Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial

Abstract

Background Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26–34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. Methods The “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. Discussion The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. Trial registration Dutch Trial RegistryNL4997. Registered on December 29, 2015. ClinicalTrials.govNCT03690323. Retrospectively registered on October 1, 2018

Added value of 3T MRI and the MRI-halo sign in assessing resectability of locally advanced pancreatic cancer following induction chemotherapy (IMAGE-MRI): prospective pilot study

“…Surgical resection was not feasible in the remaining 8 patients, because of metastatic disease ( n = 4, 20.0%) or extensive local regional tumor ingrowth from peripancreatic vasculature ( n = 4, 20.0%). From this latter group, all patients were treated with radiofrequency ablation in the setting of a clinical trial [ 38 ]. See Supplementary Digital Content 2 for surgical and pathology outcome.…”

Image-Guided Percutaneous Ablation for Primary and Metastatic Tumors

“…The role of tumor ablation in pancreatic cancer is still understudied and there have been no completed trials that compare multiple ablation modalities [ 115 , 117 ]. Examples of the major ongoing trials are the “Pancreatic Locally Advanced Unresectable Cancer Ablation” (PELICAN) trial [ 118 ], which is an international multicentric superiority RCT investigating the effect of RFA in combination with chemotherapy in 228 patients across 16 centers in the Netherlands and four European centers, and the CROSSFIRE trial in the Netherlands, which compares the efficacy of IRE and chemotherapy (FOLFIRINOX) to the efficacy of FOLFIRINOX and stereotactic ablative radiotherapy (SABR) in 138 patients with non-resectable, non-metastasized, locally advanced pancreatic cancer (LAPC) [ 117 ].…”

Pancreatic Cancer: Challenges and Opportunities in Locoregional Therapies

“…Interestingly, a randomised controlled trial revealed a conflicting conclusion that radiofrequency ablation alone showed the lack of superiority over traditional chemotherapy, and it should only be considered a part of multimodal therapies for localised advanced PC [ 151 ]. To investigate the effect of RFA and chemotherapy against standard chemotherapy alone in PC, a current multicentre randomised clinical trial is being conducted [ 152 ]. However, to our knowledge, no randomised clinical trial comparing the outcome of RFA and surgical resection in PC has been conducted.…”

“…As a result, local control of the disease is the main indication of locoregional therapies. For instance, locoregional ablative therapies are introduced with other treatments when the tumour is not suitable for surgery, or in advanced stages for debulking of the tumours rather than complete tumour necrosis [ 152 ], and as consolidative treatments in stable diseases. Unfortunately, locally advanced pancreatic cancer is associated with a dismal prognosis; in this case, ablation therapies are introduced as palliative therapies [ 241 ].…”