Phase II Study of Oxaliplatin, Capecitabine and Endostar as First Line Treatment for Patients With Advanced Colorectal Cancer
Among the different combination regimens of new drugs in CRC treatment, the combination of
capecitabine and oxaliplatin seems especially attractive. Both drugs have a different and
relatively mild toxicity profile. In phase II studies that used the recommended dose of
XELOX (capecitabine 1000 mg/m2 twice daily on days 1-14 with intravenous oxaliplatin 130
mg/m2 on day 1 every 3 weeks), RRs were between 42% and 55%, with PFS times of 6.0 to 7.7
months, which showed that the XELOX combination was effective in the first-line treatment of
patients with metastatic CRC. (Cassidy et al, 2004; Scheithauer et al, 2003)
Colorectal carcinomas (CRC) are characterised by enhanced VEGF expression and the
corresponding high microvascular densities, indicating increased angiogenic activity and
leading to worse patient survival.(Zheng et al, 2003; Des Guetz et al, 2006) Recently, the
final results of XELOX-1/NO16966, a study of first line therapy, confirmed that
bevacizumab+chemotherapy (XELOX or FOLFOX) was superior to chemotherapy alone in terms of
PFS (HR 0.83; p=0.0023) although the OS data did not reach statistical significance (HR
0.89; p=0.0769). (Saltz et al, 2008)
The bevacizumab data provide a treatment option for patients with metastatic CRC based on
VEGF inhibition. It is hypothesized that other anti-angiogenic agents such as endostar, may
augment the effect of chemotherapy regimens in CRC. Endostar, a recombinant human endostatin
which expressed and purified in E. coli, was approved by the SFDA for the treatment of
non-small-cell lung cancer in 2005. Ling et al. found that endostar suppressed the
VEGF-stimulated proliferation, migration, and tube formation of human umbilical vein
endothelial cells (HUVECs) in vitro, and the antiangiogenic effects of endostar were
correlated with the VEGF-triggered signaling. (Ling et al, 2007) A Chinese phase III
clinical trial in advanced non-small-cell lung cancer, endostar--a new angiogenesis
inhibitor prolonged the overall survival, time to progression and improved response rate.
(Wang et al, 2005) Based on these results, we design this phase II clinical trial of
oxaliplatin, capecitabine and endostar as first line treatment, to evaluate whether endostar
can bring survival benefits to patients with advanced colorectal cancer.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to progression
6 months
Yes
Weiguo Cao, MD
Study Chair
Department of Oncology, Ruijin Hospital, Medical School of Shanghai Jiaotong University
China: Food and Drug Administration
200902024
NCT00853684
February 2009
March 2011
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