Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer, Pancreatic Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/5/2018 |
| Start Date: | May 15, 2018 |
| End Date: | May 2023 |
| Contact: | Sung Kwon, MD |
| Email: | steve-kwonmd@mail.holyname.org |
| Phone: | 201-541-5989 |
Patients with pancreatic ductal adenocarcinoma will be screened by pancreatic protocol
cross-sectional imaging to see if they have locally advanced unresectable pancreatic ductal
adenocarcinoma. Patients with unresectable disease will undergo at least four cycles of
standard of care chemotherapy before being re-evaluated for treatment with irreversibe
electroporation (i.e., Nanoknife). If patients are over 18 years of age, have pancreatic
tumor size less than 5cm, and can safely undergo a laparotomy, they will be considered for
participation. The patient cannot undergo the procedure if they have metastatic disease, a
pacemaker or an electrostimulator, a metallic stent that cannot be exchanged, a convulsive
(i.e., epilepsy) condition, an estimated survival less than three months, atrial fibrillation
with an undetectable waveform on ECG sync device, severe cardiac disease, a international
normalised ratio (INR) that is less than 1.5, or a performance status >2.
For the procedure, a laparotomy will be performed and Nanoknife probe placement will be done
under intraoperative ultrasound. The number of probes, depth of the probes and rapid pulse
series will be decided by the surgeon and are based on the size and location of the desired
area of ablation.
Patients will be followed for overall survival, progression-free survival, tumor response,
tumor markers, symptom improvement, and complications. Symptom improvement will be measured
by assessment of pain, quality of life, total bilirubin if biliary obstruction is initially
present, and oral intake if gastric outlet obstruction is initially present. They will have
regular follow up with the surgeon that will include routine surveillance imaging and blood
work.
cross-sectional imaging to see if they have locally advanced unresectable pancreatic ductal
adenocarcinoma. Patients with unresectable disease will undergo at least four cycles of
standard of care chemotherapy before being re-evaluated for treatment with irreversibe
electroporation (i.e., Nanoknife). If patients are over 18 years of age, have pancreatic
tumor size less than 5cm, and can safely undergo a laparotomy, they will be considered for
participation. The patient cannot undergo the procedure if they have metastatic disease, a
pacemaker or an electrostimulator, a metallic stent that cannot be exchanged, a convulsive
(i.e., epilepsy) condition, an estimated survival less than three months, atrial fibrillation
with an undetectable waveform on ECG sync device, severe cardiac disease, a international
normalised ratio (INR) that is less than 1.5, or a performance status >2.
For the procedure, a laparotomy will be performed and Nanoknife probe placement will be done
under intraoperative ultrasound. The number of probes, depth of the probes and rapid pulse
series will be decided by the surgeon and are based on the size and location of the desired
area of ablation.
Patients will be followed for overall survival, progression-free survival, tumor response,
tumor markers, symptom improvement, and complications. Symptom improvement will be measured
by assessment of pain, quality of life, total bilirubin if biliary obstruction is initially
present, and oral intake if gastric outlet obstruction is initially present. They will have
regular follow up with the surgeon that will include routine surveillance imaging and blood
work.
Pancreatic ductal adenocarcinoma is extremely aggressive and is the 4th most frequent
tumor-related cause of death in the Western world. The one-year survival rate is 20 percent
and the 5-year overall survival rate is only 5 percent. Pancreatic ductal adenocarcinoma
often become symptomatic at very advanced stages with only 15 to 20 percent of patients being
able to undergo a therapeutic local resection. Patients who do not meet the criteria for
local consolidative resection may either have advanced locoregional disease and/or distant
metastases. Advanced locoregional pancreatic ductal adenocarcinoma without metastatic disease
has a survival rate of 6 to 12 months. Those with distant metastases have a survival rate of
only 3 to 6 months.
Locally advanced pancreatic adenocarcinoma is defined by the involvement of the superior
mesenteric artery, the celiac axis, and/or long segment portal vein occlusion on
cross-sectional imaging. Resectable tumors will be free from the superior mesenteric vein,
superior mesenteric artery and celiac axis, with no nodal involvement outside of the area of
resection. Unresectable disease will have occlusion, thrombosis or encasement that extends
for several centimeters of superior mesenteric vein and portal vein. Tumor abutment,
encasement or thrombosis of the superior mesenteric artery is also considered unresectable
disease. Involvement of lymph nodes outside of the area of resection also indicates that the
patient is not resectable.
For patients who have unresectable pancreatic ductal adenocarcinoma, chemotherapy and
radiation can only provide short-term disease control. Chemotherapy and radiation regimens
have not been shown to prolong survival significantly in this disease, and therefore, there
is a need for additional adjunctive or consolidative treatment to provide improved local
control, pain relief and possibly impact survival. Image guided ablation technique like
irreversible electroporation has shown promise as a new treatment option for patients with
stage III locally advanced pancreatic cancer.
A unique advantage of Nanoknife is that it does not require heat to ablate tumor cells,
rather it works by using high voltage but low energy direct current. The process in which low
energy direct current ablates tissue is called irreversible electroporation. In order to
understand how this process works, the investigators have to understand some background cell
biology. The cell membrane separates the intracellular space and the extracellular
space/fluid, and controls transport processes between the two compartments of the cell.
Electroporation increases cell membrane permeability by subjecting it to an electrical field
and uses rapid series of short electrical pulses delivered using high voltage but low energy
direct current to create defects (pores) in the cell membrane that result in loss of
homeostasis and cell death. The result is a well demarcated area of ablation. The Nanoknife
system comes with 19 gauge needles that have depth markings. The needle surface is echogenic.
The active electrode length is adjustable in 0.5 cm increments from zero to 4 cm. There is an
external electrocardiogram synchronization device that automatically detects the R wave and
energy is delivered synchronously to the R wave. The electrodes can be arranged in multiple
configurations using two to six electrodes. The spacing between the electrodes can be from
0.5 cm to 2.0 cm, and electrode exposure can be from 0.5 cm to 4.0 cm. Energy is delivered
between the electrode pairs, and this results in an area of ablated tissue.
Nanoknife is particularly useful in patients with pancreatic ductal adenocarcinoma because of
the proximity of pancreatic tumors to critical surrounding structures such as bile ducts and
major blood vessels. Because it does not use heat to ablate tissue (which induces necrosis)
but rather uses cell apoptosis, it theoretically has no impact on the surrounding structures
that mainly consist of proteins like vascular elastic and collagenous structures as well as
peri-cellular matrix proteins (protecting large blood vessels and bile ducts). Further study
of Nanoknife is needed to see if this therapy can potentially impact survival and/or provide
adequate local palliation to improve quality of life in patients with locally advanced
unresectable pancreatic ductal adenocarcinoma.
tumor-related cause of death in the Western world. The one-year survival rate is 20 percent
and the 5-year overall survival rate is only 5 percent. Pancreatic ductal adenocarcinoma
often become symptomatic at very advanced stages with only 15 to 20 percent of patients being
able to undergo a therapeutic local resection. Patients who do not meet the criteria for
local consolidative resection may either have advanced locoregional disease and/or distant
metastases. Advanced locoregional pancreatic ductal adenocarcinoma without metastatic disease
has a survival rate of 6 to 12 months. Those with distant metastases have a survival rate of
only 3 to 6 months.
Locally advanced pancreatic adenocarcinoma is defined by the involvement of the superior
mesenteric artery, the celiac axis, and/or long segment portal vein occlusion on
cross-sectional imaging. Resectable tumors will be free from the superior mesenteric vein,
superior mesenteric artery and celiac axis, with no nodal involvement outside of the area of
resection. Unresectable disease will have occlusion, thrombosis or encasement that extends
for several centimeters of superior mesenteric vein and portal vein. Tumor abutment,
encasement or thrombosis of the superior mesenteric artery is also considered unresectable
disease. Involvement of lymph nodes outside of the area of resection also indicates that the
patient is not resectable.
For patients who have unresectable pancreatic ductal adenocarcinoma, chemotherapy and
radiation can only provide short-term disease control. Chemotherapy and radiation regimens
have not been shown to prolong survival significantly in this disease, and therefore, there
is a need for additional adjunctive or consolidative treatment to provide improved local
control, pain relief and possibly impact survival. Image guided ablation technique like
irreversible electroporation has shown promise as a new treatment option for patients with
stage III locally advanced pancreatic cancer.
A unique advantage of Nanoknife is that it does not require heat to ablate tumor cells,
rather it works by using high voltage but low energy direct current. The process in which low
energy direct current ablates tissue is called irreversible electroporation. In order to
understand how this process works, the investigators have to understand some background cell
biology. The cell membrane separates the intracellular space and the extracellular
space/fluid, and controls transport processes between the two compartments of the cell.
Electroporation increases cell membrane permeability by subjecting it to an electrical field
and uses rapid series of short electrical pulses delivered using high voltage but low energy
direct current to create defects (pores) in the cell membrane that result in loss of
homeostasis and cell death. The result is a well demarcated area of ablation. The Nanoknife
system comes with 19 gauge needles that have depth markings. The needle surface is echogenic.
The active electrode length is adjustable in 0.5 cm increments from zero to 4 cm. There is an
external electrocardiogram synchronization device that automatically detects the R wave and
energy is delivered synchronously to the R wave. The electrodes can be arranged in multiple
configurations using two to six electrodes. The spacing between the electrodes can be from
0.5 cm to 2.0 cm, and electrode exposure can be from 0.5 cm to 4.0 cm. Energy is delivered
between the electrode pairs, and this results in an area of ablated tissue.
Nanoknife is particularly useful in patients with pancreatic ductal adenocarcinoma because of
the proximity of pancreatic tumors to critical surrounding structures such as bile ducts and
major blood vessels. Because it does not use heat to ablate tissue (which induces necrosis)
but rather uses cell apoptosis, it theoretically has no impact on the surrounding structures
that mainly consist of proteins like vascular elastic and collagenous structures as well as
peri-cellular matrix proteins (protecting large blood vessels and bile ducts). Further study
of Nanoknife is needed to see if this therapy can potentially impact survival and/or provide
adequate local palliation to improve quality of life in patients with locally advanced
unresectable pancreatic ductal adenocarcinoma.
Inclusion Criteria:
- age >18
- locally advanced unresectable pancreatic ductal adenocarcinoma as demonstrated by CT
or MRI
- must have received standard chemotherapy and completed at least four cycles of
treatment at least 5 weeks prior to therapy with Nanoknife
- INR <1.5
- able to tolerate laparotomy (medical/cardiac clearance as needed)
- able to comply with protocol requirements
- women of childbearing potential must have a negative serum pregnancy test and be
practicing an effective form of birth control
Exclusion Criteria:
- patients with tumor >5cm after completion of chemotherapy
- presence of metastatic disease
- patients with a pacemaker or electrostimulator
- estimated survival is less than 3 months
- presence of a metallic stent (biliary or duodenal) which cannot be removed or
exchanged for plastic
- ECOG performance status more than or equal to 2
- epilepsy or other convulsive conditions
- cannot tolerate general anesthesia
- patients with atrial fibrillation who have an undetectable wave form on the ECG
synchronization device
- patients with inducible ischemia on cardiac stress test or uncontrolled angina
- white blood cell count less than or equal to 2,000, absolute neutrophil count <1,000,
platelets <50,000
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