PANFIRE - Pilot-study: Irreversible Electroporation (IRE) to Treat Locally Advanced Pancreatic Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by VU University Medical Center
Sponsor:
Information provided by (Responsible Party):
Dr. M.R. Meijerink, VU University Medical Center
ClinicalTrials.gov Identifier:
NCT01939665
First received: September 3, 2013
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

Irreversible electroporation (IRE) is a new, minimal-invasive image-guided treatment method for tumors not amenable for surgical resection or thermal ablation, due to vicinity near vital structures such as vessels and bile ducts. With IRE, multiple electrical pulses are applied to tumorous tissue. These pulses alter the existing transmembrane potential of the cell membranes, and create 'nanopores', after which the cell dies through loss of homeastasis.

The purpose of this study is to investigate the safety of percutaneous IRE in the treatment of patients with locally advanced pancreatic carcinoma (LAPC). Other objectives are feasibility and efficacy of IRE based upon symptomatic response and tumor response.

Ten patients with histologically confirmed locally advanced pancreatic adenoacarcinoma (< 3.5cm) will undergo percutaneous irreversible electroporation of the tumor using CT and ultrasound guidance. After IRE, patients will be carefully monitored and any (serious) adverse events are registered. Follow-up will consist of frequent CT and MRI scanning, as well as serum CA19.9 tumor marker and quality of life questionnaires and pain registration forms.

We hypothesize that IRE in the pancreas will induce good symptom palliation and local tumor control, without causing severe complications.


Condition Intervention Phase
Locally Advanced Pancreatic Carcinoma (LAPC)
Non-metastasized Unresectable Pancreatic Carcinoma
Pancreatic Cancer
Device: NanoKnife "Irreversible electroporation (IRE)"
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PANFIRE - Pilot-study: Non-thermal Ablation Using Irreversible Electroporation (IRE) to Treat Locally Advanced Pancreatic Carcinoma - a Phase I Clinical Trial

Resource links provided by NLM:


Further study details as provided by VU University Medical Center:

Primary Outcome Measures:
  • Safety (number of adverse events) [ Time Frame: early: 90 days; late: 12 months ] [ Designated as safety issue: Yes ]
    Number of adverse events of IRE-treatment (within 12 months after treatment) are registered and analyzed according to the CTCAE version 4.0. Complications related to IRE are early complications during hospital admission (e.g. bile leak, bowel leak, infection, pancreatitis), or late complications of IRE such as bile duct stenosis that become apparent during follow-up in the year after treatment.


Secondary Outcome Measures:
  • Tumor response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • Ablation success: the ability to deliver the planned therapy and at 3 months to have no evidence of residual tumor;
    • Local recurrence rate (LRR): defined as the reappearance of viable tumor after a period of time during which viable tumor could not be detected;
    • Overall survival and (local and distant) progression-free survival.

  • Symptomatic response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • Quality of life using questionnaires;
    • Pain assessment and analgesics consumption;
    • General performance status of the patient.


Other Outcome Measures:
  • Immunologic response to IRE [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    IRE may aid in the generation of effective anti-tumor immunity. To examine the immunologic response before and after IRE, venous blood sampling will be performed 1 day before, 14 days after and 3 months after IRE. Employing five 25-mer peptides selected to cover the major HLA-A1, A2, -A3, and -A24 restricted T cell epitopes from mesothelin, peripheral blood mononuclear cells will be in vitro stimulated for 10 days, followed by a 24h restimulation and IFNγ Elispot read-out. Mesothelin-specific T cell frequencies will be determined at baseline, 14 days after IRE and after 3 months to assess memory responses.


Estimated Enrollment: 10
Study Start Date: September 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Irreversible electroporation
Single arm study: Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma
Device: NanoKnife "Irreversible electroporation (IRE)"
Tumor ablation with irreversible electroporation with the NanoKnife
Other Names:
  • IRE
  • NanoKnife

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Screening must be performed no longer than 2 weeks prior to study inclusion.

  • Radiologic confirmation of LAPC by at least ceCT of chest and abdomen (with the upper abdomen scanned according to a dedicated 3mm slice multiphase pancreatic tumor protocol), performed maximum 2 weeks prior to the procedure;
  • Maximum tumor diameter ≤ 5 cm;
  • Histological or cytological confirmation of pancreatic adenocarcinoma;
  • Age ≥ 18 years;
  • ASA-classification 0 - 3
  • Life expectancy of at least 12 weeks;
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to definite inclusion;

    • Hemoglobin ≥ 5.6 mmol/L;
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3;
    • Platelet count ≥ 100*109/l;
    • Total bilirubine ≤ 1.5 times the upper limit of normal (ULN);
    • ALT and AST ≤ 2.5 x ULN;
    • Serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 50 ml/min;
    • Prothrombin time or INR < 1.5 x ULN;
    • Activated partial thromboplastin time < 1.25 x ULN (therapeutic anticoagulation therapy is allowed if this treatment can be interrupted as judged by the treating physician);
  • Written informed consent;

Exclusion Criteria:

  • Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
  • Extrapancreatic metastases;
  • Successful downstaging after (radio)chemotherapy from previous unresectable/borderline tumor to resectable tumor;
  • Stage IV pancreatic carcinoma;
  • History of epilepsy;
  • History of cardiac disease:

    • Congestive heart failure >NYHA class 2;
    • Active Coronary Artery Disease (defined as myocardial infarction within 6 months prior to screening);
    • Cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted);
  • Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
  • Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites);
  • Uncontrolled infections (> grade 2 NCI-CTC version 3.0);
  • Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment;
  • Immunotherapy ≤ 6 weeks prior to the procedure;
  • Chemotherapy ≤ 6 weeks prior to the procedure;
  • Radiotherapy ≤ 6 weeks prior to the procedure;
  • Concomitant use of anti-convulsive and anti-arrhythmic drugs (other than beta blockers used for antihypertensive);
  • Allergy to contrast media;
  • Any implanted stimulation device;
  • Any implanted metal stent/device within the area of ablation that cannot be removed;
  • Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study;

Of note, patients with contra-indications for MRI will not be excluded from participation: in this case radiologic follow-up will consist of CT-scanning according to protocol.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01939665

Contacts
Contact: Hester J Scheffer, MD +31204445234 hj.scheffer@vumc.nl
Contact: Martijn R Meijerink, MD, PhD +31204444444 mr.meijerink@vumc.nl

Locations
Netherlands
VU University Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1081 HV
Contact: Hester J Scheffer, MD    +31204445234    hj.scheffer@vumc.nl   
Contact: Martijn R Meijerink, MD, PhD    +31204444444    mr.meijerink@vumc.nl   
Principal Investigator: Geert Kazemier, Prof. Dr.         
Principal Investigator: Martijn R Meijerink, MD, PhD         
Sponsors and Collaborators
VU University Medical Center
Investigators
Principal Investigator: Martijn R Meijerink, MD, PhD VU University Medical Center, Department of Radiology and Nuclear Medicine
Principal Investigator: Geert Kazemier, Prof. Dr. VU University Medical Center, Department of Surgery
Study Director: Cornelis van Kuijk, Prof. Dr. VU University Medical Center, Head of Department of Radiology,
  More Information

No publications provided

Responsible Party: Dr. M.R. Meijerink, Dr., VU University Medical Center
ClinicalTrials.gov Identifier: NCT01939665     History of Changes
Other Study ID Numbers: NL42888.029.13, 2013/155
Study First Received: September 3, 2013
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration
Europe: Conformité Européenne

Keywords provided by VU University Medical Center:
Locally advanced pancreatic carcinoma
LAPC
Irreversible electroporation
NanoKnife
IRE
Safety
Efficacy
Non-thermal ablation
Percutaneous ablation
Low Energy Direct Current

Additional relevant MeSH terms:
Pancreatic Neoplasms
Carcinoma
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 01, 2014