Chemotherapy Followed by Irreversible Electroporation in Patients With Unresectable Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This study is a single-arm clinical trial of irreversible electroporation (IRE) for the treatment of unresectable locally advanced pancreatic cancer (LAPC). The aim of the study is to evaluate the efficacy of IRE in this patient group. A statistical analysis of patient survival will be performed, comparing study participants to historical data from the Danish national database of pancreatic cancer patients.

Detailed Description
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Patients with unresectable LAPC can be included in the study. Prior to inclusion, initial treatment with chemotherapy with or without radiation therapy (RT) is administered to all patients accord to the referring institutions protocol. Some patients will have undergone an attempted resection prior to inclusion. It is expected, that a substantial number of patients are participants in the LAPC-03 protocol (FOLFIRINOX followed by local therapy (resection, RT and/or IRE) in patients with LAPC). After completion of initial therapy, potential study participants are restaged with a PET-CT scan and serum tumor markers. Patients found on restaging to be free of metastatic disease and without significant primary tumor progression will be candidates for IRE therapy. IRE therapy will be administered not earlier than 2 weeks after completion of initial therapy. IRE will be done under general anesthesia as an in-patient procedure. Patients will attend study specific visits with PET-CT scan 3, 6, 9, 12, 18 and 24 months post-IRE. Patients will attend the out-patient clinic after 1, 3, 6, 9, 12, 15, 18, 21 and 24 months. During this we will monitor pain, quality of life, global functioning and nutritional status. In patients who, at any time during the study, are assessed as candidates for resection, a more detailed re-evaluation of resectability is performed according to local preferences (e.g. EUS and/or LAP/LUS and/or CT and/or MR).

Official Title
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Chemotherapy Followed by Irreversible Electroporation in Patients With Unresectable Locally Advanced Pancreatic Cancer (CHEMOFIRE-2)

Conditions
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Unresectable Pancreatic Cancer

Intervention / Treatment
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* Procedure: IRE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytologically proven adenocarcinoma/carcinoma of the pancreas. Largest tumor diameter ≤4 cm in any plane. >18 years of age. Prior treatment with neoadjuvant chemotherapy for at least 2 months Tumor must be deemed as unresectable at the national pancreatic multidisciplinary team conference after neoadjuvant treatment. Non-progressive disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECiST 1.1) after neoadjuvant treatment. Patients must be able to give informed consent. Exclusion Criteria: Tumor is inaccessible e.g. due to venous dilation etc. (assessed with preoperative ultrasound). ASA score >3 ECOG performance status >2 Pregnancy. Atrial fibrillation. Implanted electronic device e.g. cardiac pacemakers or other electrostimulators. Metal stents or other metallic objects near the ablation zone (unless the stent can be replaced with a plastic stent prior to IRE). Signs of severe disease of the bone marrow, kidney or liver during time of treatment. Treatment may be postponed if the disease state is reversible. Severe allergies to anesthetic agent, paralytic agent or any of the equipment used during treatment. Patient is referred from hospital outside of Denmark

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients in the study will be compared to data from clinical registry.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br> | Procedure: IRE<br>* in situ irreversible electroporation<br>* Other names: irreversible electroporation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year survival proportion from 1) diagnosis and 2) IRE |  | 2 years after the last patient is enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival from 1) diagnosis and 2) IRE |  | 2 years after the last patient is enrolled | 
| Progression free survival after IRE |  | 2 years after the last patient is enrolled | 
| Median time to local progression after IRE |  | 2 years after the last patient is enrolled | 
| Median time to dissemination after IRE |  | 2 years after the last patient is enrolled | 
| 90-day complication rate and severity (Clavien-Dindo) |  | 90 days after the last patient is enrolled | 
| Resection rate |  | 2 years after the last patient is enrolled | 
| Quality of life (EORTC QLQ C-30) | Quality of life questionnaire - Core 30 is used to assess the quality of life in the included patients. Raw scores will be calculated according to the manual. Items will be grouped in: Global health status (range 0 - 100, high is good), Functional scales (range 0 - 100, high is good) and symptom scales (range 0 - 100 low is good). Differences in each scales during the course of the trial we be calculated seperately. | Every 3 months for 2 years after the intervention | 
| Perioperative pain perception (VAS) | Perioperative pain will be scores using the visual analogue pain scale (range 0 - 10, low score is less pain). | Every week for 1 month after the intervention | 
| Long term pain perception (m-BPI-SF) | Long term pain will be assessed using the modified Danish version of the Brief Pain Inventory - short form. The outcomes assessed will be an average score of pain severity items and interference items in accordance with the manual. The scales range from 0 to 10 (lower is less pain). | Every 3 months for 2 years after the intervention | 
| ECOG performance status | Physicians assessment of global functioning using the Eastern Cooperative Oncology Group perfomance status scale (range 0 - 5, low score is better) | Every 3 months for 2 years after the intervention | 
| Nutritional status assessment (PG-SGA-SF) | Nutritional status assessment using the Scored Patient-Generated Subjective Global Assessment (short form). The short form includes only patient reported measures and will be combined into a single score according to the manual (range 0 - 37,low score is better). | Every 3 months for 2 years after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advances pancreatic cancer, irreversible electroporation, nanoknife, phase II, efficacy