Clinical trial NCT06047015: Irreversible Electroporation (NanoKnife ®) and Immunotherapy for the Treatment of Stage IV Colorectal Cancer
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Liver Metastasis Colon Cancer
Lead sponsor: University of Saskatchewan
Sponsor class: OTHER
First posted: 2023-09-21
Enrollment: 12
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complications
timeFrame: 30 days
measure: Complications
timeFrame: 90 days
measure: Abscopal effect: percent change in non-treated colorectal liver metastasis.
timeFrame: 3 months from the time of IRE
Secondary outcomes:
measure: Tumor-specific immune response: distribution on flow-cytometry plot
timeFrame: Day 8
measure: Tumor-specific immune response: serum cytokine concentrations
timeFrame: Day 8
measure: Tumor-specific immune response: distribution on flow-cytometry plot.
timeFrame: Day 14
measure: Tumor-specific immune response: serum cytokin concentrations
timeFrame: Day 14
measure: Tumor-specific immune response: distribution on flow-cytometry plot.
timeFrame: Day 30
measure: Tumor-specific immune response
timeFrame: Day 30
measure: Progression-free survival
timeFrame: 1 year
measure: Progression-free survival
timeFrame: 2 years
measure: Quality of life questionnaire
timeFrame: baseline
measure: Quality of life questionnaire
timeFrame: 12 weeks
measure: Quality of life questionnaire
timeFrame: 1 year
Other outcomes:
Locations:
Study officials:
References: