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.

Abstract

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/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg 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.

TRIAL REGISTRATION:

EudraCT Number 2011-000218-20.

• Authors: Carl Christoph Schimanski, Markus Möhler, Michael Schön, Eric van Cutsem, Richard Greil, Wolf Otto Bechstein, Susanna Hegewisch-Becker, Götz von Wichert, Matthias Vöhringer, Michael Heike, Volker Heinemann, Marc Peeters, Stephan Kanzler, Stefan Kasper, Friedrich Overkamp, Jan Schröder, Daniel Seehofer, Frank Kullmann, Bernhard Linz, Irene Schmidtmann, Victoria Smith-Machnow, Ines Gockel, Hauke Lang, Peter R Galle
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 144 (Apr 11 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 22494623 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• L-BLP25
• Membrane Glycoproteins

Topics

• Adenocarcinoma (mortality, prevention & control, secondary, surgery)
• Adult
• Cancer Vaccines (therapeutic use)
• Colorectal Neoplasms (pathology, surgery, therapy)
• Combined Modality Therapy (methods)
• Double-Blind Method
• Female
• Humans
• Liver Neoplasms (mortality, prevention & control, secondary, surgery)
• Male
• Membrane Glycoproteins (therapeutic use)
• Neoplasm Recurrence, Local (mortality, prevention & control)
• Neoplasm Staging
• Survival Analysis