Electrochemotherapy of Posterior Resection Surface for Lowering Disease Recurrence Rate in Pancreatic Cancer (PanECT Study) (PanECT)

Electrochemotherapy of Posterior Resection Surface for Lowering Disease Recurrence Rate in Pancreatic Cancer

The aim of the study is to evaluate toxicity and effectiveness of electrochemotherapy (ECT) with bleomycin in pancreatic cancer in clinical study phase I and II. After surgical resection of pancreatic cancer, the posterior resection surface will be treated with ECT with the intention to lower disease recurrence rate.

The study will include 20 patients in phase I clinical study and additional 20 patients in phase II clinical study (or in the extension of the clinical study), which will fulfill inclusion criteria.

Treatment effectiveness will be evaluated by US or CT imaging, to detect early local recurrence of the disease. Long term effectiveness of the treatment will be evaluated by frequent and precise patient follow-up. During follow-up clinical examination, laboratory tests, tumor markers (Ca 19-9 and CEA) and US/CT imaging will be performed.

The secondary objectives of the trial are to quantify the impact of the treatment on the patient's quality of life, tolerance to the therapy and suitability for larger study to be conducted.

Study Overview

• Status: Terminated
• Conditions: Pancreas Cancer
• Intervention / Treatment: Procedure: Electrochemotherapy - electroporation with Cliniporator Vitae® and chemotherapy drug Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

Detailed Description

The study will be conducted on patients with resectable pancreatic cancer. 20 patients will be included in phase I clinical study and additional 20 patients in phase II clinical study (or in the extension of the clinical study).

After surgical resection of pancreatic cancer, the posterior resection surface will be treated with purpose to lower disease recurrence rate. Plate electrodes will be used for ECT treatment, the electrodes will be placed between choledochal cut-end, truncus celiacus, remaining of the pancreas and aortal lymph nodes.

ECT will be performed within 8-28 min after intravenous in bolus administration of bleomycin (15 mg/m2). Triggering of electric pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart.

All patients will be treated after the procedure has been thoroughly described to them and have signed informed consent.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana, Ljubljana, Slovenia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with resectable pancreatic cancer.
2. Histologically confirmed and/or based on radiological imaging and laboratory tests confirmed pancreatic cancer by multidisciplinary team for pancreatic tumors.
3. Age more than 18.
4. Life expectancy more than 3 months.
5. Performance status - Karnofsky ≥ 70 or WHO < or 2.
6. Treatment free interval 2-5 weeks, depending on the drugs used.
7. Patient must be mentally capable of understanding the information given.
8. Patient must give informed consent.
9. Patient must be discussed at the multidisciplinary team for pancreatic tumors before entering the trial.

Exclusion Criteria:

1. Secondary primary tumor, except surgically treated noninvasive cancer of cervix, or surgically or irradiated basal cell carcinoma.
2. Proven visceral, bone or diffuse metastases.
3. Life-threatening infection and/or heart failure and/or liver failure and/or renal failure (creatinine more than 150 µmol/L) other severe systemic pathologies.
4. Significant reduction in respiratory function.
5. Age less than 18 years.
6. Cumulative dose of 250 mg/m2 bleomycin received.
7. Allergic reaction to bleomycin.
8. Patients with epilepsy.
9. Patients with arrhythmias.
10. Patients with heart failure or pacemaker.
11. Pregnancy.
12. Patient incapable of understanding the aim of the study or disagree with the entering into the clinical study.

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: Experimental group; Cliniporator Vitae® and chemotherapy drug Bleomycin PHC 15 e. (United States Pharmacopeia - USP)

Procedure: Electrochemotherapy - electroporation with Cliniporator Vitae® and chemotherapy drug Bleomycin PHC 15 e. (United States Pharmacopeia - USP); Procedure: Electrochemotherapy Exploration, anesthesia, pancreatic cancer resection, bleomycin administration, electroporation, formation of all anastomoses. Device: Cliniporator Vitae® Positioning of plate electrodes according to landmarks, 8-28 min after administration of bleomycin application of electric pulses (8 pulses, duration 100 microseconds, frequency 8 Hz with amplitude adequate to cover the whole treated lesion with electric field necessary for reversible plasma membrane permeabilization, approximately 1000V/cm), removal of electrodes. The maximum duration of procedure is 90 minutes, after liver mobilization. Drug: Bleomycin PHC 15 e. (United States Pharmacopeia - USP) Intravenous bolus administration of bleomycin (15 mg/m2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of feasibility and safety	Every patient will be closely followed-up after operation with clinical examination and blood tests (hemogram, comprehensive metabolic panel, liver panel) according to the study protocol (day 1, 3, 7 after operation). In case of detected abnormalities additional imaging (US and/or CT) will take place. Findings will be noted and reported in line with Clavien-Dindo classification of surgical complications. The primary measure is to detect complications after surgery and to determine whether the complication is related to electrochemotherapy treatment or not.	7 days after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	Disease-free survival is defined as the amount of time a subject survives without disease recurrence after treatment. Recurrence is defined as significant elevation of tumor markers Ca19-9 and CEA after operation (normal value of Ca19-9 is under 37.0 kU/L, normal value of CEA is under 4.2 µg/L). The appearance of one or more lesions on imaging investigation (US and/or CT) is also considered a recurrence. The tumor markers and imaging investigations will be performed according to study protocol (tumor markers 1, 3, 6, 12 and 24 months after operation; imaging 1, 3, 6, 12, 18 and 24 months after operation - the imaging method will be CT or MR with or without contrast, with the exception of 1 and 18 months after the operation when an US will be performed).	1, 3, 6, 12, 18 and 24 months after operation
Overall Survival	Overall survival is defined as the amount of time a subject survives after therapy. Patient enrolled in the study will be followed up for at least five years. During first two years after surgery follow-up will be as written above, after that period patient will be followed-up according every 6 months.	From the time of surgical treatment until 5 years after surgery

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Institute of Oncology Ljubljana
• Investigators: Principal Investigator: Mihajlo Djokic, MD, PhD, University Medical Centre Ljubljana, Ljubljana, Slovenia; Study Director: Blaz Trotovsek, MD, PhD, University Medical Centre Ljubljana, Ljubljana, Slovenia; Study Director: Gregor Sersa, PhD, Institute of Oncology, Ljubljana, Slovenia; Study Chair: Zan Cebron, MD, University Medical Centre Ljubljana, Ljubljana, Slovenia; Study Chair: Miha Petric, MD, University Medical Centre Ljubljana, Ljubljana, Slovenia; Study Chair: David Badovinac, MD, University Medical Centre Ljubljana, Ljubljana, Slovenia; Study Chair: Masa Bosnjak, PhD, Institute of Oncology, Ljubljana, Slovenia; Study Chair: Bostjan Markelc, PhD, Institute of Oncology, Ljubljana, Slovenia; Study Chair: Maja Cemazar, PhD, Institute of Oncology, Ljubljana, Slovenia

Publications and helpful links

General Publications

• Djokic M, Cemazar M, Popovic P, Kos B, Dezman R, Bosnjak M, Zakelj MN, Miklavcic D, Potrc S, Stabuc B, Tomazic A, Sersa G, Trotovsek B. Electrochemotherapy as treatment option for hepatocellular carcinoma, a prospective pilot study. Eur J Surg Oncol. 2018 May;44(5):651-657. doi: 10.1016/j.ejso.2018.01.090. Epub 2018 Feb 2.
• Bimonte S, Leongito M, Granata V, Barbieri A, Del Vecchio V, Falco M, Nasto A, Albino V, Piccirillo M, Palaia R, Amore A, Giacomo Rd, Lastoria S, Setola SV, Fusco R, Petrillo A, Izzo F. Electrochemotherapy in pancreatic adenocarcinoma treatment: pre-clinical and clinical studies. Radiol Oncol. 2016 Feb 16;50(1):14-20. doi: 10.1515/raon-2016-0003. eCollection 2016 Mar 1.
• Tafuto S, von Arx C, De Divitiis C, Maura CT, Palaia R, Albino V, Fusco R, Membrini M, Petrillo A, Granata V, Izzo F; ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy). Electrochemotherapy as a new approach on pancreatic cancer and on liver metastases. Int J Surg. 2015 Sep;21 Suppl 1:S78-82. doi: 10.1016/j.ijsu.2015.04.095. Epub 2015 Jun 27.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Actual): March 9, 2021
• Study Completion (Actual): March 9, 2021

Study Registration Dates

• First Submitted: January 14, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 9, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Pancreatic cancer; Electrochemotherapy; Bleomycin
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Disease Attributes; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Recurrence; Pancreatic Neoplasms; Antineoplastic Agents; Antibiotics, Antineoplastic; Bleomycin
• Other Study ID Numbers: 21K/01/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No