Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC)

Abstract

Background According to current guidelines, treatment of patients with hepatic oligometastasis in pancreatic cancer is not reflected and systemic chemotherapy is recommended in those patients. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from clinical trials addressing this particular patient group is not available. Methods In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. The clinical trial will focus on a well-defined patient collective with metastatic load limited to the liver as target organ with a maximum of five metastases. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (nal-IRI + OX+ 5-FU/FA, NAPOX) was chosen as neoadjuvant chemotherapy; the choice was based on an ongoing clinical study in which NAPOX appeared manageable, with promising anti-tumor activity in first-line treatment of patients with metastatic pancreatic adenocarcinoma. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. Discussion This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Trial registration numbers EudraCT 2019–002734-37; NCT04617457.

Understanding Tricky Cellular and Molecular Interactions in Pancreatic Tumor Microenvironment: New Food for Thought

“…The NAPOLI1 trial ( 173 , 174 ) showed the efficacy of Nal-IRI in combination with 5-fluorouracil and leucovorin to increase both overall survival and progression-free survival (PFS) in both non-metastatic and metastatic patients. The HOLIPANC trial ( 175 ) proved that neoadjuvant combination of Nal-IRI, oxaliplatin, 5-fluouracil, and folinic acid (NAPOX) had a considerable antitumor effect and increased overall survival of patients with a metastatic disease.…”

Cytokeratin 6 identifies basal-like subtypes of pancreatic ductal adenocarcinoma with decreased survival

“…Expanded therapy regimes are not only limited to the chemotherapeutic arm. The HOLIPANC study is already softening paradigms, which have been described in the guidelines for decades (Gebauer et al 2021). Hence, the patients with oligometastatic adenocarcinoma of the pancreas are receiving neoadjuvant therapy before undergoing a subsequent curative resection.…”

“…Hence, the patients with oligometastatic adenocarcinoma of the pancreas are receiving neoadjuvant therapy before undergoing a subsequent curative resection. Since the study is still including patients, the first results are still pending (Gebauer et al 2021). Surely, exact Membership of the PANCALYZE Study Group is provided in the subtypes of pancreatic adenocarcinoma are required to be described to facilitate clinical decision-making and to further enhance the personalized oncology (Grullich and Kalle 2012).…”

Surgical resection of pancreatic cancer with synchronous hepatic oligometastases: Real benefit or selection bias?

“…3 The Hepatic Oligometastatic Pancreatic Cancer (HOLIPANC) study (NCT04617457) is a non-randomized, multicenter, single-arm phase II clinical trial for pancreatic cancer patients with hepatic oligometastases receiving neoadjuvant combination chemotherapy, where those with stable or responsive disease and a resectable primary tumor will undergo synchronous resection of the tumor and hepatic metastases. 6 The SCANPAN-1 trial (NCT05271110) is a Scandinavian multicenter study that will prospectively investigate the role of surgery or ablation of liver metastases from pancreatic cancer.…”