CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy

NCT02791503 | Completed DMC

• 1 other identifier: NL55158.029.15
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Irreversible electroporation (IRE) is a promising new ablation technique to fight pancreatic cancer. The primary aim of the CROSSFIRE trial is to compare the efficacy (in terms of overall survival) of FOLFIRINOX and IRE (experimental arm) to the efficacy of FOLFIRINOX and stereotactic ablative radiotherapy (SABR) (control arm) in patients with locally advanced, non-resectable, non-metastasized, pancreatic cancer (LAPC). Secondary outcomes are progression free survival, safety/toxicity, immunomodulation, tumor marker Cancer Antigen (CA) 19.9, quality of life (QoL), and total direct and indirect costs for each treatment arm (cost-effectiveness analysis).

Conditions

Pancreatic Neoplasm

Keywords

Irreversible electroporation (IRE; Stereotactic ablative radiotherapy (SABR; Efficacy; Tumor ablation; Chemotherapy; Locally advanced pancreatic cancer (LAPC)

Outcome Measures

Primary Outcomes (1)

• Overall survival

  From date of randomization until the date of date of death from any cause, assessed up to 100 months

Secondary Outcomes (8)

• Progression free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Untreatable progression-free survival (uPFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] within 90 days after the procedure (IRE/SABR)

• Pain assessment

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months by using the a scale

• Cost-effectiveness analysis

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Study Arms (2)

IRE group

EXPERIMENTAL

FOLFIRINOX + IRE For patients diagnosed with LAPC, a combination of chemotherapy plus local tumor destruction using irreversible electroporation (IRE), a novel tumor ablation technique, has recently shown great promise. IRE is based on permeabilization of the cell membrane through electrical pulses leading to apoptosis. Theoretically, IRE only affects viable tumor tissue, leaving surrounding vital structures relatively intact. It is therefore considered to cause less morbidity than thermal ablative strategies.

Procedure: Irreversible electroporation (IRE)

SABR group

ACTIVE COMPARATOR

FOLFIRINOX + SABR Focal therapy using external beam radiation therapy (EBRT) may further improve survival, but outcome remains poor. Stereotactic ablative radiotherapy (SABR) is a form of EBRT that has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.

Procedure: Stereotactic ablative radiotherapy (SABR)

Interventions

Irreversible electroporation (IRE) PROCEDURE

IRE is based on permeabilization of the cell membrane through electrical pulses leading to apoptosis. Theoretically, IRE only affects viable tumor tissue, leaving surrounding vital structures relatively intact. It is therefore considered to cause less morbidity than thermal ablative strategies.

Also known as: NanoKnife

IRE group

Stereotactic ablative radiotherapy (SABR) PROCEDURE

Stereotactic ablative radiotherapy (SABR) is a form of external beam radiation that has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.

SABR group

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Maximum tumor diameter ≤ 5 cm;
• Histological or cytological confirmation of pancreatic adenocarcinoma;
• Age \> 18 years;
• ASA-classification 0 - 3; World Health Organisation scale (WHO) performance status 0 - 1 ;
• Adequate bile drainage in case of biliary obstruction;
• Written informed consent;

You may not qualify if:

• Resectable pancreatic adenocarcinoma as discussed by our multidisciplinary hepatobiliary team;
• The presence of suspect lymph nodes
• Stage IV pancreatic carcinoma;
• Trans-mucosal tumor invasion into surrounding duodenum or stomach;
• 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);
• Ventricular cardiac arrhythmias requiring anti-arrhythmic therapy or pacemaker (beta blockers for antihypertensive regimen are permitted; atrial fibrillation is not contra-indicated);
• 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 prior to the procedure;
• Radiotherapy prior to study enrollment;

Sponsors & Collaborators

• Dr. M.R. Meijerink: lead

Study Sites (1)

Bart Geboers

Amsterdam, Non-US/Non-Canadian, Netherlands

Location

Related Publications (2)

• Geboers B, Timmer F, Vos D, Scheffer H, Bakker J, Ruarus A, Vroomen L, Stam A, Lougheed S, Schouten E, Puijk R, van den Tol P, Lagerwaard F, de Vries J, Bruynzeel A, Meijerink M, de Gruijl T. Systemic immunomodulation by irreversible electroporation versus stereotactic ablative body radiotherapy in locally advanced pancreatic cancer: the CROSSFIRE trial. J Immunother Cancer. 2025 Mar 26;13(3):e010222. doi: 10.1136/jitc-2024-010222.

  PMID: 40139834 DERIVED

• Timmer FEF, Geboers B, Ruarus AH, Vroomen LGPH, Schouten EAC, van der Lei S, Vos DJW, Dijkstra M, Schulz HH, Bakker J, van den Bemd BAT, van den Tol PM, Puijk RS, Lissenberg-Witte BI, de Gruijl TD, de Vries JJJ, Lagerwaard FJ, Scheffer HJ, Bruynzeel AME, Meijerink MR. MRI-guided stereotactic ablative body radiotherapy versus CT-guided percutaneous irreversible electroporation for locally advanced pancreatic cancer (CROSSFIRE): a single-centre, open-label, randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2024 May;9(5):448-459. doi: 10.1016/S2468-1253(24)00017-7. Epub 2024 Mar 19.

  PMID: 38513683 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Electroporation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: dr.

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 6, 2016
• Study Start: May 30, 2016
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: December 20, 2022

Record last verified: 2022-12

Locations

NL (1)