Cisplatin and gemcitabine plus ramucirumab or merestinib or placebo in first-line treatment for advanced or metastatic biliary tract cancer: A double-blind, randomized phase 2 trial

Background

Angiogenesis and aberrant MET signaling are implicated in the pathogenesis and progression of invasive biliary tract cancers (BTC), including adenocarcinomas of the gallbladder, intra- and extra-hepatic bile ducts, and ampulla of Vater. Study JSBF (NCT02711553) is a phase 2, multicenter, randomized, double-blinded, multi-arm study designed to evaluate the efficacy and safety of standard of care (SOC) cisplatin and gemcitabine in combination with either merestinib (oral type II MET kinase inhibitor) or ramucirumab (human IgG1 VEGFR2 monoclonal antibody) or respective placebo for the first-line treatment of advanced or metastatic BTC.

Trial design

Patients (n = 300) with advanced or metastatic BTC meeting eligibility requirements will be randomized to IV ramucirumab 8 mg/kg, IV placebo, oral merestinib 80 mg, or oral placebo, in a 2:1:2:1 fashion, and stratified by primary tumor site, geographic region, and presence of metastases. In addition to the randomly assigned treatment, all patients will receive SOC 1st-line treatment with up to 8 cycles of IV cisplatin 25mg/m² + gemcitabine 1000mg/m² on days 1 and 8 of 21-day cycles. IV ramucirumab and placebo will be given on days 1 and 8 of each cycle; oral treatments will be taken daily. Investigational treatment or placebo may continue past 8 cycles until disease progression or a criterion for discontinuation is met. The primary study endpoint is progression-free survival (PFS), analyzed by intention-to-treat. Secondary endpoints are overall survival, objective response, disease control rate, safety, pharmacokinetics, immunogenicity (ramucirumab), and patient reported outcomes. An exploratory endpoint is to correlate biomarkers with safety and clinical outcome; blood, plasma, serum, and tumor tissue collection is mandatory. The study began in May 2016. Primary analysis will occur after a minimum of 210 PFS events in the study have been observed to detect potential superiority of each investigational treatment over pooled control.

Clinical trial identification

NCT02711553

Legal entity responsible for the study

Eli Lilly and Company

Funding

Eli Lilly and Company

Disclosure

J.W. Valle: Eli Lilly- Honorarium.

A. Vogel: Dr. Vogel reports personal from Eli Lilly and Company, outside the submitted work.

All other authors have declared no conflicts of interest.