|- candidate number||15028|
|- NTR Number||NTR4049|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||23-jun-2013|
|- Secondary IDs||NL45048.058.13 ABR|
|- Public Title||Irreversible Electroporation for treatment of unresectable, locally advanced pancreatic cancer in the
Leiden University Medical Center:
a phase I/II study
|- Scientific Title||Irreversible Electroporation for treatment of unresectable, locally advanced pancreatic cancer in the
Leiden University Medical Center:
a phase I/II study
|- ACRONYM||IRE-pancreas LUMC|
|- hypothesis||Using Irreversible Electroporation on locally advanced pancreatic adenocarcinoma deemed unresectable during explorative laparotomy, will increase progression free survival and median overall survival.|
|- Healt Condition(s) or Problem(s) studied||Locally advanced unresectable pancreatic cancer|
|- Inclusion criteria||1. 18 years of age;|
2. Tumour in the pancreas suspected for adenocarcinoma;
3. Based on preoperative imaging the tumor is judged as resectable in the multidisciplinary meeting, but is also shown to have at least abutment of venous vascular structures (portal vein, superior mesenteric vein) (see table 1 in Appendix A);
4. Tumour size must be < 4 cm at the time of IRE treatment and must be measurable;
5. Karnofsky Performance Status score of > 80% or ECOG of 0 to 1;
6. INR < 1.3;
7. ANC > 1.5x109/L;
8. Bilirubin level <250mmol/L otherwise drainage is performed and surgery is posponed until bilirubin levels have returned to normal;
9. Willing and able to comply with the protocol requirements;
10. Able to comprehend and have signed an Informed Consent Form (ICF) to participate in the study.
Inclusion criteria: per-operative inclusion criteria
1. Unresectable during intraoperative ultra sound investigation after minimal surgical exploration:
a. Extensive tumour growth around superior mesenteric vein and their side-branches (see table 2 in Appendix A).
b. Involvement of arterial structures
c. Per-operative diagnosis confirmed by frozen section analysis
|- Exclusion criteria||1. Contraindications for laparotomy or IRE|
2. Resectable at laparotomy
3. Evidence of distant metastases (pre or per-operative)
4. Screening creatinine reported as > 2.3 mg/dL
5. Inability to stop anticoagulant therapy for 7 days prior to and 7 days post treatment with the NanoKnife System
6. Known history of contrast allergy that cannot be medically managed
7. Women who are pregnant or currently breast feeding
8. Women of child bearing potential who are not willing to use hormonal contraception or intrauterine device (IUD) during the study
9. Have a cardiac pacemaker or defibrillator
10. Have metal parts in the vicinity of lesions to be ablated at the time of treatment with the NanoKnife System
11. Recent history of myocardial infarction (within the past 3 months)
12. Patients with a history of Epilepsy
13. Patients with a current history of clinically significant Cardiac Arrhythmia.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-sep-2013|
|- planned closingdate||1-okt-2014|
|- Target number of participants||15|
|- Interventions||Irreversible electroporation (IRE) is a new ablation technique. By changing the electric potential across the cell membrane, the lipid bilayer is disrupted and becomes porous. With high voltages, applied for milliseconds in multiple repetitive cycles, this process is irreversible leading through apoptosis to cell death. IRE is already effective at settings before extensive heat is produced. Therefore it is defined as a non-thermal ablation technique without unwanted effects like heatsink and direct thermal damage.
IRE has been shown to spare connective tissue architecture, leaving bile ducts, vessels and other vital structures patent. This will allow ablations of tumors with close relation to these vital structures.
In this study we want to investigate the safety and feasibilty of this procedure, by looking at the survival, quality of life after the procedure, and the effect on the tumor. Also this study investigates the feasibilty for the radiologist/surgeon in the operating room. |
|- Primary outcome||Safety and feasibility of the procedure. The safety is checked by reporting adverse events, also the first 5 procedures will be filmed. The feasibility is measured by evaluating specific questions about procedure and technical aspects. This is evaluated after every procedure. |
|- Secondary outcome||- Local progression free survival, based on CT scans. Once pre-procedural, than 5days after, 3,6,9,12,18,24 months after the procedure. |
- Overall survival in days - day of surgery untill day of death
- Tumour downstaging/follow-up of local situation, based on repeated CT scans
- NRS pain score; this will be measured daily post-operative. Outcomes will be compared with a control group of patients treated before this trial.
- Hospital stay (days: form day of procedure till day of discharge)
- Tumour response related to immune defence (blood samples). Once pre-procedural, than 5days after, 3,6,9,12,18,24 months after the procedure.
- Quality of life; as measured by EORTC questionnaire. Once pre-procedural, than 3,9, 18 months after the procedure.
|- Timepoints||The safety endpoints will be evaluated at the moment an adverse event occurs. Feasibility is evaluated after every procedure. |
Patients will be seen daily postoperative untill discharge, also the NRS score is asked for daily. Before discharge/5 days post-operative a CT scan will be performed; from then on every 3 months.
Blood samples are taken on the same days as the CT scans. The QOL questionnaire is filled in once before the procedure and than 3, 9 and 18 months after the procedure.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| E.M. de Leede|
|- CONTACT for SCIENTIFIC QUERIES|| E.M. de Leede|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Irreversible electroporation is a new technique for local ablation of soft tissue. It applies high voltages for milliseconds in multiple repetitive cycles to create pores in cell membranes. This process is irreversible leading to cell death through apoptosis. Since IRE does not use heat for cell destruction as other local ablative techniques do, connective tissue architecture is not damaged, leaving nearby vital structures like blood vessels and bile ducts patent. Also heatsink is not a problem. These characteristics makes IRE a promising tool for treating pancreatic cancer. Radical surgical treatment of pancreatic cancer is frequently difficult due to its presence in proximity of large vessels.
In the Netherlands the treatment of non-metastatic, locally advanced pancreatic cancer as shown on pre-operative imaging is limited to explorative laparotomy. In a fair number of these explorations surgical resection cannot be achieved. Then, only a gastro-enteral and biliary bypass is provided leaving the primary pancreatic tumor untouched.|
At present small case series have been published on open and percutaneous IRE on highly selected pancreatic cancer patients. The results described are promising and show proof of principle for IRE as a local ablative tumor therapy. Although in the literature IRE seems to be safe, formal phase I/II studies showing safety and feasibility have not been performed.
This protocol describes a phase I/II study of IRE applied to locally advanced pancreatic cancer deemed resectable on pre-operative imaging, but shown to be unresectable during explorative laparotomy.
|- Main changes (audit trail)|
|- RECORD||23-jun-2013 - 10-jul-2013|