Liver CancerPhase 1/2ECT-HCCNCT02291133

Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)

A Phase 1/2 study testing Electrochemotherapy, Cliniporator Vitae® and Bleomycin PHC 15 e. (United States Pharmacopeia - USP) in people with Liver Cancer, run by Masa Bosnjak at 1 site in Slovenia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Liver Cancer
What is being tested?: Electrochemotherapy, Cliniporator Vitae® and Bleomycin PHC 15 e. (United States Pharmacopeia - USP)
Type of treatment: Injection or infusion, Medical device, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteSlovenia
Study dates: Jun 2014to Jan 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

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.

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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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

Slovenia1 site

University Medical Centre Ljubljana, Ljubljana, Slovenia
Ljubljana, 1000

Other trials in Slovenia

About this study

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.

Read the 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.

Conditions: Liver Cancer
Being tested: Electrochemotherapy, Cliniporator Vitae®, Bleomycin PHC 15 e. (United States Pharmacopeia - USP)
Keywords: Primary liver tumors, Bleomycin, Electrochemotherapy
Medical subject headings: Liver Neoplasms

What participants receive

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

ElectrochemotherapyProcedure or surgery
Exploration, anesthesia, adhesiolysis, mobilization of liver, intra-operative US or CT, bleomycin administration, electroporation
Cliniporator Vitae®Device
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.
Bleomycin PHC 15 e. (United States Pharmacopeia - USP)Drug
Intravenous in bolus administration of bleomycin (15 mg/m2)

Study groups in NCT02291133
Study group	Role	What they receive
Electrochemotherapy treatment	Experimental	Not described Receives: Procedure: Electrochemotherapy; Device: Cliniporator Vitae®; Drug: Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

What is being measured

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

Number of Participants With Toxicity Related to Electrochemotherapy
Biochemistry, blood test and/or US
Measured: After operation on day 7

Secondary outcomes (1)

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

Timeline

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

Jun 2014Jan 2020

First posted14 Nov 2014 (estimated)
Study startJun 2014
Primary completionSep 2019
Study completionJan 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Liver CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02291133
Sponsor's protocol ID: 21K/02/14
Acronym: ECT-HCC
Status last verified: Jul 2021
First submitted: 6 Nov 2014
Last updated: 23 Jul 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 24782355

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Liver Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)
ClinicalTrials.gov ID: NCT02291133
Acronym / sponsor ID: ECT-HCC / 21K/02/14
Conditions: Liver Cancer
Keywords: Primary liver tumors, Bleomycin, Electrochemotherapy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Masa BosnjakUniversity, hospital or other
Collaborators: Institute of Oncology Ljubljana, University of Ljubljana
Study start: Jun 2014
Primary completion: Sep 2019 (actual)
Study completion: Jan 2020 (actual)
First posted: 14 Nov 2014 (estimated)
Results: Posted 23 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

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

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Electrochemotherapy treatment	Experimental	Procedure: Electrochemotherapy, Device: Cliniporator Vitae®, Drug: Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

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.

Key exclusion criteria (15 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ElectrochemotherapyExploration, anesthesia, adhesiolysis, mobilization of liver, intra-operative US or CT, bleomycin administration, electroporation	Procedure or surgery	Electrochemotherapy treatment
Cliniporator Vitae®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.	Device	Electrochemotherapy treatment
Bleomycin PHC 15 e. (United States Pharmacopeia - USP)Intravenous in bolus administration of bleomycin (15 mg/m2)	Drug	Electrochemotherapy treatment

Primary outcome

Number of Participants With Toxicity Related to Electrochemotherapy
Time frame: After operation on day 7
Biochemistry, blood test and/or US

1 secondary outcome

Clinical Response Evaluation According to RECIST v1.1
Time frame: After operation on days 1, 7, 30, 60, 90, 120

Results and safety

Results posted to the registry on 23 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Electrochemotherapy Treatment	25	24

Primary outcome: Number of Participants With Toxicity Related to Electrochemotherapy

Time frame: After operation on day 7. Count of participants. Unit: Participants

Measure	Electrochemotherapy Treatment n = 24
No adverse events	20
ECT-related adverse events	0
Non-ECT-related within 24 h	0
Non-ECT-related after 24 h	4

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 7, 30, 60, 90, 120 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Electrochemotherapy Treatment	0 of 24 (0%)	15 of 24 (62.5%)	0 of 24

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24782355Edhemovic 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mihajlo Djokic, MD principal investigator

University Medical Centre Ljubljana, Ljubljana, Slovenia

Blaz Trotovsek, MD, PhD principal investigator

University Medical Centre Ljubljana, Ljubljana, Slovenia

Gregor Sersa, PhD study director

Institute of Oncology Ljubljana, Slovenia

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Electrochemotherapy, Cliniporator Vitae® and Bleomycin PHC 15 e. (United States Pharmacopeia - USP) in people with Liver Cancer, run by Masa Bosnjak at 1 site in Slovenia.

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 15 inclusion and 15 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: finished, as of the sponsor's last update on 23 Jul 2021. 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 Slovenia. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Yes. Results are posted in the registry (first posted 23 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Toxicity Related to Electrochemotherapy (time frame: After operation on day 7). 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 NCT02291133, which also lists 1 linked publication.

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 23 Jul 2021.