CROSSFIRE Trial: Comparing the Efficacy of Irreversible Electroporation With Radiotherapy
Condition: Pancreatic Neoplasm
MeSH terms: Pancreatic Neoplasms
Study type: Interventional

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).
    

Intervention name(s): Irreversible electroporation (IRE); Stereotactic ablative radiotherapy (SABR)
Intervention type(s): Procedure; Procedure
Intervention description(s): 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) 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.
Other intervention name(s): NanoKnife
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Irreversible electroporation (IRE; Stereotactic ablative radiotherapy (SABR; Efficacy; Tumor ablation; Chemotherapy; Locally advanced pancreatic cancer (LAPC)