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Treatment of Primary Liver Tumors With Electrochemotherapy (ECT) (ECT-HCC)

Primary Purpose

Liver Cancer

Status

Completed

Phase

Phase 1

Locations

Slovenia

Study Type

Interventional

Intervention

Electrochemotherapy

Cliniporator Vitae®

Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

About this trial

This is an interventional treatment trial for Liver Cancer focused on measuring Primary liver tumors, Bleomycin, Electrochemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with primary liver tumors; hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other primary tumors not larger than 7 cm that are positioned in unresectable liver area, near blood vessels in operable patients.
Patients with the progression of the disease (confirmed by radiological imaging) after treatment with TACE, RFA or percutaneous alcohol ablation, which are not suitable for potentially curative treatment, but with relatively good "performance status" and Child-Pugh score < 8.
Patients from group 1. and 2. are patients, in whom standard treatment procedures are not eligible, so ECT will be the only therapeutic option. In patients with multiple liver tumors, unresectable tumors which are also unsuitable for RAF will be treated by ECT, whereas other tumors will be resected or treated by RAF.
Patients with tumors smaller tumors, not suitable for liver transplantation, but also unsuitable for RFA treatment or percutaneous alcohol ablation because of the position of the tumor. Electrochemotherapy will be as bridge therapy, till liver transplantation.
Patients with tumors> 4 cm in diameter, in difficult to reach locations, and patients unsuitable for treatment with other treatment options.
Patients from group 3. and 4. are patients, potentially curable with standard treatment. Electrochemotherapy in these patients will not affect the standard of care of these patients, recommended in guidelines for HCC.
Electrochemotherapy is offered to the patients also when they refuse standard treatments.
Histologically confirmed primary liver cancer and/or based on radiological imaging laboratory tests confirmed primary liver cancer by multidisciplinary team for liver tumors.
Age more than 18.
Life expectancy more than 3 month.
Performance status Karnofsky ≥ 70 or (World Health Organization) WHO < or 2.
Treatment free interval 2-5 weeks, depending on the drugs used.
Patient must be mentally capable of understanding the information given.
Patient must give informed consent.
Patient must be discussed at the multidisciplinary team for liver tumors before entering the trial.

Exclusion Criteria:

Secondary primary tumor, except surgically treated noninvasive cancer of cervix, or surgically or irradiated basal cell carcinoma
Visceral, bone or diffuse metastases.
Life-threatening infection and/or heart failure and/or liver failure and/or other severe systemic pathologies.
Clinically significant ascites.
Significant reduction in respiratory function.
Age less than 18 years.
Coagulation disturbances (those who do not respond on standard treatment with vitamin-K or fresh frozen plasma).
Cumulative dose of 250 mg/m2 bleomycin received.
Allergic reaction to bleomycin.
Impaired kidney function (creatinin > 150 µmol/l).
Patients with epilepsy.
Patients with arrhythmias.
Patients with heart failure or pace maker.
Pregnancy.
Patient incapable of understanding the aim of the study or disagree with the entering into the clinical study.

Sites / Locations

University Medical Centre Ljubljana, Ljubljana, Slovenia

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Electrochemotherapy treatment

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Toxicity Related to Electrochemotherapy

Biochemistry, blood test and/or US

Secondary Outcome Measures

Clinical Response Evaluation According to RECIST v1.1

Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Full Information

NCT ID

NCT02291133

First Posted

November 6, 2014

Last Updated

July 2, 2021

Sponsor

Masa Bosnjak

Collaborators

Institute of Oncology Ljubljana, University of Ljubljana

1. Study Identification

Unique Protocol Identification Number

NCT02291133

Brief Title

Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)

Acronym

ECT-HCC

Official Title

Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Completed

Study Start Date

June 2014 (undefined)

Primary Completion Date

September 2019 (Actual)

Study Completion Date

January 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Masa Bosnjak

Collaborators

Institute of Oncology Ljubljana, University of Ljubljana

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The aim of the study is to evaluate toxicity and effectiveness of electrochemotherapy with bleomycin in treatment of primary liver tumors in clinical study phase I and II. The study will include 10 patients in phase I clinical study and additional 15 patients in phase II clinical study (or in the extension of the clinical study), which will fulfill inclusion criteria. Treatment effectiveness will be evaluated by DCE-US or CT perfusion, to detect early events in tumor perfusion after ECT compared to tumor perfusion before ECT. Long term effectiveness of the treatment will be evaluated by modified RECIST criteria, which will take into account difference in size and density, determined from images obtained by CT perfusion of the treated tumor nodules before and after ECT. Tumor volume will be calculated by following formula , where a will be shorter and b longer tumor diameter. The secondary objectives of the trial are to quantify the impact of the treatment on the patient's quality of life, tolerance to the therapy and suitability for larger study to be conducted.

Detailed Description

The study will be conducted on patients with primary liver tumors. 10 patients will be included in phase I clinical study and additional 15 patients in phase II clinical study (or in the extension of the clinical study). Depending on the position of tumors, appropriate electrodes will be selected; hexagonal needle electrodes with fixed geometry for tumors not larger than 3 cm in diameter, where lower edge of the tumor is located up to 3 cm below the liver capsule or longer single needle electrodes. Individual electrodes, positioned according to the prepared treatment plan will be used for tumors up to 7 cm in diameter, or located near vena cava or large hepatic or portal veins. Electrochemotherapy will be performed within 8-28 min after intravenous in bolus administration of bleomycin (15 mg/m2). Triggering of electric pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. All patients will be treated after the procedure has been thoroughly described to them, and have signed informed consent.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cancer

Keywords

Primary liver tumors, Bleomycin, Electrochemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Electrochemotherapy treatment

Arm Type

Experimental

Intervention Type

Procedure

Intervention Name(s)

Electrochemotherapy

Intervention Description

Exploration, anesthesia, adhesiolysis, mobilization of liver, intra-operative US or CT, bleomycin administration, electroporation

Intervention Type

Device

Intervention Name(s)

Cliniporator Vitae®

Intervention Description

Positioning of electrodes, 8-28 min after administration of bleomycin application of electric pulses (8 pulses, duration 100 microseconds, frequency 8 Hz with amplitude adequate to cover the whole treated lesion with electric field necessary for reversible plasma membrane permeabilization), removal of electrodes. The maximum duration of procedure is 90 minutes, after liver mobilization.

Intervention Type

Drug

Intervention Name(s)

Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

Intervention Description

Intravenous in bolus administration of bleomycin (15 mg/m2)

Primary Outcome Measure Information:

Title

Number of Participants With Toxicity Related to Electrochemotherapy

Description

Biochemistry, blood test and/or US

Time Frame

After operation on day 7

Secondary Outcome Measure Information:

Title

Clinical Response Evaluation According to RECIST v1.1

Description

Time Frame

After operation on days 1, 7, 30, 60, 90, 120

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with primary liver tumors; hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other primary tumors not larger than 7 cm that are positioned in unresectable liver area, near blood vessels in operable patients. Patients with the progression of the disease (confirmed by radiological imaging) after treatment with TACE, RFA or percutaneous alcohol ablation, which are not suitable for potentially curative treatment, but with relatively good "performance status" and Child-Pugh score < 8. Patients from group 1. and 2. are patients, in whom standard treatment procedures are not eligible, so ECT will be the only therapeutic option. In patients with multiple liver tumors, unresectable tumors which are also unsuitable for RAF will be treated by ECT, whereas other tumors will be resected or treated by RAF. Patients with tumors smaller tumors, not suitable for liver transplantation, but also unsuitable for RFA treatment or percutaneous alcohol ablation because of the position of the tumor. Electrochemotherapy will be as bridge therapy, till liver transplantation. Patients with tumors> 4 cm in diameter, in difficult to reach locations, and patients unsuitable for treatment with other treatment options. Patients from group 3. and 4. are patients, potentially curable with standard treatment. Electrochemotherapy in these patients will not affect the standard of care of these patients, recommended in guidelines for HCC. Electrochemotherapy is offered to the patients also when they refuse standard treatments. Histologically confirmed primary liver cancer and/or based on radiological imaging laboratory tests confirmed primary liver cancer by multidisciplinary team for liver tumors. Age more than 18. Life expectancy more than 3 month. Performance status Karnofsky ≥ 70 or (World Health Organization) WHO < or 2. Treatment free interval 2-5 weeks, depending on the drugs used. Patient must be mentally capable of understanding the information given. Patient must give informed consent. Patient must be discussed at the multidisciplinary team for liver tumors before entering the trial. Exclusion Criteria: Secondary primary tumor, except surgically treated noninvasive cancer of cervix, or surgically or irradiated basal cell carcinoma Visceral, bone or diffuse metastases. Life-threatening infection and/or heart failure and/or liver failure and/or other severe systemic pathologies. Clinically significant ascites. Significant reduction in respiratory function. Age less than 18 years. Coagulation disturbances (those who do not respond on standard treatment with vitamin-K or fresh frozen plasma). Cumulative dose of 250 mg/m2 bleomycin received. Allergic reaction to bleomycin. Impaired kidney function (creatinin > 150 µmol/l). Patients with epilepsy. Patients with arrhythmias. Patients with heart failure or pace maker. Pregnancy. Patient incapable of understanding the aim of the study or disagree with the entering into the clinical study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mihajlo Djokic, MD

Organizational Affiliation

University Medical Centre Ljubljana, Ljubljana, Slovenia

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Blaz Trotovsek, MD, PhD

Organizational Affiliation

University Medical Centre Ljubljana, Ljubljana, Slovenia

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Gregor Sersa, PhD

Organizational Affiliation

Institute of Oncology Ljubljana, Slovenia

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Borut Stabuc, MD, PhD

Organizational Affiliation

University Medical Centre Ljubljana, Ljubljana, Slovenia

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Dragoje Stanisavljevic, MD

Organizational Affiliation

University Medical Centre Ljubljana, Ljubljana, Slovenia

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Valentin Sojar, MD, PhD

Organizational Affiliation

University Medical Centre Ljubljana, Ljubljana, Slovenia

Official's Role

Study Chair

Facility Information:

Facility Name

University Medical Centre Ljubljana, Ljubljana, Slovenia

City

Ljubljana

ZIP/Postal Code

1000

Country

Slovenia

12. IPD Sharing Statement

Citations:

PubMed Identifier

24782355

Citation

Edhemovic I, Brecelj E, Gasljevic G, Marolt Music M, Gorjup V, Mali B, Jarm T, Kos B, Pavliha D, Grcar Kuzmanov B, Cemazar M, Snoj M, Miklavcic D, Gadzijev EM, Sersa G. Intraoperative electrochemotherapy of colorectal liver metastases. J Surg Oncol. 2014 Sep;110(3):320-7. doi: 10.1002/jso.23625. Epub 2014 Apr 30.

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Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)

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