Schimanski, Carl Christoph; Möhler, Markus; Schön, Michael; Cutsem, Eric van; Greil, Richard; Bechstein, Wolf Otto; Hegewisch-Becker, Susanna; Wichert, Götz von; Vöhringer, Matthias; Heike, Michael; Heinemann, Volker; Peeters, Marc; Kanzler, Stephan; Kasper, Stefan; Overkamp, Friedrich; Schröder, Jan; Seehofer, Daniel; Kullmann, Frank; Linz, Bernhard; Schmidtmann, Irene; Smith-Machnow, Victoria; Gockel, Ines; Lang, Hauke; Galle, Peter R.:
LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases-a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial.
In: BMC Cancer
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2: 1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m(2) cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mu g once weekly for 8 weeks, followed by s.c. L-BLP25 930 mu g maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned. Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion.