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Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability

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ClinicalTrials.gov Identifier: NCT03614910
Recruitment Status : Recruiting
First Posted : August 3, 2018
Last Update Posted : August 3, 2018
Sponsor:
Information provided by (Responsible Party):
Holy Name Medical Center, Inc.

Tracking Information
First Submitted Date July 12, 2018
First Posted Date August 3, 2018
Last Update Posted Date August 3, 2018
Actual Study Start Date May 15, 2018
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 30, 2018)
  • 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)
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: July 30, 2018)
  • Complications [ Time Frame: 90 days ]
    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
  • Quality of Life [ Time Frame: up to 10 years ]
    Treatment related quality of life changes will be measured using the WHOQOL-BREF assessment at each follow-up visit
  • Tumor Markers [ Time Frame: up to 10 years ]
    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
  • Biliary Obstruction [ Time Frame: up to 10 years ]
    Change in biliary obstruction after treatment will be recorded using total bilirubin and conjugated/unconjugated bilirubin levels at each follow up office visit
  • Gastric outlet obstruction [ Time Frame: up to 10 years ]
    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.
  • Cancer related pain [ Time Frame: up to 10 years ]
    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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability
Official Title Ablation of Unresectable Locally Advanced Pancreatic Cancer With Nanoknife Irreversible Electroporation (IRE) System: Response and Tolerability
Brief 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. 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 Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 10 Years
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with locally advanced unresectable pancreatic cancer who meet the criteria for Nanoknife and are able to safely undergo a laparotomy.
Condition Pancreatic Cancer
Intervention Device: Nanoknife Irreversible Electroporation
Irreversible electroporation will be delivered between electrodes that are placed by intraoperative ultrasound guidance around the tumor
Study Groups/Cohorts 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
Intervention: Device: Nanoknife Irreversible Electroporation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 30, 2018)
30
Original Estimated Enrollment Same as current
Estimated Study Completion Date May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Sung Kwon, MD 201-541-5989 steve-kwonmd@mail.holyname.org
Contact: Julie Schwegman, PAC 201-541-5989 schwegman@holyname.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03614910
Other Study ID Numbers holynamenanoknife1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Holy Name Medical Center, Inc.
Study Sponsor Holy Name Medical Center, Inc.
Collaborators Not Provided
Investigators Not Provided
PRS Account Holy Name Medical Center, Inc.
Verification Date July 2018