Trial Information

Neoadjuvant Chemoradiation Therapy With Oxaliplatin and Capecitabine for Patients With Surgically Resectable Gastric Cancer: A Pilot Phase II Trial With Molecular Correlates

OBJECTIVES:

- Determine the pathologic complete response rate in patients with primary gastric
adenocarcinoma treated with neoadjuvant chemoradiotherapy comprising oxaliplatin,
capecitabine, and radiotherapy. (This will not be completed as this study was closed
early due to poor accrual.)

- Assess the frequency and severity of toxicities associated with this regimen.

- Explore, preliminarily, the association between DNA repair genes (ERCC-1, XRCC1,
GST-P1, XPD, XPA, ribonucleotide reductase), target enzymes (thymidylate synthase [TS],
dihydropyrimidine dehydrogenase, thymidine phosphorylase [TP]), and angiogenic factors
(vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], PD-ECGF,
basic fibroblast growth factor, TSP-1 and -2, transforming growth factor [TGF]-β, and
IL-8) and response to neoadjuvant therapy in patients with adenocarcinoma of the
stomach. (This will not be completed as this study was closed early due to poor
accrual.)

- Explore, preliminarily, the association of haplotypes of candidate genes of TS, TP,
ERCC-1, XPD, GST-P1, cyclooxygenase-2, EGF receptor, TGF-β, VEGF, and IL-8 with
response and toxicity to neoadjuvant chemoradiation therapy in these patients. (This
will not be completed as this study was closed early due to poor accrual.)

- Explore, preliminarily, the feasibility of performing comparative genomic hybridization
for analysis of DNA copy number changes in predicting response to neoadjuvant
chemoradiation therapy. (This will not be completed as this study was closed early due
to poor accrual.)

OUTLINE: This is a multicenter, pilot study.

- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1 and 22
and oral capecitabine twice daily on days 1-14 and 22-35 in the absence of disease
progression or unacceptable toxicity.

- Neoadjuvant chemoradiotherapy: Patients receive oral capecitabine twice daily on days
43-77 and undergo radiotherapy once daily on days 43-47, 50-54, 57-61, 64-68, and 71-75
in the absence of disease progression or unacceptable toxicity.

- Surgery: Patients with stable or responding disease undergo surgery 4-6 weeks after
completion of chemoradiotherapy.

Tumor tissue is obtained at surgery or endoscopic biopsy. Gene expression analysis and
comparative genomic hybridization testing are conducted on the tissue. Blood is drawn prior
to beginning study treatment and is analyzed for germline polymorphisms.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.