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Metastatic Colorectal CancerPhase 2ELINCT05609656

Electroporation and Immunotherapy in Metastatic Colorectal Cancer

A Phase 2 study testing Irreversible electroporation, Calcium electroporation and Pembrolizumab in people with Metastatic Colorectal Cancer, run by Ismail Gögenur at 1 site in Denmark.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Irreversible electroporation, Calcium electroporation and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteDenmark
Study dates
26 Jan 2023to 2 May 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 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:
  • 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:
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or creatinine ≤1.5 X upper limit of normal (ULN)
  • 12. Adequate liver function:
  • 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:
  • 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.

Who cannot join

  • 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
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  • 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:
  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Zealand University Hospital

    Køge, 4600

Other trials in Denmark

About this study

Official title: 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

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).

Read the detailed description

The investigators hypothesize that Ca-EP targeting the primary CRC tumor combined with IRE targeting a metastasis will be a promising, safe two target approach to ensure sufficient immune response both locally and systemic to potentiate the efficacy of immunotherapy in patients with pMMR metastatic CRC.

Being tested
Irreversible electroporation, Calcium electroporation, Pembrolizumab
Keywords
Irreversible electroporation, Calcium electroporation, Pembrolizumab, Abscopal effect
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Irreversible electroporationDevice

    Also called (IRE)

    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.

  • Calcium electroporationDevice

    Also called (CaEP)

    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.

  • PembrolizumabDrug

    Also called Keytruda

    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).

Study groups in NCT05609656
Study groupRoleWhat they receive
IRE + CaEP + PembrolizumabExperimentalIrreversible 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.
Receives: Device: Irreversible electroporation; Device: Calcium electroporation; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Safety of electroporation and immunotherapy according to CTCAE v. 4.0

    Measured: up to 1 month after end of treatment

Secondary outcomes (4)

  1. Tumor response by CT

    Based on CT chest/abdomen scans according to RECIST version 1.1

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

  2. Tumor response by ultrasound

    Based on contrast enhanced ultrasound (CEUS) utilizing the standardized and quantitative method Dynamic CEUS (DCEUS)

    Measured: Baseline compared to 2 months after start of treatment

  3. Progression free survival

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

  4. Overall survival

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2022
  2. Study start26 Jan 2023
  3. Primary completion8 Apr 2024
  4. Study completion2 May 2024

Why it stopped: The study was terminated on the basis on an evaluation of the efficacy and safety of the 4 included and treated patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05609656
Sponsor's protocol ID
2022-500045-25-00
Acronym
ELI
Status last verified
May 2024
First submitted
27 Oct 2022
Last updated
3 Jun 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Irreversible electroporation, Calcium electroporation and Pembrolizumab in people with Metastatic Colorectal Cancer, run by Ismail Gögenur at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated on the basis on an evaluation of the efficacy and safety of the 4 included and treated patients.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The incidence rate of adverse events according to CTCAE v. 4.0 (time frame: up to 1 month after end of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05609656.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2024.

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