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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02791503
Recruitment Status : Unknown
Verified June 2016 by Dr. M.R. Meijerink, VU University Medical Center.
Recruitment status was:  Recruiting
First Posted : June 6, 2016
Last Update Posted : June 9, 2016
Sponsor:
Information provided by (Responsible Party):
Dr. M.R. Meijerink, VU University Medical Center

Tracking Information
First Submitted Date  ICMJE May 17, 2016
First Posted Date  ICMJE June 6, 2016
Last Update Posted Date June 9, 2016
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2016)
Overall survival [ Time Frame: From date of randomization until the date of date of death from any cause, assessed up to 100 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2016)
  • 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 ]
  • 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 ]
  • 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) ]
  • Pain assessment [ 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 ]
    Pain assessment by using a scale.
  • 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 ]
    Direct and indirect total cost of care for both treatment arms (cost-effectiveness analysis);
  • Quality of life [ 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 ]
    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 [ Time Frame: Up to 3 months post-procedure ]
    Measurement of circulating immune cells pre- and post-IRE
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy
Official Title  ICMJE CROSSFIRE Trial: Crossatlantic Randomized Controlled Trial Comparing Outcome in Survival After Systemic Plus Focal Therapy for Inoperable Pancreatic Carcinoma: Radiotherapy Versus Irreversible Electroporation
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Neoplasm
Intervention  ICMJE
  • Procedure: Irreversible electroporation (IRE)
    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.
    Other Name: NanoKnife
  • Procedure: Stereotactic ablative radiotherapy (SABR)
    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.
Study Arms  ICMJE
  • Experimental: IRE group
    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.
    Intervention: Procedure: Irreversible electroporation (IRE)
  • Active Comparator: SABR group
    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: Procedure: Stereotactic ablative radiotherapy (SABR)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 1, 2016)
138
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02791503
Other Study ID Numbers  ICMJE NL55158.029.15
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Dr. M.R. Meijerink, VU University Medical Center
Study Sponsor  ICMJE Dr. M.R. Meijerink
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account VU University Medical Center
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP