Biliary tract cancer (CCC) is associated with a poor prognosis due to mostly advanced stages at diagnosis. Overall survival does not exceed 6 months and the 5-year overall survival rate is less than 5% for patients with advanced or metastatic disease. Advanced CCC shows response to chemotherapy resulting in an improved disease control, improved survival and quality of life (QoL). In the ABC-02 phase III trial, gemcitabine combined with cisplatin compared with gemcitabine alone prolonged PFS (8.0 vs. 5.0 mo) and OS (11.7 vs. 8.1 mo) and is considered as standard of care. So far this regimen has not been compared with other active combination regimen. Irinotecan in combination with 5-FU showed promising results in 1st- and 2nd-line therapy in many GI cancers. In pancreatic adenocarcinomas, the combination of liposomal irinotecan (nal-IRI) plus 5-FU/LV improves survival in a post gemcitabine-based treatment setting. Our research hypothesis is that this regimen compares well with respect to clinical endpoints with the standard of care gemcitabine plus cisplatin in patients with advanced CCC.
NIFE is a randomized study for patients (to be enrolled: n = 92) with locally advanced or metastatic, non-resectable, adenocarcinoma of the biliary tract: Arm A (experimental): Nal-IRI 80 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2, on day 1, cycle q2w), Arm B (standard): Cisplatin 25 mg/m2 and Gemcitabine 1000 mg/m2 on day 1 and 8, cycle q3w. NIFE is an open label, non-comparative, multicenter, two-sided phase II study with an unconnected analysis of the results in both arms against a fixed PFS rate (< 40% at 6 months). The randomization (1:1) is eminent to achieve two comparable patient groups. Primary objective is PFS at 6 months. Key secondary objectives are 3-year OS, PFS, ORR, DCR and QoL/TUDD. There will be a retrospective central surgical and radiological review. Tissue and blood sample collection will be mandatory for biomarker analyses (microdissection and exome sequencing of tumor tissue, ctDNA exome sequencing, transcriptome, miRNA-arrays). Start was in II/2017 in 25 centers in Germany.
Clinical trial identification
NCT03044587, January 23, 2017
Legal entity responsible for the study
AIO Studien gGmbH
T.J. Ettrich: The Trial is sponsored by Baxalta/Shire. Thomas Ettrich was member of an Baxalta/Shire advisory board in 2016. All other authors have declared no conflicts of interest.