Resectable

Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive cancer with poor prognosis. ECCA can be further subcategorised in perihilar and distal cholangiocarcinoma (pCCA and dCCA). Surgical resection is the only potential cure, but only one-third of patients are eligible. Even among those deemed resectable, a significant portion (≈30%) experience disease progression before surgery, while another 30% are found unresectable during exploration. High recurrence rates and postoperative complications further limit survival, with 5-year overall survival ranging from 13% (R1 resection) to 40% (R0 resection). Given the long preoperative work-up period and lack of treatment during this phase, a neoadjuvant approach may improve outcomes by increasing R0 resections, reducing recurrence, and optimizing patient selection. This multicenter, randomized phase 2B/3 trial aims to assess whether neoadjuvant gemcitabine and cisplatin plus perioperative pembrolizumab improves event-free survival in patients with resectable and borderline resectable pCCA and dCCA.

The primary objective of this trial is to investigate whether the addition of 3 additional neo-adjuvant cycles of chemotherapy (doxorubicin based chemotherapy) to standard management according to the ISG-STS 10-01 study (3 cycles of neoadjuvant doxorubicin based chemotherapy + surgery +/- radiotherapy) improves the outcome of high-risk CINSARC patients with resectable soft-tissue sarcoma (STS). Primary endpoint is metastatic progression-free survival (M-PFS, after 3 years of follow-up).