a maximal diameter of less than 4 cm, will be selected to monitor for the abscopal effect (reduction in size of a colorectal liver metastasis that was not treated with IRE). After 3 months, the radiologists will review the imaging again. They will assess the treatment mass area for any contrast uptake indicating incomplete ablation. The second metastasis will be measured in the same dimensions as before treatment. The difference in maximal diameter of the second metastasis will be calculated as (diameter before IRE - diameter after IRE) / diameter before IRE and expressed as a percentage.
11 secondary outcomes
Tumor-specific immune response: distribution on flow-cytometry plot
Time frame: Day 8
Tumor-specific immune response: serum cytokine concentrations
Time frame: Day 8
Tumor-specific immune response: distribution on flow-cytometry plot.
Time frame: Day 14
Tumor-specific immune response: serum cytokin concentrations
Time frame: Day 14
Tumor-specific immune response: distribution on flow-cytometry plot.
Time frame: Day 30
Tumor-specific immune response
Time frame: Day 30
Progression-free survival
Time frame: 1 year
Progression-free survival
Time frame: 2 years
Quality of life questionnaire
Time frame: baseline
Quality of life questionnaire
Time frame: 12 weeks
Quality of life questionnaire
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing IRE plus checkpoint inhibitor and IRE plus Checkpoint Inhibitor plus CpG-ODN in people with Liver Metastasis Colon Cancer, run by University of Saskatchewan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mike AJ Moser, MD, MSc (306-655-5319, mike.moser@usask.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complications (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.