Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02791503
Other study ID # NL55158.029.15
Secondary ID
Status Completed
Phase N/A
First received
Last updated
Start date May 30, 2016
Est. completion date September 2022

Study information

Verified date December 2022
Source Amsterdam UMC, location VUmc
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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).


Recruitment information / eligibility

Status Completed
Enrollment 74
Est. completion date September 2022
Est. primary completion date September 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years to 100 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
Netherlands Bart Geboers Amsterdam Non-US/Non-Canadian

Sponsors (1)

Lead Sponsor Collaborator
Dr. M.R. Meijerink

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall survival From date of randomization until the date of date of death from any cause, assessed up to 100 months
Secondary 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
Secondary 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
Secondary 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)
Secondary Pain assessment Pain assessment by using a scale. 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
Secondary Cost-effectiveness analysis Direct and indirect total cost of care for both treatment arms (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
Secondary Quality of life of patients treated with IRE/SABR Assessing quality of life by using questionnaires. 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
Secondary 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 Up to 3 months post-procedure
Secondary Tumor marker CA 19.9 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
See also
  Status Clinical Trial Phase
Completed NCT01354795 - Prospective Study Comparing Methods of Obtainment of Specimen After EUS-FNA in Patients With Peri-pancreatic Mass N/A
Completed NCT00958841 - Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin Phase 2
Terminated NCT00249301 - A Study of MLN8054 in Patients With Advanced Solid Tumors Phase 1
Recruiting NCT06122896 - Prospective Screening for Pancreatic Ductal Adenocarcinoma in High-Risk Individuals Early Phase 1
Terminated NCT02602067 - 131Iodine-Tenatumomab Treatment in Tenascin-C Positive Cancer Patients Phase 1
Recruiting NCT06411795 - Rectus Sheath Block With Liposomal Bupivacaine Versus Thoracic Epidural Analgesia for Pain Control Following Pancreatoduodenectomy Phase 2
Completed NCT03622229 - EUS-FNB for Solid Pancreatic Lesions: Side-fenestrated Vs Fork-tip Needle N/A
Recruiting NCT06400472 - A Study of LY4170156 in Participants With Selected Advanced Solid Tumors Phase 1
Recruiting NCT05786716 - DETERMINE Trial Treatment Arm 04: Trastuzumab in Combination With Pertuzumab in Adult, Teenage/Young Adult and Paediatric Patients With Cancers With HER2 Amplification or Activating Mutations Phase 2/Phase 3
Completed NCT03322592 - EUS-FNB With ROSE Vs. EUS-FNB Without ROSE N/A
Completed NCT05745415 - Cancer Stem Cell Specific Aptamer's Ability to Detect Blood Circulating Cancer Stem Cells and Its Role as a Predictor of Prognosis in Pancreatic Cancer
Recruiting NCT05083247 - Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma Phase 2
Completed NCT00436423 - A Phase Ⅱ Study of Gemcitabine Combination With TS-1 in Patient With Advanced or Recurred Pancreatic Cancer Phase 2
Completed NCT02900950 - Multicolour Versus Monocolour Specimens Inking After Pancreaticoduodenectomy for Periampullary Cancer N/A
Completed NCT00711191 - A Study On An Immunostimulant Antibody In Combination With Chemotherapy For Advanced Cancer Of The Pancreas Phase 1
Completed NCT00222898 - Cancer Detection in Pancreatic Cysts N/A
Completed NCT00034281 - Safety and Tolerability Study of TAK-165 in Subjects With Tumors Expressing HER2 Phase 1
Completed NCT00005926 - Gemcitabine, Herceptin and Radiation to Treat Cancer of the Pancreas Phase 2
Recruiting NCT04164017 - Impact of Suction in the EUS-guided Fine Needle Biopsy of Solid Pancreatic Lesions N/A
Recruiting NCT05687123 - Testing the Addition of Sunitinib Malate to Lutetium Lu 177 Dotatate (Lutathera) in Pancreatic Neuroendocrine Tumors Phase 1