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

276s Gastrointestinal (Noncolorectal) Cancer
TPS4152 General Poster Session (Board #54G), Mon, 8:00 AM-12:00 PM
Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic
vaccinia virus, plus best supportive care (BSC) versus BSC alone in
patients with advanced hepatocellular carcinoma who have failed sorafenib
treatment (TRAVERSE). Presenting Author: James M. Burke, Jennerex,
Inc., San Francisco, CA
Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed
to selectively replicate in and destroy cancer cells with epidermal growth
factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus
GM-CSF expression stimulates tumor vascular disruption and anti-tumor
immunity (Nature Rev Cancer 2009). JX-594 was well-tolerated in Phase 1
trials and was shown to replicate in metastatic tumors following intratumoral
(IT) or intravenous (IV) administration (Lancet Oncol 2008 and
Nature 2011). A randomized dose-finding Phase 2 trial has been completed
with JX-594 in 30 patients with advanced HCC. Treatment with
high-dose JX-594 was associated with prolonged survival vs low-dose
JX-594 (median survival 14.1 mo vs 6.7 mo; Hazard Ratio 0.39, p�0.02)
(AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b
randomized, open-label, multi-center trial of JX-594 plus BSC versus BSC
in patients with advanced HCC who have failed sorafenib treatment.
Approximately 120 patients will be randomized 2:1 to experimental and
control arm respectively. Randomization will be stratified by region (Asian
vs non-Asian); sorafenib intolerant vs refractory; and presence vs absence
of extra-hepatic disease. The primary objective is to determine overall
survival in the 2 arms. Assuming a control median overall survival of 4.0
months and a target hazard ratio of 0.57 (corresponding to an experimental
arm median survival of 7.0 months), 73 events (deaths) will provide 70%
power at 1-sided alpha � 0.05 to detect a difference in overall survival
between the treatment groups using a stratified logrank test. Patients
randomized to JX-594 will receive a dose of 109 plaque forming units (pfu)
IV on Day 1 followed by five IT treatments between Day 8 and Week 18.
Main inclusion criteria are advanced HCC having failed sorafenib (intolerance
or radiographic progression during or � 3 months following last
sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function.
Enrollment has begun on this study with clinical trial registry number
of NCT01387555.
TPS4153 General Poster Session (Board #54H), Mon, 8:00 AM-12:00 PM
The CLARINET study: Assessing the effect of lanreotide autogel on tumor
progression-free survival in patients with nonfunctioning gastroenteropancreatic
neuroendocrine tumors. Presenting Author: Patrick Delavault, Ipsen
Innovation, Paris, France
Background: Somatostatin analogs (SSAs) provide good symptom control in
patients with neuroendrocine tumors (NETs). Clinical studies suggest SSAs
also stabilize tumor growth. In a previous double-blind study (PROMID) in a
mixed functioning and non-functioning gastroenteroNET population (n�85),
octreotide LAR significantly increased time to tumor progression compared
with placebo. The CLARINET study is being undertaken to explore the
antiproliferative effects of SSAs in a more homogeneous population.
Specifically, the CLARINET study is a double-blind, placebo-controlled
trial assessing the effect of 120 mg of lanreotide Autogel (lanreotide Depot
in the USA) on progression-free survival in patients with non-functioning
gastroenteropancreatic NETs (GEP-NETs). Methods: CLARINET is a 96week,
multinational study being conducted in collaboration with UKI NETS
and ENETS in patients with well or moderately differentiated nonfunctioning
GEP-NETs and a proliferation index (Ki67) of �10%. Patients
are stratified by prior tumor progression status and presence/absence of
previous therapies, and treated with lanreotide Autogel 120 mg or placebo.
The primary endpoint is time to either disease progression (using Response
Evaluation Criteria In Solid Tumors) or death. Two baseline computed
tomography scans (�12 weeks apart) are being performed, followed by
additional scans at intervals up to 96 weeks. Secondary endpoints include
proportion of patients alive and without tumor progression at 48 and 96
weeks, time to progression, overall survival, safety, quality of life, plasma
chromogranin A levels, tumor markers, and pharmacokinetic parameters.
The primary study population for the analysis will be the intention-to-treat
population. Recruitment is now complete (n�204) and, thus far, the drug
safety monitoring committee has identified no safety concerns. The trial is
registered with ClinicalTrials.gov (NCT NCT00353496).
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