Irreversible Electroporation (NanoKnife ®) and Immunotherapy for the Treatment of Stage IV Colorectal Cancer

NCT ID: NCT06047015

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-31
• Study Completion Date: 2028-12-31

Brief 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. to document the rate of complications associated with combining IRE with immune boosting drugs.

2. 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?

3. 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.

Conditions

Liver Metastasis Colon Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IRE plus Checkpoint Inhibitor

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.

Group Type: EXPERIMENTAL

IRE plus checkpoint inhibitor

Intervention Type: COMBINATION_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 Oligodeoxynucleotides (CpG-ODN)

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.

Group Type: EXPERIMENTAL

IRE plus Checkpoint Inhibitor plus CpG-ODN

Intervention Type: COMBINATION_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.

Interventions

IRE plus checkpoint inhibitor

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.

Intervention Type: COMBINATION_PRODUCT

IRE plus Checkpoint Inhibitor plus CpG-ODN

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Prior resection of the colorectal cancer primary.

3. The imaging has been reviewed in multi-disciplinary Rounds and the colorectal liver metastases have been deemed unresectable.

4. Patient has undergone chemotherapy and has not converted to resectable disease.

5. 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)

6. Microsattelite instability (MSI)-stable or mismatch-proficient tumors

7. Patient has HLA phenotype of Human Leukocyte Antigen (HLA) A1 or HLA A2.

8. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Size of the metastasis being treated with IRE > 3.2 cm or < 2 cm.

2. Size of any non-IRE-treated liver metastasis > 4 cm

3. Pregnancy

4. Major comorbid disease

5. Active autoimmune disease

6. Bone or brain or peritoneal metastases.

7. MSI High disease

8. Patients with cardiac arrhythmia other than rate controlled atrial fibrillation.

9. Metal implant that cannot be removed within 10 cm of the area to be treated.

10. Peritoneal disease.

11. Poor performance status

12. Cirrhosis

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Saskatchewan

OTHER

Sponsor Role: lead

Responsible Party

Mike Moser

Associate Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Mike AJ Moser, MD, MSc

Role: CONTACT

mike.moser@usask.ca

306-655-5319

Shahid Ahmed, MD

Role: CONTACT

shahid.ahmed@saskcancer.ca

306-655-2630

Other Identifiers

IREIMMU

Identifier Type: -

Identifier Source: org_study_id