Pancreatic CancerNCT03614910
Ablation of Unresectable Locally Advanced Pancreatic Cancer With Irreversible Electroporation (IRE) System
An observational study of Pancreatic Cancer, run by Holy Name Medical Center, Inc. at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Nanoknife Irreversible Electroporation
- Type of treatment
- Medical device
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2018to 1 May 2021
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with locally advanced unresectable pancreatic cancer who meet the criteria for Nanoknife and are able to safely undergo a laparotomy.
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability
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.
Read the detailed description
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.
- Conditions
- Pancreatic Cancer
- Being tested
- Nanoknife Irreversible Electroporation
- Keywords
- Locally advanced pancreatic cancer, irreversible electroporation, Nanoknife
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nanoknife Irreversible ElectroporationDevice
Irreversible electroporation will be delivered between electrodes that are placed by intraoperative ultrasound guidance around the tumor
| Study group | Role | What they receive |
|---|---|---|
| Locally Advanced Pancreatic Cancer | Patients with locally advanced unresectable pancreatic cancer. Unresectable tumors as defined by:
* occlusion, thrombosis or several centimeters of encasement of the superior mesenteric vein or portal vein
* tumor abutment greater than 180 degrees of the superior mesenteric artery or thrombosis of the artery
* abutment or encasement of the celiac axis
* involvement of lymph nodes outside the area of resection Receives: Device: Nanoknife Irreversible Electroporation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Time from Nanoknife treatment to the patient's death
Measured: up to 10 years
Local progression-free survival
Time from Nanoknife treatment to local disease progression
Measured: up to 10 years
Distant disease-free survival
Time from Nanoknife treatment until distant disease development
Measured: up to 10 years
Tumor response
Change in tumor size in response to Nanoknife treatment using RECIST criteria V1.1 (CR, PR, SD, PD)
Measured: First year
Secondary outcomes (5)
Complications
The incidence of the following complications after treatment with Nanoknife will be recorded: hematologic, ileus, bile leak, portal vein thrombosis, deep vein thrombosis, pulmonary, renal failure, ascites, wound infection, dehydration/failure to thrive/nausea, bleeding, diarrhea, duodenal leak, liver insufficiency, pancreatic leak
Measured: 90 days
Tumor Markers
CA 19-9 will be measured at 6 weeks post op, 3 months post op, 6 months post op, 1 year post op, then yearly
Measured: up to 10 years
Biliary Obstruction
Change in biliary obstruction after treatment will be recorded using total bilirubin and conjugated/unconjugated bilirubin levels at each follow up office visit
Measured: up to 10 years
Gastric outlet obstruction
Gastric outlet obstruction after treatment will be monitored with symptoms resulting in decreased oral intake (nausea, vomiting, and inability to eat). Objectively we will also measure patient weight in kilograms at each office visit.
Measured: up to 10 years
Cancer related pain
Cancer related pain after treatment will be measured using Visual Analog Pain scale 0-10, zero being no pain and 10 being worst pain possible. Pain scale will be assessed at each follow up visit.
Measured: up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start15 May 2018
- Primary completion1 May 2021
- Study completion1 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- Holy Name Medical Center, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sung Kwon, MD, Principal investigator, Holy Name Medical center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03614910
- Sponsor's protocol ID
- holynamenanoknife1
- Status last verified
- Aug 2022
- First submitted
- 12 Jul 2018
- Last updated
- 3 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability
- ClinicalTrials.gov ID
- NCT03614910
- Acronym / sponsor ID
- holynamenanoknife1
- Conditions
- Pancreatic Cancer
- Keywords
- Locally advanced pancreatic cancer, irreversible electroporation, Nanoknife
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Holy Name Medical Center, Inc.University, hospital or other
- Study start
- 15 May 2018 (actual)
- Primary completion
- 1 May 2021 (actual)
- Study completion
- 1 May 2021 (actual)
- First posted
- 3 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Locally Advanced Pancreatic Cancer | – | Device: Nanoknife Irreversible ElectroporationPatients with locally advanced unresectable pancreatic cancer. Unresectable tumors as defined by: * occlusion, thrombosis or several centimeters of encasement of the superior mesenteric vein or portal vein * tumor abutment greater than 180 degrees of the superior mesenteric artery or thrombosis of the artery * abutment or encasement of the celiac axis * involvement of lymph nodes outside the area of resection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with locally advanced unresectable pancreatic cancer who meet the criteria for Nanoknife and are able to safely undergo a laparotomy.
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nanoknife Irreversible ElectroporationIrreversible electroporation will be delivered between electrodes that are placed by intraoperative ultrasound guidance around the tumor | Device | Locally Advanced Pancreatic Cancer |
Primary outcome
Overall survival
Time frame: up to 10 years
Time from Nanoknife treatment to the patient's death
Local progression-free survival
Time frame: up to 10 years
Time from Nanoknife treatment to local disease progression
Distant disease-free survival
Time frame: up to 10 years
Time from Nanoknife treatment until distant disease development
Tumor response
Time frame: First year
Change in tumor size in response to Nanoknife treatment using RECIST criteria V1.1 (CR, PR, SD, PD)
5 secondary outcomes
Complications
Time frame: 90 days
Tumor Markers
Time frame: up to 10 years
Biliary Obstruction
Time frame: up to 10 years
Gastric outlet obstruction
Time frame: up to 10 years
Cancer related pain
Time frame: up to 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sung Kwon, MD principal investigator
Holy Name Medical center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pancreatic Cancer, run by Holy Name Medical Center, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: up to 10 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2022.