search
Back to results

CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy (CROSSFIRE)

Primary Purpose

Pancreatic Neoplasm

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Irreversible electroporation (IRE)
Stereotactic ablative radiotherapy (SABR)
Sponsored by
Dr. M.R. Meijerink
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Neoplasm focused on measuring Irreversible electroporation (IRE, Stereotactic ablative radiotherapy (SABR, Efficacy, Tumor ablation, Chemotherapy, Locally advanced pancreatic cancer (LAPC)

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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;

Exclusion Criteria:

  • 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;
  • Previous surgical therapy for pancreatic cancer;
  • Second primary malignancy, except adequately treated non-melanoma skin cancer, in situ carcinoma of the cervis uteri or other malignancies treated at least 5 years previously without signs of recurrence;
  • Allergic to contrast agent.
  • Any implanted stimulation device;
  • Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study;
  • Non-removable Self Expanding Metal biliary Stent (SEMS), which cannot be removed during surgery.

  • Contra-indications for MRI since no safety data for 0.35 Tesla MRI scanners are available on electronic devices such as pacemakers or implanted defibrillators, deep brain stimulators, cochlear implants, this constitutes an absolute contraindication for this study, even for devices that have been considered safe for MRI scans with higher field strengths.

    • Patients who have a metallic foreign body in their eye, or who have an aneurysm clip in their brain, cannot have an MRI scan since the magnetic field may dislodge the metal
    • Patients with severe claustrophobia may not be able to tolerate an MRI scan
    • Patients with a hip prosthesis will not be eligible for the MRI scan

Sites / Locations

  • Bart Geboers

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

IRE group

SABR group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Overall survival

Secondary Outcome Measures

Progression free survival
Untreatable progression-free survival (uPFS)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Pain assessment
Pain assessment by using a scale.
Cost-effectiveness analysis
Direct and indirect total cost of care for both treatment arms (cost-effectiveness analysis);
Quality of life of patients treated with IRE/SABR
Assessing quality of life by using questionnaires.
Change in immune status and reactivity after the procedure (IRE/SABR) by assessing the level of immune cells pre- and post-IRE
Measurement of circulating immune cells pre- and post-IRE
Tumor marker CA 19.9

Full Information

First Posted
May 17, 2016
Last Updated
December 18, 2022
Sponsor
Dr. M.R. Meijerink
search

1. Study Identification

Unique Protocol Identification Number
NCT02791503
Brief Title
CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy
Acronym
CROSSFIRE
Official Title
CROSSFIRE Trial: Crossatlantic Randomized Controlled Trial Comparing Outcome in Survival After Systemic Plus Focal Therapy for Inoperable Pancreatic Carcinoma: Radiotherapy Versus Irreversible Electroporation
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
May 30, 2016 (undefined)
Primary Completion Date
September 2022 (Actual)
Study Completion Date
September 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. M.R. Meijerink

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
Pancreatic cancer has the highest mortality rate of all major cancers; 94% of pancreatic cancer patients will die within five years of diagnosis, 74% within the first year of diagnosis; only 6% will survive for more than five years. Surgical resection is the only curative option. However, about 40% present with non-metastatic locally advanced pancreatic carcinoma (LAPC; AJCC stage III). These patients are not eligible for surgical resection because the tumor involves major blood vessels such as the superior mesenteric artery, celiac axis, common hepatic artery and/or portal vein. These patients are currently treated with palliative chemotherapy as first line therapy. 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. 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. The CROSSFIRE-trial is a prospective, randomized controlled phase-II/III trial.The primary aim of this study is to compare the efficacy of chemotherapy and IRE (experimental arm) to the efficacy of chemotherapy and radiation (control arm) in patients with locally advanced, non-resectable, non-metastasized, pancreatic cancer. In total, 138 patients with histologically proven locally advanced pancreatic adenocarcinoma (AJCC stage III), aged ≥ 18 years will be included. Patients with a specific cardiac history (arrhythmias, pacemaker), pre-existent ECG-abnormalities and/or non-retrievable metallic self-expanding biliary stents are excluded from participation. Patients will be randomly allocated to receive either chemotherapy and radiation (control arm) or chemotherapy and IRE (experimental arm).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasm
Keywords
Irreversible electroporation (IRE, Stereotactic ablative radiotherapy (SABR, Efficacy, Tumor ablation, Chemotherapy, Locally advanced pancreatic cancer (LAPC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IRE group
Arm Type
Experimental
Arm Description
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.
Arm Title
SABR group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Irreversible electroporation (IRE)
Other Intervention Name(s)
NanoKnife
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Stereotactic ablative radiotherapy (SABR)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Time Frame
From date of randomization until the date of date of death from any cause, assessed up to 100 months
Secondary Outcome Measure Information:
Title
Progression free survival
Time Frame
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
Title
Untreatable progression-free survival (uPFS)
Time Frame
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
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] within 90 days after the procedure (IRE/SABR)
Title
Pain assessment
Description
Pain assessment by using a scale.
Time Frame
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
Title
Cost-effectiveness analysis
Description
Direct and indirect total cost of care for both treatment arms (cost-effectiveness analysis);
Time Frame
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
Title
Quality of life of patients treated with IRE/SABR
Description
Assessing quality of life by using questionnaires.
Time Frame
From date of randomization until the date of date of death from any cause, whichever came first, assessed up to 100 months by using questionnaires
Title
Change in immune status and reactivity after the procedure (IRE/SABR) by assessing the level of immune cells pre- and post-IRE
Description
Measurement of circulating immune cells pre- and post-IRE
Time Frame
Up to 3 months post-procedure
Title
Tumor marker CA 19.9
Time Frame
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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; Exclusion Criteria: 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; Previous surgical therapy for pancreatic cancer; Second primary malignancy, except adequately treated non-melanoma skin cancer, in situ carcinoma of the cervis uteri or other malignancies treated at least 5 years previously without signs of recurrence; Allergic to contrast agent. Any implanted stimulation device; Any condition that is unstable or that could jeopardize the safety of the subject and their compliance in the study; Non-removable Self Expanding Metal biliary Stent (SEMS), which cannot be removed during surgery. Contra-indications for MRI since no safety data for 0.35 Tesla MRI scanners are available on electronic devices such as pacemakers or implanted defibrillators, deep brain stimulators, cochlear implants, this constitutes an absolute contraindication for this study, even for devices that have been considered safe for MRI scans with higher field strengths. Patients who have a metallic foreign body in their eye, or who have an aneurysm clip in their brain, cannot have an MRI scan since the magnetic field may dislodge the metal Patients with severe claustrophobia may not be able to tolerate an MRI scan Patients with a hip prosthesis will not be eligible for the MRI scan
Facility Information:
Facility Name
Bart Geboers
City
Amsterdam
State/Province
Non-US/Non-Canadian
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy

We'll reach out to this number within 24 hrs