PrE0204: A multi-institutional, single arm, two-stage phase II trial of nab-paclitaxel and gemcitabine for first-line treatment of patients with advanced or metastatic cholangiocarcinoma—A PrECOG LLC study.

4072 Background: Pts with advanced or metastatic cholangiocarcinoma (CCA) have limited response to current chemotherapy regimens and poor overall survival (OS). Nab-Paclitaxel (nabPAC) can increase the intra-cellular concentration of gemcitabine (GEM) through depletion of its metabolizing enzyme, cytidine deaminase (CDA). We investigated the nabPAC+GEM combination in a ph II single arm trial in advanced or metastatic CCA pts with exploratory biomarker evaluation, including CDA, hENT1, SPARC and circulating tumor cells (CTCs). Methods: Key eligibility criteria: advanced or metastatic CCA with no prior systemic chemotherapy, age > 18, ECOG PS 0-1 and Child-Pugh < 8. Pts received nabPAC (125 mg/m2 IV) and GEM (1000 mg/m2 IV) days 1, 8 and 15 Q4 weeks until progression. Primary endpoint: progression-free survival (PFS) rate at 6 months. Secondary endpoints: safety, time to progression (TTP), objective response (ORR) and disease control rates (DCR), median PFS and OS, as well as correlation of change in CA 19-9 to clinical efficacy. The study required > 43 of 67 evaluable patients alive and progression-free at 6 months to conclude the 6-month PFS rate is at least 70% against a null hypothesis of 55% based on historical data. Results: 73 eligible patients (41.1% male, 91.8% Caucasian, 45.2% ECOG PS 0) were enrolled across 22 sites with a median age of 62 (range 36-87) years and received a median of 6 (range 1-18) cycles. The primary endpoint of PFS rate at 6 months was 54.7% on intention to treat analysis. Response evaluation is underway and will be reported at the meeting. The median PFS and OS were 6.5 (95% CI, 5.1-7.7) and 10.3 (95% CI, 9.1-14.6) months, respectively. The safety profile of nabPAC+GEM was similar to that reported in ph III MPACT trial. The most common treatment-related G3/4 toxicities were neutropenia (24.3%), fatigue (13.5%) and anemia (12.2%). Five patients remain on the trial. Exploratory analyses are pending. Conclusions: The observed PFS rate at 6 months with nabPAC+GEM in CCA is insufficient to reject the null hypothesis of 55% PFS at 6 months, and appears to be as effective as the historical control. Clinical trial information: NCT02181634.