Open Access Study protocol

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

Carl Christoph Schimanski12122*, Markus Möhler1, Michael Schön2, Eric van Cutsem3, Richard Greil4, Wolf Otto Bechstein5, Susanna Hegewisch-Becker6, Götz von Wichert7, Matthias Vöhringer8, Michael Heike9, Volker Heinemann10, Marc Peeters11, Stephan Kanzler12, Stefan Kasper13, Friedrich Overkamp14, Jan Schröder15, Daniel Seehofer16, Frank Kullmann17, Bernhard Linz18, Irene Schmidtmann19, Victoria Smith-Machnow20, Ines Gockel21, Hauke Lang21 and Peter R Galle1

Author affiliations

1 First Deptartment of Internal Medicine, University Medical Center (UMC), University Hospital of Mainz, Mainz, Germany

2 Department of General and Abdominal Surgery, Municipal Hospital of Karlsruhe, Karlsruhe, Germany

3 Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium

4 Third Department of Internal Medicine, University Medical Center (UMC), University Hospital of Salzburg, Salzburg, Austria

5 Department of General and Abdominal Surgery, University Medical Center (UMC), University Hospital of Frankfurt, Frankfurt, Germany

6 Onkologische Schwerpunktpraxis Eppendorf, Hamburg, Germany

7 First Department of Internal Medicine, University Medical Center (UMC), University Hospital of Ulm, Ulm, Germany

8 Center of Internal Medicine, Robert-Bosch Hospital, Stuttgart, Germany

9 Med. Klinik Mitte, Hospital of Dortmund, Dortmund, Germany

10 Third Department of Internal Medicine, University Hospital of Großhadern, Munich, Germany

11 Department of Oncology, Antwerp University Hospital, Edegem, Belgium

12 Department of Internal Medicine, Leopoldina Hospital, Schweinfurt, Germany

13 Department of Internal Medicine, University Medical Center (UMC), University Hospital of Essen, Essen, Germany

14 Oncologianova GmbH, Recklinghausen, Germany

15 Outpatient center for hematology and oncology, Mühlheim an der Ruhr, Germany

16 Department of General, Visceral and Transplantation Surgery, Campus Virchow Klinikum, Humboldt University, Berlin, Germany

17 First Department of Internal Medicine, Kliniken Nordoberpfalz AG, Klinikum Weiden, Germany

18 Outpatient center for hematology and oncology, Offenburg, Germany

19 Institute of Medical Biometrics, Epidemiology and Informatics (IMBEI), University Medical Center (UMC), University Hospital of Mainz, Mainz, Germany

20 iOMEDICO, Freiburg, Germany

21 Department of General and Abdominal Surgery, University Medical Center (UMC), University Hospital of Mainz, Mainz, Germany

22 First Dept. of Internal Medicine, University Medical Center (UMC), University Hospital of Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany

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Citation and License

BMC Cancer 2012, 12:144  doi:10.1186/1471-2407-12-144

Published: 11 April 2012

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