Electroporation and Immunotherapy in Metastatic Colorectal Cancer

NCT05609656 | Terminated Phase 2

• 1 other identifier: 2022-500045-25-00
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is designed as an investigator initiated prospective phase 2 study in patients with metastatic pMMR colorectal cancer (CRC) to determine the safety and efficacy of calcium electroporation (CaEP) performed concurrently with irreversible electroporation (IRE) followed by a PD-1 inhibitor (pembrolizumab).

Conditions

Metastatic Colorectal Cancer

Keywords

Irreversible electroporation; Calcium electroporation; Pembrolizumab; Abscopal effect

Outcome Measures

Primary Outcomes (1)

• The incidence rate of adverse events according to CTCAE v. 4.0

  Safety of electroporation and immunotherapy according to CTCAE v. 4.0

  up to 1 month after end of treatment

Secondary Outcomes (4)

• Tumor response by CT

  Baseline compared to 2, 5, 8, 11 months after start of treatment

• Tumor response by ultrasound

  Baseline compared to 2 months after start of treatment

• Progression free survival

  From start of treatment until unequivocal disease progression, assessed up to 5 years

• Overall survival

  From start of treatment until unequivocal disease progression, assessed up to 5 years

Other Outcomes (2)

• immune infiltration by CD3, CD4, and CD8 staining

  Baseline compared to 17 days and 2 months after start of treatment

• immune infiltration by PD-1 and PD-L1 staining

  Baseline compared to 17 days and 2 months after start of treatment

Study Arms (1)

IRE + CaEP + Pembrolizumab

EXPERIMENTAL

Irreversible electroporation (IRE) and calcium electroporation (CaEP) on Day 1, followed by Pembrolizumab on Day 2 (+4 days) and then every 3 weeks (q3w) for up to 12 months in total.

Device: Irreversible electroporation; Device: Calcium electroporation; Drug: Pembrolizumab

Interventions

Irreversible electroporation DEVICE

Percutaneous ablation of a metastatic lesion. Irreversible electroporation is delivered through the NanoKnife system (AngioDynamics, New York, USA). The system is CE approved for medical use.

Also known as: (IRE)

IRE + CaEP + Pembrolizumab

Calcium electroporation DEVICE

Just before the reversible electroporation, calcium chloride will be injected into the primary tumor. The electroporation will be delivered as at least four pulses and up to eight pulses. The device is repositioned after each pulse to ensure coverage of the entire surface area of the tumor. The reversible electroporation regime will be delivered through the endoscopic device EndoVE®, while the ePORE® will be used for pulse generation, both CE approved.

Also known as: (CaEP)

IRE + CaEP + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 200 mg as an IV infusion every 3 weeks (+/- 3 days) for up to 12 months Pembrolizumab is an immune checkpoint inhibitor (PD-1-inhibitor).

Also known as: Keytruda

IRE + CaEP + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Age ≥ 18 years of age
• Histologically confirmed stage IV, non-resectable pMMR colorectal cancer
• The primary malignant tumor is left sided (cancer of the splenic flexure and cancer in regions distal to the splenic flexure, including the rectum)
• The primary tumor is described as reachable at index endoscopy
• At least two metastatic tumors must be present. One metastatic tumor, that in the opinion of the investigators is amenable to IRE, and at least one additional metastatic tumor that will not undergo IRE. Both lesions must be accessible for biopsy
• Previous chemotherapy a), or b):
• Patients refractory to, intolerable of, or refusing standard chemotherapy options including 5-FU, irinotecan, oxaliplatin, bevacizumab and EGFR-inhibitors e.g. panitumumab/cetuximab (if RAS/RAF wild type)
• Patients with favourable biological disease, characterized by
• i. Non-progressive disease ≥ 6 months after last administration of prior 1st line chemotherapy or ≥ 18 months since diagnosis of metastatic disease
• \. Patients in this category must have been exposed to an EGFR-inhibitor if RAS/RAF wild type
• \. Life expectancy greater than 3 months
• \. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• \. Adequate bone marrow function:
• a. Hemoglobin ≥ 5.6 mmol/L or ≥ 9 g/dL, b. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L c. Platelet count ≥ 75 × 109/L

You may not qualify if:

• Prior treatment with an immune checkpoint inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent)
• Concurrent treatment with an investigational medicinal product
• Radiotherapy or major surgery within the last two weeks prior to entering the study
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results E.g
• Uncorrectable coagulation disorder.
• Highly inflamed gastrointestinal tissue which is ulcerated and bleeding
• Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Patients should be excluded if they have an active, known or suspected autoimmune disease (except thyroiditis with replacement therapy and type I diabetes mellitus).
• Patients should be excluded if they have a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies), active chronic, acute hepatitis B (e.g., HBsAg reactive), or hepatitis C (e.g., HCV RNA is detected).
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Allergies and Adverse Drug Reaction:
• i. History of allergy to study drug components ii. History of severe hypersensitivity reaction to any monoclonal antibody
• Patients are excluded if they have active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for \[lowest minimum is four weeks or more\] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least two weeks prior to study drug administration
• Absolute contraindications for IRE:

Sponsors & Collaborators

• Ismail Gögenur: lead

Study Sites (1)

Zealand University Hospital

Køge, 4600, Denmark

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Electroporation; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Study Officials

• Ismail Gögenur

  Zealand University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 8, 2022
• Study Start: January 26, 2023
• Primary Completion: April 8, 2024
• Study Completion: May 2, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)