Clinical trial
Immune Response to Irreversible Electroporation (NanoKnife ®) and a Checkpoint Inhibitor With or Without CpG Oligodeoxynucleotides for the Treatment of Stage IV Colorectal Cancer
Name
IREIMMU
Description
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?
Trial arms
Trial start
2024-01-01
Estimated PCD
2026-12-01
Trial end
2027-12-01
Status
Not yet recruiting
Phase
Early phase I
Treatment
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.
Arms:
IRE plus Checkpoint Inhibitor
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.
Arms:
IRE plus Checkpoint Inhibitor plus CpG Oligodeoxynucleotides (CpG-ODN)
Size
12
Primary endpoint
Complications
30 days
Complications
90 days
Abscopal effect: percent change in non-treated colorectal liver metastasis.
3 months from the time of IRE
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 12, 'type': 'ESTIMATED'}}
Updated at
2023-09-21
1 organization
2 products
1 indication
Organization
University of SaskatchewanProduct
IREIndication
Liver Metastasis Colon Cancer