Treatment of Primary Liver Tumors With Electrochemotherapy (ECT)

NCT02291133 | Completed Phase 1 Results DMC

• 1 other identifier: 21K/02/14
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Cancer

Keywords

Primary liver tumors; Bleomycin; Electrochemotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Toxicity Related to Electrochemotherapy

  Biochemistry, blood test and/or US

  After operation on day 7

Secondary Outcomes (1)

• Clinical Response Evaluation According to RECIST v1.1

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

Study Arms (1)

Electrochemotherapy treatment

EXPERIMENTAL

Procedure: Electrochemotherapy; Device: Cliniporator Vitae®; Drug: Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

Interventions

Electrochemotherapy PROCEDURE

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

Electrochemotherapy treatment

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.

Electrochemotherapy treatment

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

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

Electrochemotherapy treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masa Bosnjak: lead
• Institute of Oncology Ljubljana: collaborator
• University of Ljubljana: collaborator

Study Sites (1)

University Medical Centre Ljubljana, Ljubljana, Slovenia

Ljubljana, 1000, Slovenia

Location

Related Publications (1)

• 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.

  PMID: 24782355 BACKGROUND

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Electrochemotherapy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Electroporation Therapies; Electroporation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Results Point of Contact

• Title: Dr Gregor Serša
• Organization: Institute of Oncology Ljubljana

gsersa@onko-i.si

+38615874343

Study Officials

• Mihajlo Djokic, MD

  University Medical Centre Ljubljana, Ljubljana, Slovenia

  PRINCIPAL INVESTIGATOR

• Blaz Trotovsek, MD, PhD

  University Medical Centre Ljubljana, Ljubljana, Slovenia

  PRINCIPAL INVESTIGATOR

• Gregor Sersa, PhD

  Institute of Oncology Ljubljana, Slovenia

  STUDY DIRECTOR

• Borut Stabuc, MD, PhD

  University Medical Centre Ljubljana, Ljubljana, Slovenia

  STUDY DIRECTOR

• Dragoje Stanisavljevic, MD

  University Medical Centre Ljubljana, Ljubljana, Slovenia

  STUDY CHAIR

• Valentin Sojar, MD, PhD

  University Medical Centre Ljubljana, Ljubljana, Slovenia

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, MPharm

Study Record Dates

• First Submitted: November 6, 2014
• First Posted: November 14, 2014
• Study Start: June 1, 2014
• Primary Completion: September 1, 2019
• Study Completion: January 1, 2020
• Last Updated: July 23, 2021
• Results First Posted: July 23, 2021

Record last verified: 2021-07

Locations

SL (1)