Treatment of Liver Metastases With Electrochemotherapy

NCT ID: NCT01264952

Last Updated: 2020-11-24

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2013-11-30

Brief Summary

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The aim of the study is to evaluate toxicity and effectiveness of electrochemotherapy with bleomycin in treatment of liver metastases of colorectal cancer in clinical study phase I and II.

The study will include 10-15 patients with colorectal cancer with synchronous or metachronous liver metastases, but electrochemotherapy will be performed on metastasis not more than 3 cm in the largest diameter.

Treatment effectiveness will be evaluated by magnetic resonance imaging (MRI) and ultrasonography (US) in a monthly interval. Two or three month after the first operation the treated and untreated metastases will be resected and through histological analyses performed.

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

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The study will be conducted on patients with colorectal cancer with synchronous or metachronous liver metastases. Included will be 10-15 patients.

Predominantly, patients with synchronous metastases will be included into the study. These patients present liver metastases at the time of primary tumor resection. Electrochemotherapy will be performed on one metastasis not more than 3 cm in largest diameter at the time of the primary tumor operation, but patients have to have at least 2 to 8 metastases. These metastases will be aimed to be resected in the following operation. It is a standard procedure that liver metastases are resected 2-3 months after the primary tumor resection, in the meantime they are on standard chemotherapeutic protocol (FOLFOX, FOLFIRI, Capecitabine). Only in the case of solitary metastasis smaller than 3 cm in diameter, it is resected during the resection of the primary tumor. In the study additional antitumor effectiveness of electrochemotherapy to other treatment (chemotherapy) will be evaluated, compared to non-electrochemotherapy treated metastases. Treatment effectiveness will be evaluated by magnetic resonance imaging (MRI) and ultrasonography (US), in a monthly interval. Two to three month after the first operation the treated and untreated metastases will be resected and thorough histological analysis performed.

The second group of patients will be with metachronous liver metastases not larger than 3 cm in diameter, that location is in the vicinity of hollow liver structures and would not be possible to resect them without extensive and potentially jeopardizing liver resection. One of them will be treated by electrochemotherapy. In a month interval treatment effectiveness will be evaluated by MRI. In the case that metastases will decrease in size and to the situation that metastases are resectable, second operation will be performed, metastases resected and thorough histopathological evaluation performed. Otherwise standard treatment procedure will be performed (chemotherapy).

All patients will be treated after the procedure is thoroughly described to them, and have signed informed consent.

Conditions

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Liver Metastases

Keywords

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Liver metastases of colorectal cancer Bleomycin Electrochemotherapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Electrochemotherapy

Treatment procedure: anesthesia, positioning of electrodes, intravenous in bolus administration of bleomycin (15 mg/m2), within 5-30 min after administration of bleomycin application of electric pulses (8 pulses, duration 100 microseconds, frequency 4 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.

Intervention Type PROCEDURE

Other Intervention Names

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Device: Cliniporator Vitae® Drug: Bleomicin PHC 15 e. (United States Pharmacopeia - USP)

Eligibility Criteria

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Inclusion Criteria

* Patients with measurable liver metastases, presented simultaneously with primary tumor, aimed at primary tumor resection and in a 2-3 month interval resection of liver metastases. One metastasis will be treated by electrochemotherapy, not larger than 3 cm in diameter.
* Metastasis has to be accessible for application of electrochemotherapy during the operation, without major liver manipulation or mobilization in order not to create situation that would hamper feasibility of the second operation; resection of metastases.
* Patients with metachronous liver metastases, that are positioned in unresectable liver area, near blood vessels, but inoperable patients.
* Recurrent liver metastases, not more than 3, that are not larger than 3 cm in diameter.
* Histologically and cytologically confirmed cancer, any histological differentiation.
* Life expectancy more than 3 month.
* Performance status Karnofsky ≥ 70 or (World Health Organization) WHO ≥ 2.
* Age more than 18.
* The patient must be offered standard treatment.
* Electrochemotherapy is offered to the patients in the case of the disease progression during the standard treatment, in the case or metastases recurrence, or when they refuse standard treatment.
* 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.

Exclusion Criteria

* Metastases more than 3 cm in diameter.
* Synchronous unresectable metastases.
* Metachronous unresectable metastases or bigger than 3 cm in diameter.
* Visceral, bone or diffuse metastases.
* Coagulation disturbances.
* Allergic reaction to bleomycin, or cumulative dose of 250 mg/m2 bleomycin received.
* Impaired kidney function (creatinin \> 150 µmol/l).
* Patients with hearth failure or pace maker.
* Patients with epilepsy.
* Secondary primary tumor, except surgically treated noninvasive cancer of cervix, or surgically or irradiated basal cell carcinoma.
* Pregnancy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Medical Centre Ljubljana

OTHER

Sponsor Role collaborator

Institute of Oncology Ljubljana

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eldar Gadzijev, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Oncology Ljubljana, Department of Surgical Oncology, Ljubljana, Slovenia

Gregor Sersa, PhD (Biol.)

Role: STUDY_DIRECTOR

Institute of Oncology Ljubljana, Department of Experimental Oncology, Ljubljana, Slovenia

Locations

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Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Site Status

Countries

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Slovenia

References

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Edhemovic I, Gadzijev EM, Brecelj E, Miklavcic D, Kos B, Zupanic A, Mali B, Jarm T, Pavliha D, Marcan M, Gasljevic G, Gorjup V, Music M, Vavpotic TP, Cemazar M, Snoj M, Sersa G. Electrochemotherapy: a new technological approach in treatment of metastases in the liver. Technol Cancer Res Treat. 2011 Oct;10(5):475-85. doi: 10.7785/tcrt.2012.500224.

Reference Type DERIVED
PMID: 21895032 (View on PubMed)

Other Identifiers

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03-Z 16/KSOPKR-6

Identifier Type: -

Identifier Source: org_study_id