Phase II/III of Randomized Controlled Clinical Research on IRE Synchronous Chemotherapy for LAPC
Condition: Locally Advanced Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Previous studies have shown that irreversible electroporation (IRE) preoperative induction
      chemotherapy or adjuvant chemotherapy after IRE can reduce the local recurrence rate of
      locally advanced pancreatic cancer (LAPC) and benefit the survival of patients. According to
      the technical principle of electroporation therapy (EPT), when the cell membrane is
      electroporated, the resistance of cell membrane decreases instantaneously, which promotes the
      drug to enter tumor cells and significantly increases its cytotoxicity and killing effect on
      tumor tissue. The purpose of study is to evaluate the safety and effectiveness of
      simultaneous gemcitabine administration and IRE for treating LAPC. In order to provide new
      ideas for the treatment of LAPC.
    

Detailed description: 
      Pancreatic cancer (PC) is a highly malignant digestive tract tumor that is projected to
      become the second leading cause of cancer-related deaths in both the United States and
      Germany by 2030. The majority of patients have locally advanced pancreatic cancer (LAPC) or
      metastatic pancreatic cancer (MPC) at initial diagnosis; in fact, less than 20% of newly
      diagnosed patients are eligible for surgical resection . The 5-year relative survival rate
      for PC is 8%, and for those cases diagnosed at a distant stage, the 5-year survival is 3%.
      For LAPC, chemotherapy, such as FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and
      oxaliplatin), gemcitabine plus albumin-bound paclitaxel, or gemcitabine monotherapy, is
      considered first-line therapy.

      However, chemotherapy has been shown to have little effect on the survival rate of those with
      PC, leading to the evaluation of new interventions. Recently, radiofrequency, microwave,
      cryoablation, and other minimally invasive therapies have been proven to be effective in the
      treatment of LAPC. However, these temperature-dependent ablation methods may damage
      peripancreatic vessels, the duodenum, and the bile and pancreatic duct, leading to high
      morbidity and mortality. Irreversible electroporation (IRE) is a new, nonthermal local
      ablation method for solid tumors. It utilizes targeted delivery of millisecond electrical
      pulses that induce permeabilization of cell membranes, resulting in unrecoverable nanoscale
      perforation and apoptotic cell death without damaging the structural components of tissues.

      IRE has recently been found to have unique advantages and effectiveness in the treatment of
      PC. There are different proportions of exposed cells in the IRE zone and the reversible
      electroporation (RE) zone with a standard default electric field intensity of 1500 V per cm .
      In the RE zone, the permeability of the cell membranes caused by electroporation can promote
      the diffusion of drugs into the cells and increase cytotoxicity , which might further
      increase tumor treatment efficacy. Indeed, a preclinical experiment has proven that IRE may
      potentially reduce local recurrence by allowing increased gemcitabine tissue delivery in the
      RE zone.

      With the above in mind, this randomized, controlled clinical trial combined systemic
      chemotherapy and IRE for the treatment of LAPC. The aim of this study was to assess the
      progression-free survival (PFS), objective response rate (ORR) and adverse events after
      combined therapy, with a view of achieving a more effective treatment method for LAPC.
    

Intervention name(s): Irreversible electroporation; Gemcitabine
Intervention type(s): Device; Drug
Intervention description(s): During the IRE process, we employed a CT scanner and an ultrasound system to guide percutaneous insertion of the electrode probes (one main electrode and one to three standard electrodes were used per treatment). The electrode number, electrode-insertion mode and intraoperative parameters were decided upon during pretreatment planning. The IRE parameters were visually simulated in the pulse generator and set up as follows: energy was applied at 1500 V/cm for 90 ms/pulse for a total of 7-9 pulses. After an initial testing pulse train was discharged to establish the best voltage value, the remaining 80 pulses were completed in 1-2 minutes. After ablation, we confirmed completion of IRE by measuring real-time resistance or current changes, in addition to intraoperative ultrasound and CT.; Gemcitabine hydrochloride (Qilu pharmaceutical [Hainan] Co., Ltd. Haikou, China] was administered by intravenous infusion at a dose of 1000 mg/m2.
Intervention MeSH terms: Gemcitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: gemcitabine; pancreatic adenocarcinoma; Irreversible electroporation; overall survival time