2022-500045-25-00
Current information on the trial

Trial details

Trial identifiers

Clinical trial identifiers
Calcium electroporation in combination with irreversible electroporation and immunotherapy in patients with pMMR metastatic colorectal cancer - A prospective, phase 2 study

Calcium electroporation in combination with irreversible electroporation and immunotherapy in patients with pMMR metastatic colorectal cancer
Public title (additional languages) Translation
Danish Effekt af elektroporation og immunterapi til patienter med tyk- og endetarmskræft med fjernspredning

010222
Secondary identifying numbers


Additional registries
Registry name Registry identifier

Trial information

Cover letter
Confidential information not for publication according to Regulation (EU) 536/2014

Attached documents
TitleFile typeDocument Type
Cover letterPDF Cover letter (for publication)
trial_info_compliance_with_regulation_title_lbl
Attached documents
TitleFile typeDocument Type
Compliance with regulation EU 2016-679 signedPDF Compliance with Regulation (EU) 2016/679 (for publication)
Trial category



Therapeutic exploratory (Phase II)

Category 2

This is a phase II, investigator-initiated study, involving CE approved devices and an EMA approved drug.
Medical condition
Medical condition (English) Medical condition (languages) Is the medical condition considered to be a rare disease?
Colorectal cancer Danish:Tyk- og endetarmskræft No

Diseases [C] - Neoplasms [C04]
Medical condition(s) MedDRA information
Version Level Classification code Term name System organ class
21.0 PT 10010035 Colorectal cancer stage IV 100000004864
Main objective
Safety,Efficacy,Therapy

The main objective is to determine the efficacy and safety of Ca-EP performed concurrently with IRE followed by a PD-1 inhibitor (pembrolizumab).

Secondary objective
Number Secondary objective (English) Secondary objective (additional languages)
1 To demonstrate how the treatment affects the local and systemic immune response measured by both blood samples and tumor biopsies.
Eligibility criteria

Principal inclusion criteria

Number Principal inclusion criteria (English) Principal inclusion criteria (additional languages)
1 Signed informed consent
10 Adequate bone marrow function: • Hemoglobin ≥ 5.6 mmol/L or ≥ 9 g/dL, • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L • 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 • Alanine aminotransferase (ALT): ≤2.5 X ULN or ≤5 X ULN for subjects with liver metastases • Aspartate aminotransferase (AST): ≤2.5 X ULN or ≤5 X ULN for subjects with liver metastases • 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 • 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.
2 Age ≥ 18 years of age
3 Histologically confirmed stage IV, non-resectable pMMR colorectal cancer
4 The primary malignant tumor is left sided (cancer of the splenic flexure and cancer in regions distal to the splenic flexure, including the rectum)
5 The primary tumor is described as reachable at index endoscopy
6 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
7 Previous chemotherapy a), or b): a) 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) b) 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 o 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

Principal exclusion criteria

Number Principal exclusion criteria (English) Principal exclusion criteria (additional languages)
1 Prior treatment with an immune checkpoint inhibitor (e.g., anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or anti-CTLA-4 agent)
10 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
11 Relative contraindications for IRE: • Atrial fibrillation • Combined severe stenosis of the common hepatic artery and main portal vein branch
2 Concurrent treatment with an investigational medicinal product
3 Radiotherapy or major surgery within the last two weeks prior to entering the study
4 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
5 Patients should be excluded if they have an active, known or suspected autoimmune disease (except thyroiditis with replacement therapy and type I diabetes mellitus).
6 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).
7 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.
8 Allergies and Adverse Drug Reaction: • History of allergy to study drug components • History of severe hypersensitivity reaction to any monoclonal antibody
9 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
End points

Primary end points

Number Primary end points (English) Primary end points (additional languages)
1 To evaluate the safety and tolerability of Ca-EP and IRE in combination with pembrolizumab

Secondary end points

Number Secondary end points (English) Secondary end points (additional languages)
1 To evaluate the systemic response, measured by biopsy data from a metastasis not treated with IRE
2 To evaluate the efficacy of Ca-EP and IRE in combination with pembrolizumab
3 To evaluate tumor response per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1
4 To evaluate tumor response by dynamic contrast enhanced ultra sound (DCE-US)
5 To evaluate the phenotypic change of the TILs from the primary tumor by flow cytometry
6 To evaluate progression free survival
7 To evaluate overall survival
8 To evaluate quality of life (by questionnaire EORTC QLQ-C30)
Trial Duration
01/06/2022
01/06/2026

Source of monetary support or material support

Organisation name
Zealand University Hospital
Population of trial subjects
65+ years,18-64 years



Patients

Protocol information

Clinical Trial Protocol
Attached documents
TitleFile typeDocument Type
ProtocolPDF Protocol (for publication)

Attached documents
TitleFile typeDocument Type
ProtokolresumePDF Synopsis of the protocol (for publication)

There are no attached documents
Study design

Period details

Number Period title Period Description Allocation method Blinding used Roles blinded Blinding implementation details Arm details

There are no attached documents

Scientific Advice and Paediatric Investigation Plan

Scientific Advice

There are no attached documents
Paediatric Investigation Plan

There are no attached documents

Associated Clinical Trial

Associated Clinical Trial

References

Online References

Countries outside the European Economic Area

Countries outside the European Economic Area

Sponsors

NameOrganisation typeCountryTypeStatusLegal representativeScientific contact pointPublic contact pointThird parties
Zealand University HospitalHospital/Clinic/Other health care facilityDenmarkNon-CommercialActive Tobias Freyberg JustesenRegion Sjælland0

Products

Role: Test Name: KEYTRUDA 25 mg/mL concentrate for solution for infusion

EU MP number Marketing authorisation number Product authorisation Product name Pharmaceutical form Strength Sponsors product code Active substance name EU substance number ATC Name ATC Code ATC Level Sponsors substance code Active substance other descriptive name Type Exclude MSC
PRD4323105, PRD4323784, PRD4323785, PRD4323786 EU/1/15/1024/002 Authorised KEYTRUDA 25 mg/mL concentrate for solution for infusion SOLUTION FOR INFUSION Pembrolizumab 25mg PEMBROLIZUMAB SUB167136 - L01XC18 5 Product

Investigator Brochure for the Medicinal Product

There are no attached documents

Attached documents
TitleFile typeDocument Type
Keytruda - DanishPDF Summary of Product Characteristics (SmPC) (for publication)

Compliance with (GMP) for the Medicinal Product

There are no attached documents


There are no attached documents

IMPD Quality

Confidential information not for publication according to Regulation (EU) 536/2014

Confidential information not for publication according to Regulation (EU) 536/2014

The IMP (Keytruda) has an EMA marketing authorisation and the smPc is provided.

IMPD - Safety and Efficacy

There are no attached documents

There are no attached documents

The IMP (Keytruda) has an EMA marketing authorisation and the smPc is provided.

Role: Auxiliary Name: CALCIUM CHLORIDE HEXAHYDRATE

EU MP number Marketing authorisation number Product authorisation Product name Pharmaceutical form Strength Sponsors product code Active substance name EU substance number ATC Name ATC Code ATC Level Sponsors substance code Active substance other descriptive name Type Exclude MSC
Multiple EU MP number - Authorised CALCIUM CHLORIDE HEXAHYDRATE SOLUTION FOR INJECTION 1g / 10mL CALCIUM CHLORIDE HEXAHYDRATE SUB13169MIG - - - Substance DK

Compliance with (GMP) for the Medicinal Product

There are no attached documents


There are no attached documents

Auxiliary Medicinal Product Dossier

Confidential information not for publication according to Regulation (EU) 536/2014

Documents

Attached documents
TitleFile typeDocument Type
Cover letterPDF Cover letter (for publication)
Compliance with regulation EU 2016-679 signedPDF Compliance with Regulation (EU) 2016/679 (for publication)
ProtocolPDF Protocol (for publication)
ProtokolresumePDF Synopsis of the protocol (for publication)
Keytruda - DanishPDF Summary of Product Characteristics (SmPC) (for publication)
Produktdossier CalciumchloridPDF Auxiliary Medicinal Product Dossier (for publication)
Content labelling of the IMPPDF Content labelling of the IMPs (for publication)

Denmark - Authorised

Planned number of subjects

12

Clinical Trial Sites

Organisation name Site location Site street address Site city Site post code Site country Title First name Last name Department name Telephone number Email
Zealand University Hospital Sygehusvej 10 Sygehusvej 10 Roskilde 4000 Denmark 2 Ismail Gögenur Department of Surgery 26336426 igo@regionsjaelland.dk
Zealand University Hospital Lykkebaekvej 1 Lykkebaekvej 1 Koege 4600 Denmark 2 Ismail Gögenur Department of Surgery 26336426 igo@regionsjaelland.dk

Documents

Recruitment Arrangements

Attached documents
TitleFile typeDocument Type
Recruitment arrangementsPDF Recruitment arrangements (for publication)

Proof of payment of fee

There are no attached documents

Proof of insurance cover or identification

Attached documents
TitleFile typeDocument Type
Bekendtgørelse om dækningsområdet for lov om klage- og erstatningsadgang inden for sundhedsvæsenetPDF Proof of insurance (for publication)

Financial and other arrangements

Confidential information not for publication according to Regulation (EU) 536/2014

Suitability of the facilities

Attached documents
TitleFile typeDocument Type
Suitability of the facilitiesPDF Suitability of the clinical trial sites facilities (for publication)

Subject Information

Attached documents
TitleFile typeDocument Type
DeltagerinformationPDF Subject information and informed consent form (for publication)
SamtykkeerklæringPDF Subject information and informed consent form (for publication)

Suitability of Investigator

Attached documents
TitleFile typeDocument Type
Investigator CV - Ismail GögenurPDF Investigator CV (for publication)

There are no attached documents

Compliance with national requirements on Data Protection

There are no attached documents

Compliance with use of Biological samples

There are no attached documents

All Documents

Attached documents
TitleFile typeDocument Type
DeltagerinformationPDF Subject information and informed consent form (for publication)
Bekendtgørelse om dækningsområdet for lov om klage- og erstatningsadgang inden for sundhedsvæsenetPDF Proof of insurance (for publication)
SamtykkeerklæringPDF Subject information and informed consent form (for publication)
Investigator CV - Ismail GögenurPDF Investigator CV (for publication)
Recruitment arrangementsPDF Recruitment arrangements (for publication)
Suitability of the facilitiesPDF Suitability of the clinical trial sites facilities (for publication)