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

Published on Apr 29, 2021in Trials1.883
· DOI :10.1186/S13063-021-05248-Y
M.S. Walma1
Estimated H-index: 1
(UU: Utrecht University),
Steffi J.E. Rombouts6
Estimated H-index: 6
(UU: Utrecht University)
+ 41 AuthorsI.Q. Molenaar4
Estimated H-index: 4
(UU: Utrecht University)
Source
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 Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.
References47
Newest
#1M.S. Walma (UvA: University of Amsterdam)H-Index: 1
#2Lilly J Brada (UvA: University of Amsterdam)H-Index: 1
Last. I. Quintus MolenaarH-Index: 31
view all 44 authors...
Abstract Introduction Since current studies on locally advanced pancreatic cancer (LAPC) mainly report from single, high-volume centers, it is unclear if outcomes can be translated to daily clinical practice. This study provides treatment strategies and clinical outcomes within a multicenter cohort of unselected patients with LAPC. Materials and methods Consecutive patients with LAPC according to Dutch Pancreatic Cancer Group criteria, were prospectively included in 14 centers from April 2015 un...
2 CitationsSource
#1Elena Rangelova (KI: Karolinska Institutet)H-Index: 13
#2Agnes Wefer (KI: Karolinska Institutet)H-Index: 2
Last. Marco Del Chiaro (KI: Karolinska Institutet)H-Index: 31
view all 9 authors...
: MINI: The overall survival and the survival after resection of patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer after neoadjuvant therapy (NAT) are similar. Resected patients had better survival than nonresected, irrespective of the type or whether full-dose NAT was given. For all preoperative values of Ca 19-9, surgical resection had positive impact on survival. OBJECTIVE: Neoadjuvant therapy (NAT) has become part of the multimodality treatment for b...
42 CitationsSource
#1Marin StrijkerH-Index: 8
#2Tara M. MackayH-Index: 7
Last. Marc G. BesselinkH-Index: 84
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#1Philip A. Philip (WSU: Wayne State University)H-Index: 76
#2Jill Lacy (Yale University)H-Index: 26
Last. Pascal Hammel (Paris Diderot University)H-Index: 86
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Summary Background Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the phase 3 MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this phase 2 trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer. Methods This internation...
45 CitationsSource
#1Anouk E J Latenstein (UvA: University of Amsterdam)H-Index: 5
Last. Johanna W. Wilmink (UvA: University of Amsterdam)H-Index: 25
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Abstract Background In recent years, new treatment options have become available for pancreatic ductal adenocarcinoma (PDAC) including 5-fluorouracil, leucovorin, irinotecan and oxaliplatin. The impact hereof has not been assessed in nationwide cohort studies. This population-based study aimed to investigate nationwide trends in incidence, treatment and survival of PDAC. Materials and methods Patients with PDAC (1997–2016) were included from the Netherlands Cancer Registry. Results were categori...
26 CitationsSource
#1Samira Fegrachi (UU: Utrecht University)H-Index: 5
#2Marieke S. Walma (UU: Utrecht University)H-Index: 6
Last. Richard van Hillegersberg (UU: Utrecht University)H-Index: 51
view all 13 authors...
Abstract Introduction Radiofrequency ablation (RFA) has been proposed as a new treatment option for locally advanced, unresectable pancreatic cancer (LAPC). In preparation of a randomized controlled trial (RCT), the aim of this phase II study was to assess the safety of RFA for patients with LAPC. Materials and methods Patients diagnosed with LAPC confirmed during surgical exploration between November 2012 and April 2014 were eligible for inclusion. RFA probes were placed under ultrasound guidan...
8 CitationsSource
#1Laura Maggino (University of Verona)H-Index: 14
#2Giuseppe Malleo (University of Verona)H-Index: 8
Last. Roberto Salvia (University of Verona)H-Index: 52
view all 24 authors...
Importance Chemotherapy is the recommended induction strategy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. However, the associated results on an intention-to-treat basis are poorly understood. Objective To investigate pragmatically the treatment compliance, conversion to surgery, and survival outcomes of patients with borderline resectable and locally advanced pancreatic ductal adenocarcinoma undergoing primary chemotherapy. Design, Setting, and Participants Th...
45 CitationsSource
#1Mustafa Suker (EUR: Erasmus University Rotterdam)H-Index: 12
#2B. Groot Koerkamp (EUR: Erasmus University Rotterdam)H-Index: 2
Last. C.H.J. van Eijck (EUR: Erasmus University Rotterdam)H-Index: 30
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Abstract Introduction Locally advanced pancreatic cancer (LAPC) is found in 35% of patients with pancreatic cancer. However, these patients often have occult metastatic disease. Patients with occult metastases are unlikely to benefit from locoregional treatments. This study evaluated the yield of occult metastases during staging laparoscopy in patients with LAPC. Methods Between January 2013 and January 2017 all patients with LAPC underwent a staging laparoscopy after a recent tri-phasic CT-scan...
6 CitationsSource
#1Georgios Gemenetzis (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 17
#2Vincent P. Groot (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 16
Last. Jin He (Johns Hopkins University)H-Index: 40
view all 14 authors...
Objective:The aim of the study was to identify the survival of patients with locally advanced pancreatic cancer (LAPC) and assess the effect of surgical resection after neoadjuvant therapy on patient outcomes.Background:An increasing number of LAPC patients who respond favorably to neoadjuvant thera
115 CitationsSource
Last. Marc G. BesselinkH-Index: 84
view all 18 authors...
Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patient...
24 CitationsSource
Cited By1
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#1Isabella FrigerioH-Index: 17
#2Salvatore PaiellaH-Index: 23
Last. G. FiorentiniH-Index: 14
view all 22 authors...
Abstract null null Background null Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. null null null Methods null This i...
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