The primary objective of this study is to evaluate the safety in terms of complication rate of IRE in the treatment of colorectal liver metastasis/es
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Metastases
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome is the safety of the IRE procedure using the NanoKnife.
Secondary outcome
Secondary outcomes are feasibility (including procedure time), size and shape
of ablated area and the extent of cellular damage and apoptosis.
Background summary
Colorectal carcinoma is one of the most common malignancies in the Western
world. 40-60% of the patients develop liver metastases in the course of the
disease. Surgical resection is still the treatment of choice, but unfortunately
up to 70% of the patients are not eligible for this treatment (1-3). Selected
patients are offered thermal ablation therapy, such as RFA and microwave
ablation. In recent years, SBRT has also emerged as a promising alternative.
However, all these treatment modalities have their own shortcomings and the
search for new local treatment techniques is ongoing.
Irreversible electroporation (IRE) is an ablation technique that takes
advantage of the electric potential gradient that exists across cell membranes.
The application of an electric field across a cell alters the transmembrane
potential. On reaching a specific voltage, the bilayer structure of the cell
membrane is permanently disrupted, inducing apoptosis. Recent findings
resulting from animal studies using IRE on normal tissue show a sharply
demarcated treatment area, with preservation of the - acellular - connective
tissue architecture and major blood vessels in the ablated area. This is in
contrast to thermal ablation techniques, where denaturation of proteins causes
disruption of the connective tissue, destroying the anatomical framework. Being
non-thermal, the technique may not be susceptible to non-uniform ablation zones
due to the 'heat-sink' effect (where tumor cells adjacent to a large vessel are
prevented from adequate heating due to flowing blood carrying away the heat) as
occurs with RFA, HIFU or microwave. In addition, IRE has demonstrated the
potential for real-time monitoring with ultrasonography (US).
With these distinctive characteristics, IRE has the potential to become a
successful alternative ablatoin method for solid tumors, especially in areas
around large blood-vessels and vulnerable structures such as bile ducts,
ureters or nerves.
Study objective
The primary objective of this study is to evaluate the safety in terms of
complication rate of IRE in the treatment of colorectal liver metastasis/es
<3,5 cm in patients undergoing surgical resection (metastatectomy, segmental
liver resection or (extended) hemi-hepatectomy).
Study design
Single center pilot study
Intervention
Guideline indication for resectability of colorectal liver metastasis will be
judged in consensus by a multidisciplinary liver team. After study inclusion,
all patients will undergo a laparotomy according to the judgment of the
surgeon. After liver exposure the interventional radiologist will position the
probes under ultrasound guidance and will start ablation with the NanoKnife
according to protocol under careful ECG monitoring. After ablation, the surgeon
will proceed with the resection of the metastasis. Standard histological
examination of the specimen, with additional caspase-3 analysis will be
performed.
Study burden and risks
Participation in the study will not cause a significant additional burden for
the patient.
Participation in the study will probably not be associated with additional
risks for the patient. However, the goal of this study is to prove the safety
of IRE and therefore this needs to be confirmed by means of this study.
Preclinical as well as clinical studies show a favorable complication profile
in comparison to other local treatment modalities in the liver, due to the
non-thermal treatment effect. IRE carries a small risk of bleeding, fistula
formation or infection that is comparable to other procedures were needles are
inserted into the body, especially when 2 or 3 needles are used at once.
Additionally, due to the high voltage used with IRE, there is a small risk of
precipitating muscle contractions, bradycardia/hypotension and cardiac
arrhythmias. However, since the use of the Accusync ECG gating device, which
enables synchronized pulsing, no irregularities have been observed within the
registry (now including >1000 patients). Muscle contractions will be
prevented/treated with additional muscle relaxants during the procedure. Rare
complications of IRE additional to liver surgery are electric shock, myocardial
infarction, CVA and vagal stimulation .
Participation in the study will not lead to an individual benefit for the
patient, but participation might contribute to the development of better future
treatment strategies in solid tumors.
De Boelelaan 1117
Amsterdam 1081 HZ
NL
De Boelelaan 1117
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
Screening must be performed no longer than 4 weeks prior to study inclusion. Subjects are eligible if they meet the following criteria:
* Histological or cytological documentation of primary colorectal tumor
* Liver metastases visible on FDG PET-CT or contrast-enhanced CT, size * 3,5 cm.
* Resectability (re)confirmed by intraoperative US
* Age 18 years or older
* WHO performance status 0 * 2
* Life expectancy of at least 12 weeks
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion:
Hemoglobin * 5.6 mmol/L; Absolute neutrophil count (ANC) * 1,500/mm3; Platelet count * 100*109/l; Total bilirubin * 1.5 times the upper limit of normal (ULN); ALT and AST * 2.5 x ULN; Serum creatinine * 1.5 x ULN or a calculated creatinine clearance ³ 50 ml/min; Prothrombin time or INR < 1.5 x ULN;
Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician).
* Written informed consent.
Exclusion criteria
Subjects who meet the following criteria at the time of screening will be excluded:
* Lesion > 3,5 cm
* History of cardiac disease:
- Congestive heart failure >NYHA class 2;
- Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
- Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers are permitted)
* History of epilepsy
* Uncontrolled hypertension. Blood pressure must be *160/95 mmHg at the time of screening without medication or on a stable antihypertensive regimen.
* Uncontrolled infections (> grade 2 NCI-CTC version 3.0).
* Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment.
* Immunotherapy * 6 weeks prior to the procedure
* Chemotherapy within 12 weeks before surgery
* Radiotherapy, RFA or MWT treatment of target lesions prior to resection
* Concomitant use of dexamethasone, anti-convulsants and anti-arrhythmic drugs.
* Severe allergy for contrast media not controlled with premedication.
* Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL41089.029.12 |