Trial Outcomes & Findings for Treatment of Liver Metastases With Electrochemotherapy (NCT NCT01264952)

NCT ID: NCT01264952

Last Updated: 2020-11-24

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: After operation on day 7
• Results posted on: 2020-11-24

Participant Flow

Participant milestones

Measure	Bilateral, Multiple, Metachronous Metastases The first group included patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Synchronous Metastases The second group (group II) included patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	<= 3 Metachronous, Unresectable Liver Metastases The third group included patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Overall Study STARTED	6	2	8
Overall Study COMPLETED	6	2	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment of Liver Metastases With Electrochemotherapy

Baseline characteristics by cohort

Measure	Group I n=6 Participants Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=2 Participants Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=8 Participants Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	12 Participants n=4 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Age, Continuous	60.0 years STANDARD_DEVIATION 6.4 • n=5 Participants	45.5 years STANDARD_DEVIATION 19.1 • n=7 Participants	57.3 years STANDARD_DEVIATION 10.7 • n=5 Participants	56.8 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Slovenia	6 participants n=5 Participants	2 participants n=7 Participants	8 participants n=5 Participants	16 participants n=4 Participants

PRIMARY outcome

Timeframe: After operation on day 7

Outcome measures

Measure	Group I n=6 Participants Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=2 Participants Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=8 Participants Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Evaluation of Toxicity Related to Electrochemotherapy (Toxicity, Symptoms)	0 events	0 events	0 events

SECONDARY outcome

Timeframe: After operation on tha days 2, 7, 30, monthly

Outcome measures

Measure	Group I n=6 Participants Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=2 Participants Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=8 Participants Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Number of Participants With Non-Serious Adverse Events	3 patients with non-severe adverse events	2 patients with non-severe adverse events	7 patients with non-severe adverse events

SECONDARY outcome

Timeframe: After operation or 1st day after operation, 7th day, 30th day, monthly

Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:

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

Outcome measures

Measure	Group I n=12 metastases Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=1 metastases Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=14 metastases Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Treatment Evaluation of Tumor Response - Measurements of Tumor Lesions by Contrast Enhanced Ultrasonography (US-Doppler), Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Histology	10 metastases	1 metastases	10 metastases

Adverse Events

Group I

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Group II

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Group III

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Group I n=6 participants at risk Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=2 participants at risk Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=8 participants at risk Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Gastrointestinal disorders Small bowl obstruction	0.00% 0/6	0.00% 0/2	12.5% 1/8
Gastrointestinal disorders Colon perforation	16.7% 1/6	0.00% 0/2	12.5% 1/8
Gastrointestinal disorders Abdominal abcess	0.00% 0/6	50.0% 1/2	12.5% 1/8

Other adverse events

Measure	Group I n=6 participants at risk Patients with bilateral, multiple, metachronous metastases in whom standard treatment included twostage liver resection, due to the extent of the disease and/or their general condition. During the first operation, right portal vein was ligated and metastases on the left side were excised or ablated with radiofrequency ablation. At the same time, up to three metastases on the right side were treated with electrochemotherapy. During the second operation, both treated and non-treated metastases on the right side were removed with right hemihepatectomy.	Group II n=2 participants at risk Patients with synchronous metastases, but their general condition and extent of the disease did not allow simultaneous removal of the primary tumor and metastases. During the first operation, the primary tumor was removed (colorectal resection) and some of the liver metastases were treated by electrochemotherapy. About 6 weeks later, during the second operation for liver metastases, both treated and non-treated metastases were removed with liver resection.	Group III n=8 participants at risk Patients with up to three metachronous, unresectable liver metastases, demanding too excessive resection, or untreatable by standard thermal ablative methods, due to the close proximity of major blood vessels. Electrochemotherapy was offered to these patients as the only treatment option.
Infections and infestations Infection NOS	50.0% 3/6	50.0% 1/2	75.0% 6/8
Infections and infestations Fever	33.3% 2/6	0.00% 0/2	0.00% 0/8
Cardiac disorders Atrial fibrilation	16.7% 1/6	0.00% 0/2	0.00% 0/8
Vascular disorders Pulmonary hypertension	16.7% 1/6	0.00% 0/2	0.00% 0/8
Infections and infestations Pneumonia	0.00% 0/6	50.0% 1/2	0.00% 0/8
Skin and subcutaneous tissue disorders Wound infection	0.00% 0/6	50.0% 1/2	0.00% 0/8
Gastrointestinal disorders Ascites	0.00% 0/6	0.00% 0/2	25.0% 2/8
Cardiac disorders Supraventricular tachycardia	0.00% 0/6	0.00% 0/2	12.5% 1/8
Hepatobiliary disorders Transient liver failure	0.00% 0/6	50.0% 1/2	25.0% 2/8
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6	0.00% 0/2	12.5% 1/8
Hepatobiliary disorders Cholestatic icterus	0.00% 0/6	0.00% 0/2	12.5% 1/8
Hepatobiliary disorders Biliary fistula	0.00% 0/6	0.00% 0/2	25.0% 2/8

Additional Information

Gregor Sersa, PhD

Institute of Oncology Ljubljana

Phone: +386 1 5879 434

Email: gsersa@onko-i.si

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place