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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Unresectable Pancreatic Cancer
• Intervention / Treatment: Procedure: IRE

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rasmus Virenfeldt Flak, MD; Phone Number: +4597661181; Email: rasmus.virenfeldt@rn.dk
• Study Contact Backup: Name: Mogens Tornby Stender, Consultant Surgeon, PhD; Phone Number: +4597661761; Email: mogens.stender@rn.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Aalborg University Hospital
    • Contact: Rasmus Virenfeldt Flak, MD; Phone Number: +4597661181; Email: rasmus.virenfeldt@rn.dk
    • Contact: Mogens Tornby Stender, Consultant Surgeon, PhD; Phone Number: +4597661761; Email: mogens.stender@rn.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention	Procedure: IRE; in situ irreversible electroporation; Other Names: irreversible electroporation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Ole Thorlacius-Ussing, MD, DMSc, Professor of Surgery
• Investigators: Principal Investigator: Ole Thorlacius-Ussing, Professor, DMSc, Department of Gastrointestinal Surgery, Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: September 16, 2019
• First Posted (Actual): September 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 31, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: efficacy; phase II; irreversible electroporation; locally advances pancreatic cancer; nanoknife
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: N-20190013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes