title: 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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  EudraCT Number 2011-000218-20.
authors.affiliation: First Deptartment of Internal Medicine, University Medical Center (UMC), University Hospital of Mainz, Mainz, Germany. schimanski@1-med.klinik.uni-mainz.de
authors.forename: Carl Christoph
authors.initials: CC
authors.lastname: Schimanski
authors.forename: Markus
authors.initials: M
authors.lastname: Möhler
authors.forename: Michael
authors.initials: M
authors.lastname: Schön
authors.forename: Eric
authors.initials: E
authors.lastname: van Cutsem
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Wolf Otto
authors.initials: WO
authors.lastname: Bechstein
authors.forename: Susanna
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: Götz
authors.initials: G
authors.lastname: von Wichert
authors.forename: Matthias
authors.initials: M
authors.lastname: Vöhringer
authors.forename: Michael
authors.initials: M
authors.lastname: Heike
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.forename: Stephan
authors.initials: S
authors.lastname: Kanzler
authors.forename: Stefan
authors.initials: S
authors.lastname: Kasper
authors.forename: Friedrich
authors.initials: F
authors.lastname: Overkamp
authors.forename: Jan
authors.initials: J
authors.lastname: Schröder
authors.forename: Daniel
authors.initials: D
authors.lastname: Seehofer
authors.forename: Frank
authors.initials: F
authors.lastname: Kullmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Linz
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith-Machnow
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary / Q000601:surgery; D000328:Adult; D019496:Cancer Vaccines / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary / Q000601:surgery; D008297:Male; D008562:Membrane Glycoproteins / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D009367:Neoplasm Staging; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines; C518273:L-BLP25; D008562:Membrane Glycoproteins