- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05609656
Electroporation and Immunotherapy in Metastatic Colorectal Cancer (ELI)
Calcium Electroporation in Combination With Irreversible Electroporation and Immunotherapy in Patients With Proficient Mismatch Repair System (pMMR) Metastatic Colorectal Cancer - A Prospective, Phase 2 Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Tobias F Justesen, MD
- Phone Number: 30239295
- Email: toju@regionsjaelland.dk
Study Contact Backup
- Name: Ismail Gögenur, Professor
- Email: igo@regionsjaelland.dk
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
1. Patients in this category must have been exposed to an EGFR-inhibitor if RAS/RAF wild type
8. Life expectancy greater than 3 months
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
10. 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
11. Adequate kidney function:
a. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or creatinine ≤1.5 X upper limit of normal (ULN)
12. Adequate liver function:
a. Total bilirubin ≤ 1.5 × ULN b. Alanine aminotransferase (ALT): ≤2.5 X ULN or ≤5 X ULN for subjects with liver metastases c. Aspartate aminotransferase (AST): ≤2.5 X ULN or ≤5 X ULN for subjects with liver metastases d. Albumin: >25 g/L
13. Adequate coagulation function:
a. International Normalized Ratio (INR) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as prothrombin Time (PT) or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants b. Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
14. Follow the conditions regarding fertility, pregnancy, or lactation:
- Female and male participants of reproductive potential (for definition refer to appendix 16.1) must agree to avoid becoming pregnant or impregnating a partner, respectively, while receiving pembrolizumab and for 120 days after the last dose
- Participants of reproductive potential must use (or have their partner use) an acceptable method of contraception, as outlined in appendix 16.1, during heterosexual activity, while receiving pembrolizumab and for 120 days after the last dose
- Women of reproductive potential (WORP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to receiving the first dose of pembrolizumab.
- Women must not be breastfeeding.
Exclusion Criteria:
- 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:
- Implanted pacemaker or ICD unit.
- History of epilepsy
- History of cardiac (ventricular) arrhythmia
- Recent myocardial infarction
- Congestive heart failure (>NYHA class 2)
- Uncontrollable hypertension
Relative contraindications for IRE:
- Atrial fibrillation
- Combined severe stenosis of the common hepatic artery and main portal vein branch
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: IRE + CaEP + Pembrolizumab
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.
|
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.
Other Names:
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.
Other Names:
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).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence rate of adverse events according to CTCAE v. 4.0
Time Frame: up to 1 month after end of treatment
|
Safety of electroporation and immunotherapy according to CTCAE v. 4.0
|
up to 1 month after end of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response by CT
Time Frame: Baseline compared to 2, 5, 8, 11 months after start of treatment
|
Based on CT chest/abdomen scans according to RECIST version 1.1
|
Baseline compared to 2, 5, 8, 11 months after start of treatment
|
Tumor response by ultrasound
Time Frame: Baseline compared to 2 months after start of treatment
|
Based on contrast enhanced ultrasound (CEUS) utilizing the standardized and quantitative method Dynamic CEUS (DCEUS)
|
Baseline compared to 2 months after start of treatment
|
Progression free survival
Time Frame: From start of treatment until unequivocal disease progression, assessed up to 5 years
|
From start of treatment until unequivocal disease progression, assessed up to 5 years
|
|
Overall survival
Time Frame: From start of treatment until unequivocal disease progression, assessed up to 5 years
|
From start of treatment until unequivocal disease progression, assessed up to 5 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
immune infiltration by CD3, CD4, and CD8 staining
Time Frame: Baseline compared to 17 days and 2 months after start of treatment
|
immune-related treatment-induced changes
|
Baseline compared to 17 days and 2 months after start of treatment
|
immune infiltration by PD-1 and PD-L1 staining
Time Frame: Baseline compared to 17 days and 2 months after start of treatment
|
immune-related treatment-induced changes
|
Baseline compared to 17 days and 2 months after start of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ismail Gögenur, Zealand University Hospital
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Calcium-Regulating Hormones and Agents
- Pembrolizumab
- Calcium
Other Study ID Numbers
- 2022-500045-25-00
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Colorectal Cancer
-
Mayo ClinicCompletedMetastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Colorectal Carcinoma | Metastatic Rectal Adenocarcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Metastatic... and other conditionsUnited States
-
Emory UniversityBristol-Myers Squibb; National Cancer Institute (NCI); National Institutes of...Active, not recruitingColorectal Cancer Metastatic | Colorectal Adenocarcinoma | Stage IV Colorectal Cancer | Stage IVA Colorectal Cancer | Stage IVB Colorectal Cancer | Refractory Colorectal Carcinoma | Metastatic Microsatellite Stable Colorectal Carcinoma | Stage IVC Colorectal CancerUnited States
-
Array Biopharma, now a wholly owned subsidiary...CompletedMetastatic Colorectal Cancer | Advanced Solid Tumors | Advanced or Metastatic Biliary CancerUnited States
-
Hutchison Medipharma LimitedActive, not recruitingMetastatic Colorectal Cancer | Metastatic Colon CancerUnited States, Spain, Japan, Australia, Austria, Belgium, Czechia, Estonia, France, Germany, Hungary, Italy, Poland, United Kingdom
-
Zhejiang Cancer HospitalNot yet recruitingMetastatic Colorectal Cancer | Metastatic Colorectal Adenocarcinoma | CRCChina
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingMetastatic Pancreatic Adenocarcinoma | Stage IV Pancreatic Cancer AJCC v6 and v7 | Stage IV Colorectal Cancer AJCC v7 | Stage IVA Colorectal Cancer AJCC v7 | Stage IVB Colorectal Cancer AJCC v7 | Metastatic Gastroesophageal Junction Adenocarcinoma | Metastatic Colorectal Carcinoma | Metastatic Malignant... and other conditionsUnited States
-
Dana-Farber Cancer InstituteAmerican Cancer Society, Inc.Not yet recruitingMetastatic Colorectal Cancer | Colorectal Cancer | Metastatic Colon CancerUnited States
-
AmgenCompletedCancer | Metastatic Colorectal Cancer | Colorectal Cancer | Rectal Cancer | Metastatic Cancer | Colon Cancer
-
AmgenCompletedCancer | Metastatic Colorectal Cancer | Colorectal Cancer | Rectal Cancer | Metastatic Cancer | Colon Cancer | Oncology
-
Symphogen A/STerminatedCarcinoma | Metastatic Colorectal Cancer | Colorectal Cancer MetastaticUnited States, Spain, Germany, Italy
Clinical Trials on Irreversible electroporation
-
Fuda Cancer Hospital, GuangzhouCompleted
-
University Hospital Inselspital, BerneCantonal Hospital of St. Gallen; St. Claraspital AG; Cantonal Hospital of ZugTerminatedPancreatic CancerSwitzerland
-
Yonsei UniversityUnknownLocally Advanced Pancreatic CancerKorea, Republic of
-
University Hospital Inselspital, BerneTerminated
-
Assiut UniversityUnknown
-
University College London HospitalsUnknownProstate CancerUnited Kingdom
-
Poitiers University HospitalSport & Collection 2019WithdrawnCholangiocarcinoma | Interventional Imaging
-
Jewish General HospitalNot yet recruiting
-
University Hospital Inselspital, BerneTerminated
-
Memorial Sloan Kettering Cancer CenterCompletedColorectal Metastases to the LungUnited States