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

BMC Cancer. 2012 Apr 11;12:144. doi: 10.1186/1471-2407-12-144.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cancer Vaccines
  • L-BLP25
  • Membrane Glycoproteins