Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Colorectal Liver Metastases - "Ablate and Resect"
18 Years
N/A
Both
Colorectal Liver Metastases, Metastatic Liver Disease
Trial Information
Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Colorectal Liver Metastases - "Ablate and Resect"
This pilot-study is designed to determine the safety of IRE using the NanoKnife on
colorectal liver metastases. Secondary, feasibility, histological effect on the ablated
cells and exact shape and size of the ablated area will be determined.
Study design:
Patients with resectable CRLM (1 lesion or more) undergoing surgical resection of the
metastases will receive study information to participate in this pilot-study. Limited
extrahepatic disease is not contra-indicated.
Patients will undergo a general pre-procedural work-up: total body FDG PET-CT, ceCT of the
abdomen, anesthetic review with special attention to cardiac history, baseline full blood
examination, urea and electrolytes, renal function tests, liver enzymes and coagulation
profile test.
The procedure is conducted under general anaesthesia with muscle relaxants to prevent
patient motion and epidural analgesia. A laparotomy will be performed at the surgeon's
discretion for optimal liver exposure. Intraoperative ultrasonography (IOUS) will be carried
out by an experienced interventional radiologist for exact evaluation of maximum diameter,
number and location of all lesions and to confirm resectability (if lesions prove not to be
resectable, only RFA will be performed according to standard of care). All lesions will be
biopsied. The electrodes will be placed under ultrasound guidance according to
manufacturer's guidelines in the lesions that are eligible for resection. After correct
placement of the electrodes the lesions will be ablated according to protocol with ECG
synchronization and the ablation zone is determined by US.
During the procedure the cardiac rhythm will be closely monitored and a defibrillator will
be present at all times.
After IOUS confirmation of complete ablation (at least 30 minutes after ablation of the
lesion) the surgeon will perform a partial liver resection / metastasectomy including the
ablated lesions and the surgical procedure is ended as usual. After the treatment of all
lesions with the NanoKnife and before resection (and RFA of unresectable CRLM if indicated),
blood samples will be drawn to determine renal function and liver enzymes since cell
destruction may cause biochemical abnormalities.
The resected specimen will be transported to the department of pathology. After sectioning,
the specimen will be photographed extensively to determine exact shape and size of the
ablated area. One slice is stained in vitality-staining (TTC), to macroscopically
distinguish viable from nonviable tissue.
After formalin fixation, the specimen is stained and examined under light microscopy
according to standard protocol to determine radicality of the resection margins.
Additionally, special attention will be given to indications for cellular damage, vessel
wall damage and size and shape of the ablation zone. Caspase-3 and BAX/BCL-2 analysis will
be performed to investigate the induction of apoptosis. The results will be compared to the
result of the biopsy taken prior to ablation.
On day one and day three post-operatively regular blood samples will be drawn, including
liver enzymes and renal function tests. After discharge, out of hospital follow-up will be
according to liver surgery protocol. The investigators aim to include 10 patients in this
pilot study.
Monitoring:
An independent monitor (quality officer) will monitor all study data according to Good
Clinical Practice (GCP). The informed consent of selected individual participants will be
checked. Source Data verification will be performed during onsite monitoring (to verify if
all data on the Case Report Form are in accordance with the source data). The intensity of
this verification is in relation to the risk associated with the intervention investigated.
Data that by all means will be checked are the informed consent form, in- and exclusion
criteria and the primary outcome. The monitor will also verify if all (S)AE's and SUSAR's
are reported adequately and within the time that is determined by legal rules and
regulations.
Inclusion Criteria:
- Histological or cytological documentation of primary colorectal tumor
- Liver metastases visible on FDG PET-CT or ceCT, size ≤ 3,5 cm and eligible for
resection
- Resectability re-confirmed per-operatively by US
- Age > 18 years
- 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:
- Lesion > 3,5 cm size
- History of epilepsy
- 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).
- Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of
screening on a stable antihypertensive regimen.
- Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use
of anticoagulants, ascites)
- 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 ≤ 12 weeks prior to the procedure
- Radiotherapy, RFA or MWA treatment of target lesions prior to resection
- Concomitant use of anti-convulsive and anti-arrhythmic drugs other than beta
blockers.
- Allergy to contrast media
- Any implanted stimulation device
- Any condition that is unstable or that could jeopardize the safety of the subject and
their compliance in the study.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome Description:
Safety using Common terminology Criteria for Adverse Events (CTCAE). Since the ablated tissue will be resected we expect procedure-related complications to occur mainly during the procedure.
Outcome Time Frame:
participants will be followed for the duration of hospital stay, an expected average of 1 week
Safety Issue:
Yes
Principal Investigator
Martijn R Meijerink, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
VU University Medical Center
Authority:
United States: Food and Drug Administration
Study ID:
NL 41089.029.12 COLDFIRE
NCT ID:
NCT01799044
Start Date:
November 2012
Completion Date:
July 2013
Related Keywords:
- Colorectal Liver Metastases
- Metastatic Liver Disease
- Irreversible electroporation
- IRE
- Electroporation
- Colorectal liver metastases
- CRLM
- Safety
- Feasibility
- Efficacy
- Single-center
- Low Energy Direct Current
- Ablate-and-resect
- Nonthermal ablation
- Ablation
- Liver Diseases
- Neoplasm Metastasis
- Neoplasms, Second Primary
- Liver Neoplasms
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