None listed
Conditions
Brief summary
The aim of this study is to investigate whether addition of a new therapy using the NanoKnife system improves survival in patients with unresectable stage 3 pancreatic cancer. The Nanoknife system is a type of irreversible electroporation (IRE) device. “Electroporation” is a cellular destruction technology that can be used to treat cancer. It uses electrical pulses to make small holes in cells that cause cell death. This destroys the targeted tissue in the body and the treated tissue is then removed by the body’s natural processes in a matter of weeks, mimicking natural cell death. Who is it for? You may be eligible for this study if you are aged 18 years or older, have a diagnosis of unresectable stage 3 pancreatic ductal adenocarcinoma, and have received (or will receive) at least 3 months of a single line of chemotherapy prior to enrolment. Study details Within 1 to 3 weeks after completing their 3 months of chemotherapy, all participants will undergo the IRE procedure. The IRE procedure will only be performed by a surgeon qualified in the use of the NanoKnife System. The procedure will require a general anaesthetic and will take approximately 2-3 hours to complete. As part of the procedure, a diagnostic laparoscopy (a procedure where a camera is inserted into the abdomen through small incisions) will be used to rule out the presence of metastases. Following this, the abdomen will be opened to perform IRE. A tissue biopsy will be taken during the procedure if safe to do so. After recovery from anaesthesia, participants will stay in hospital for up to 7 days before being discharged home when they are well. Participants will be asked to complete a number of questionnaires at 3, 6, 12, 18, and 24 months following the procedure, and will also be asked to report any side-effects that they experience for the duration of follow-up. Following treatment with the NanoKnife, you may continue to receive other standard of care treatment such as further chemotherapy or radiotherapy. This will be decided by your treating oncologist. It is hoped that this study may demonstrate that use of the NanoKnife system in patients with unresectable stage 3 pancreatic cancer who have already received chemotherapy is safe to use, improves survival, reduces pain, and increases quality of life compared to patients receiving chemotherapy alone.
Interventions
This is an open-label, prospective, multi-centre registry-based study evaluating the use of Irreversible Electroporation (IRE) with the NanoKnife system in unresectable stage 3 pancreatic cancer. Irreversible electroporation (IRE) is a technique using non-thermal energy to create permanent nanopores in the cell membrane in order to disrupt cellular homeostasis. After delivering a sufficient number of high voltage pulses, the cells within the electrical field will be irreversibly damaged. These
This is an open-label, prospective, multi-centre registry-based study evaluating the use of Irreversible Electroporation (IRE) with the NanoKnife system in unresectable stage 3 pancreatic cancer. Irreversible electroporation (IRE) is a technique using non-thermal energy to create permanent nanopores in the cell membrane in order to disrupt cellular homeostasis. After delivering a sufficient number of high voltage pulses, the cells within the electrical field will be irreversibly damaged. These damaged cells die by apoptosis and are removed by the body’s own lymphatic system. Stage 3 pancreatic cancer patients must have received 3 months of FOLFIRINOX or gemcitabine-based chemotherapy for unresectable stage 3 pancreatic cancer prior to enrolment. These two chemotherapy regimens reflect current clinical practice and guideline recommendations. The study investigator will evaluate the risk to each participant on an individual basis and discuss the risks and benefits of study participation with the participant/legal representative. While the benefits of the NanoKnife procedure in pancreatic cancer have not been well characterised and doing so is the purpose of this trial, anecdotal reports of use in unresectable pancreatic carcinoma suggest that the procedure may improve survival and ameliorate pain due to the disease. Results from the use of IRE in prostate carcinoma support a low complication rate. All study participants will undergo IRE with the NanoKnife System, and the IRE procedure should be undertaken 1 to 3 weeks from the completion of 3 months of chemotherapy. Only a surgeon qualified in the use of the NanoKnife System will perform the IRE, and the duration of the IRE procedure is approximately 2-3 hours. Information related to the NanoKnife device specifications, IRE procedure, adjunctive procedures (if any were performed), anaesthesia/surgical observations and adverse events (if any were experienced) will be captured for every participant. In the setting of pancreatic cancer, due to the retroperitoneal position of the pancreas, irreversible electroporation by the NanoKnife System is undertaken using an open approach. A general anaesthetic will be required. A diagnostic laparoscopy is undertaken initially to rule out occult solid organ liver as well as peritoneal or mesenteric metastases. A midline abdominal lesion is then performed. Intra-operative ultrasound will be utilised to assess the tumour dimension and surrounding structures to determine the number and configuration of probes. Two to six probes (depending on the size and position of the tumour) will be inserted. Probe placement can be tracked with ultrasound throughout placement. Short, high voltage pulses are then delivered by the NanoKnife System. Involved lymph nodes may be treated if they are within the IRE field but probe placement is determined by the primary tumour and not the presence of involved nodes. The IRE procedure aims to treat the whole tumour and not just reduce the size of the tumour. The procedure will not include surgical resection (“debulking”) of the tumour. A tissue biopsy will be undertaken intra-operatively for exploratory/translational studies only if it is safe to do so. After recovery from anaesthesia, patients will remain hospitalised for up to 7 days and discharged home when they are well. Participants will be follow-up for a minimum period of 24 months post-IRE. Following treatment with the NanoKnife system, any systemic chemotherapy should be administered as per standard institution guidelines. Dose modifications to chemotherapy in line with standard clinical care are acceptable at the treating oncologist’s discretion. Participants will be required to attend clinic visits for follow-up every 3 to 4 months for a minimum of 24 months after enrolment.
Sponsors
Walter & Eliza Hall Institute of Medical Research (WEHI)
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1 Patient has a diagnosis of unresectable Stage 3 pancreatic ductal adenocarcinoma cancer cytologically or pathologically confirmed as per American Joint Committee on Cancer (AJCC) staging criteria. 2 Patient is newly diagnosed and has only received a single line of therapy for at least 3 months prior to enrolment. They must have received either modified FOLFIRINOX or gemcitabine-based chemotherapy. 3 Patient has a tumour evaluated as Stage 3 according to National Comprehensive Cancer Network (NCCN) guidelines, based on radiographic imaging or exploratory surgery. 4 Maximum axial tumour dimension of less than or equal to 3.5cm, after receiving at least three months of treatment with a modified FOLFIRINOX or gemcitabine-based regimen. 5 Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6 Patient has an American Society of Anaesthesiologists (ASA) classification of physical health status of 1 or 2.
Exclusion criteria
1 Patients who at 3 months after induction chemotherapy have evidence of disease progression. 2 Patients who have undergone prior radiation therapy or surgical resection for treatment of pancreatic cancer. 3 Patients who have received IRE for margin accentuation. 4 Patients who are unable to tolerate general anaesthetic with full skeletal muscle blockade. 5 History of another primary cancer within the last 3 years, with the exception of non-melanomatous skin cancer and carcinoma in-situ. 6 Patients who are actively bleeding, anticoagulated, coagulopathy, or have any of the following haematology results: a. Haemoglobin <100 g/L without the support of growth factors or transfusion b. Absolute neutrophil count <1.5 x 109/L c. Platelet count <100 x 109/L 7 Patients with the presence of implanted cardiac pacemakers, defibrillators, electronic devices or implanted devices with metal parts in the thoracic cavity at the time of IRE. 8 Patients with history of epilepsy or other neurological disease. 9 Patients with inadequate organ function: a. Patients with Stage 3 (GFR 30 to 44ml/min), 4 (15 to 29ml/min), or 5 (<15ml/min) chronic kidney disease. b. Aspartate aminotransferase/alanine aminotransferase >2.5 x upper limit of normal. c. Clinically significant cardiovascular disease i.e. active or <12 months since e.g. cerebrovascular accident, myocardial infraction, unstable angina, New York Heart Association grade II or greater congestive heart failure, serious cardiac arrhythmias requiring medications, uncontrolled hypertension. 10 Patients who are pregnant or breastfeeding. Women of childbearing potential (WOCBP) must undergo pregnancy testing.
Outcome results
None listed