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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Exploration, anesthesia, adhesiolysis, mobilization of liver, intra-operative US or CT, bleomycin administration, electroporation
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.
Intravenous in bolus administration of bleomycin (15 mg/m2)
University Medical Centre Ljubljana, Ljubljana, Slovenia
Ljubljana, Slovenia
Number of Participants With Toxicity Related to Electrochemotherapy
Biochemistry, blood test and/or US
Time frame: After operation on day 7
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
Time frame: After operation on days 1, 7, 30, 60, 90, 120
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