Annual Meeting Proceedings Part 1 - American Society of Clinical ...

238s Gastrointestinal (Colorectal) Cancer
TPS3641^ General Poster Session (Board #39F), Mon, 8:00 AM-12:00 PM
A randomized, double-blind, placebo-controlled, multicenter, multinational,
phase II trial of L-BLP25 in patients with colorectal carcinoma
following R0/R1 hepatic metastasectomy. Presenting Author: Carl Christoph
Schimanski, University of Mainz, Mainz, Germany
Background: Approximately 15-20% of patients diagnosed with colorectal
cancer (crc) develop metastatic disease. Surgical resection remains the
only potentially curative treatment. 5-year survival following R0-resection
of liver metastases lies ~28 -39%. Recurrence occurs in ~70% of pts.
Adjuvant chemotherapy has not significantly improved clinical outcomes.
The primary objective of the LICC trial (L-BLP25 in Colorectal Cancer) is to
analyze whether L-BLP25, an active cancer immunotherapy, extends
recurrence-free survival (RFS) time over placebo in colorectal cancer pts
following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1
glycoprotein, which is highly expressed in hepatic metastases from crc. In a
phase IIB trial, L-BLP25 showed acceptable tolerability and a trend toward
longer survival in pts with stage IIIB NSCLC. Methods: This is a multinational,
phase II, multicenter, randomized, double-blind, placebo-controlled
trial with a sample size of 159 pts from 20 centers in 3 countries. Pts must
have stage IV cr adenocarcinoma limited to liver metastases. Following
complete resection of the primary tumor and all syn-/metachronous
metastases, eligible pts 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 sc L-BLP25 930 �g once weekly for 8 weeks, followed by
maintenance doses at 6-week (years 1 and 2) and 12-week (year 3)
intervals until recurrence. In the control arm, CP is replaced by saline
solution and L-BLP25 by placebo. Primary endpoint: RFS time. Secondary
endpoints: OS time, safety status, tolerability, RFS/OS in MUC-1 positive
cancers. Exploratory immune response analyses are planned. First recruitment
was of Q3 2011. To date, 8 of 20 centers are initiated and 4 pts
recruited. Completion of recruitment is scheduled for Q3 2013. Primary
endpoint will be assessed in Q3 2016: Follow-up will end Q3 2017. No
interim analysis is planned. Design and implementation of this vaccination
study in colorectal cancer is feasible. No major issues identified during
setup of the study.
TPS3643 General Poster Session (Board #39H), Mon, 8:00 AM-12:00 PM
ATTACHE: A phase III, multicenter, randomized comparison of chemotherapy
given prior to and post surgical resection versus chemotherapy
given post surgical resection for hepatic metastases from colorectal cancer.
Presenting Author: Jonathan Fawcett, Queensland Liver Transplant Service,
Brisbane, Australia
Background: No randomized studies have directly compared the role of
peri-operative to adjuvant chemotherapy for resectable liver metastases.
Benefit from post operative compared to peri-operative treatment has been
suggested in a recent retrospective study of 499 patients with resected
colorectal liver metastases which showed improved survival with entirely
post-operative chemotherapy. Given this data and that of the small
randomised trials demonstrating improved surgical outcomes with adjuvant
chemotherapy, the role of entirely post-operative chemotherapy as a means
of improving outcomes while reducing the negative effects of pre-operative
treatment needs to be examined. Methods: 200 patients randomized 1:1 to
6 months of treatment post-operatively or 3 months of treatment preoperatively
and 3 months post-operatively. Site investigators will nominate
chemotherapy schedule (mFOLFOX6, XELOX or FOLFIRI when adjuvant
oxaliplatin received previously) prior to randomisation. Primary endpoint:
proportion of patients in each arm with surgical complications within 30
days. Secondary endpoints: proportion of patients completing planned
chemotherapy, post operative mortality rate (in each group), tolerability
and safety of treatment, response rate by RECIST V1.1 and CEA, time to
progression, time to treatment failure, overall survival, QoL (EORTC
QLQ-C30 and QLQ-LMC21). A planned prospective meta-analysis with
MRC (UK) and NSABP C-11 trials will have sufficient power to examine the
effect of schedule (peri- or post-operative) on progression free survival
(PFS). Eligibility: Patients with histologically proven colorectal cancer with
radiologically confirmed, resectable liver metastases without evidence of
extra-hepatic disease are eligible. Patients with synchronous metastases
who have undergone resection of the primary tumour are eligible but
patients requiring combined resection of primary cancer and liver metastatic
disease are excluded. Patients with involved hilar nodes or wound
implant metastases will not be eligible. Trial Status: Study opened to
accrual August 2011.
TPS3642 General Poster Session (Board #39G), Mon, 8:00 AM-12:00 PM
FOLFIRI plus 5 mg/kg of bevacizumab versus 10 mg/kg as second-line
therapy in patients with metastatic colorectal cancer who have failed
first-line bevacizumab plus oxaliplatin-based therapy: A randomized phase
III study (EAGLE Study). Presenting Author: Masato Nakamura, Aizawa
Hospital, Matsumoto, Japan
Background: There has been much controversy about continuation of
bevacizumab (BV) with a second-line regimen after progression on a
BV-containing first-line regimen. Recently, it was announced that a phase
III study (AIO 0504 / ML 18147) met its primary endpoint of overall
survival. It means BV-based regimen (5 mg/kg) extends survival when
continued beyond initial treatment in patients with metastatic colorectal
cancer(mCRC). The verified data from a randomized phase III study
(E3200) indicates that BV at 10 mg/kg in the second-line setting followed
by BV-naive treatment extends survival. The dose of BV 5 mg/kg could be
lower than the recommended dose in the second-line CRC treatment. Thus
we planned this second line phase III study (EAGLE study) to evaluate the
appropriate dose of BV (5 or 10 mg/kg) with FOLFIRI in patients with mCRC
who have failed BV plus oxaliplatin-based first line regimen. Methods:
EAGLE is a multicenter randomized phase III study of FOLFIRI plus BV 5
mg/kg versus 10 mg/kg in mCRC who have failed BV plus oxaliplatin-based
first line regimen (UMIN000002557).The primary endpoint is PFS. The
secondary endpoints are the toxicity, response rate, time to treatment
failure, OS. Eligible patients were older than 20 years of age, had
histologically proved CRC, ECOG performance status 0 or 1, adequate
organ function, progression or difficult to continue after BV plus oxaliplatinbased
first line regimen, more than four times administration of BV and
oxaliplatin in the first-line. Patients were randomized 1:1 to FOLFIRI with
BV 5mg/kg or 10 mg/kg.The planned sample size was 370 patients to
detect 30% risk reduction (median PFS assumed to be 5.0 months in arm
A, 7.0 months in arm B) with 90% power assuming a two-sided significance
level of 0.05, an accrual time of 2.5 years and a follow-up time of 1
year. Between September 2009 to January 2012, 387 patients were
enrolled at 100 sites in Japan. This phase III study will answer the question
of the appropriate dose of BV after progression on a BV-containing first-line
regimen.
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