• To evaluate the progression free survival (PFS) of the combination of bevacizumab, oxaliplatin and capecitabine in patients with previously untreated metastatic esophagogastric adenocarcinoma [ Time Frame: 2+ years from study start date ] [ Designated as safety issue: No ]
  

• To assess the safety and tolerability of the combination of bevacizumab, oxaliplatin and capecitabine in patients with previously untreated metastatic esophagogastric adenocarcinoma [ Time Frame: Every 21 days ] [ Designated as safety issue: Yes ]
  
• To assess response rate (RR) in patients treated with the combination [ Time Frame: Every 9 weeks ] [ Designated as safety issue: No ]
  
• To preliminarily assess overall survival (OS) in patients treated with the combination [ Time Frame: 2 years after study start date ] [ Designated as safety issue: No ]
  
• To evaluate the effect of the combination therapy on blood based biomarkers of angiogenesis. [ Time Frame: Biomarker cycle days 1 and 8 and 15 ] [ Designated as safety issue: No ]
  
• To assess the effect of the bevacizumab monotherapy on tumor and wound angiogenesis, using Immunoblotting, ELISA, and mRNA expression analyses. [ Time Frame: 2 years after study start date ] [ Designated as safety issue: No ]
  

The number of new cases of esophageal and gastric cancers in the United States in 2005 is 14520 for esophageal cancer and 21860 for gastric cancer. Unfortunately, esophageal and gastric cancers will also account for 13570 and 11550 deaths, respectively, in 2005. The 5 year survival rates for metastatic gastroesophageal, GE junctional, and gastric cancers are less than 5%. The major current treatment modality for patients with advanced esophageal, GE junctional, and gastric adenocarcinomas is systemic chemotherapy.

We seek to investigate the efficacy of capecitabine and oxaliplatin in combination with bevacizumab as first line treatment for metastatic esophagogastric cancers. The choice of capecitabine and oxaliplatin is made to develop a user-friendly biologically-based regimen, offering patients oral capecitabine in place of continuous 5FU infusion pumps. Since capecitabine can be given crushed this regimen may both be active and user-friendly. Preliminary data in colorectal cancer suggest that the regimen of capecitabine, oxaliplatin, and bevacizumab has comparable activity to FOLFOX-bevacizumab. The goal of the proposed regimen is to define a capecitabine and oxaliplatin-based regimen that optimizes biological approaches over cytotoxic approaches. The addition of bevacizumab to chemotherapy regimens for metastatic colorectal cancer, metastatic non-small cell lung cancer, and metastatic breast cancer has shown to improve response rates and overall survival. If active, this regimen could serve as a first line comparator to the capecitabine, oxaliplatin, and epirubicin combination. This approach will also help to simplify regimen development across gastrointestinal cancers.

In addition to the primary efficacy endpoint of this protocol, several correlative endpoints will also be examined in an exploratory manner. The importance of developing blood-based and tumor biomarkers has been extensively reviewed. However, the role of such predictive markers has not been well studied for XELOX-A. This information is important since it may help define which populations are most likely to benefit and most likely to suffer significant toxicity from this important GI cancer regimen. This biomarker approach may also help understand and define mechanisms of sensitivity, resistance, and toxicity that may be used to guide future hypothesis-driven studies designed to improve the efficacy and safety of this regimen. The correlative biomarker endpoints include serum, plasma and urine biomarkers (e.g. VEGF and bFGF), a wound healing model of angiogenesis, and tumor biopsy studies .

Inclusion Criteria:

• Histologically documented and radiographically measurable adenocarcinoma of the esophagus or stomach that is metastatic/recurrent and not amenable to potentially curative treatment
• No prior therapy for metastatic disease
• Normal Organ and marrow function

Exclusion Criteria:

• Unstable or poorly controlled hypertension >150/100 mm Hg
• Arterial thromboembolic events within 6 months
• Clinically significant uncontrolled cardiac disease
• Significant proteinuria at baseline.
• Grade 2 or greater peripheral neuropathy
• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months.