Ph II of Capecitabine, Carboplatin & Bevacizumab for Gastroesophageal Junction & Gastric Carcinoma

Inclusion Criteria:

Subjects must be treated at Stanford University Medical Center for the entire length of study participation.

1. Patients with histologically or cytologically confirmed adenocarcinoma of the GEJ or stomach.
2. Patients must be deemed unresectable due to involvement of critical vasculature or adjacent organ invasion. If unresectable, patients must show evidence of disease progression prior to enrollment.
3. Patients with prior surgical resection who develop radiological or clinical evidence of metastatic cancer do not require separate histological or cytological confirmation of metastatic disease unless an interval of \> 5 years has elapsed between the primary surgery and the development of metastatic disease. Clinicians should consider biopsy of lesions to establish diagnosis of metastatic disease if there is substantial clinical ambiguity regarding the nature or source of apparent metastases.
4. Prior carboplatin as neoadjuvant or adjuvant therapy will be allowed if \>= 6 months from the time of study entry.
5. If patients use aspirin (\>325mg/day) or NSAIDS at the time of enrollment, they must have a 10 day washout period prior to beginning protocol treatment.
6. Low molecular weight heparin (or its equivalent, excluding warfarin) will be allowed for treatment of venous thromboembolic events if patients have no evidence of bleeding on full-dose anticoagulation.
7. Patients must have a primary or metastatic lesion measurable in at least one dimension by Modified RECIST criteria (see Section 11.2.3) within 4 weeks prior to entry of study
8. Patients must have ECOG performance status of 0-1
9. Patients must be \>= 18 years of age
10. Laboratory values \<= 2 weeks prior to randomization:

    * Absolute Neutrophil Count (ANC) \>= 1.5 x 109/L (\>= 1500/mm3)
    * Platelets (PLT) \>= 100 x 109/L (\>= 100,000/mm3)
    * Hemoglobin (Hgb) \>= 9 g/dL
    * Serum creatinine \<= 1.5 x ULN
    * Serum bilirubin \<= 1.5 x ULN (\<= 3.0 x ULN if liver metastases present)
    * Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) \<= 3.0 x ULN (\<= 5.0 x ULN if liver metastases present). Note: ERCP or percutaneous stenting may be used to normalize the liver function tests.
11. Life expectancy \>= 12 weeks
12. Inclusion and exclusion criteria for DCE-MRI and DWI imaging will be determined by CT scan as part of routine post-chemotherapy imaging. Subjects will be eligible if one liver metastasis is greater than 1 cm in size. Participation in the DCE-MRI and DWI correlate is not required for eligibility.
13. Ability to give written informed consent according to local guidelines

Exclusion Criteria:

1. Disease-Specific Exclusions

   1. Prior chemotherapy for metastatic disease
   2. Prior full field radiotherapy \<= 4 weeks or limited field radiotherapy \<= 2 weeks prior to enrollment. Patients must have recovered from all therapy-related toxicities. The site of previous radiotherapy should have evidence of progressive disease if this is the only site of disease.
   3. Prior biologic or immunotherapy \<= 2 weeks prior to registration. Patients must have recovered from all therapy-related toxicities
   4. Prior therapy with anti-VEGF agents
   5. If history of other primary cancer, subject eligible only if she or he has:

      * Curatively resected non-melanomatous skin cancer
      * Curatively treated cervical carcinoma in situ
      * Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years
   6. Concurrent use of other investigational agents and patients who have received investigational drugs \<= 4 weeks prior to enrollment.
   7. Hypersensitivity to capecitabine, fluorouracil, or any component of the formulation and or a known deficiency of dihydropyrimidine dehydrogenase.
2. General Medical Exclusions

   1. Subjects known to have chronic or active hepatitis B or C infection
   2. History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with study participation or study drug administration or may interfere with the conduct of the study or interpretation of study results
   3. Male subject who is not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of second-line treatment
   4. Female subject (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) who is not willing to use an oral, patch or implanted contraceptive, double-barrier birth control, or an IUD during the course of the study and for 6 months following the last dose of second-line treatment
   5. Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
   6. Pleural effusion or ascites that causes respiratory compromise (\>= CTCAE grade 2 dyspnea)
   7. Any of the following concurrent severe and/or uncontrolled medical conditions within 24 weeks of enrollment which could compromise participation in the study:

      * Unstable angina pectoris
      * Symptomatic congestive heart failure
      * Myocardial infarction \<= 6 months prior to registration and/or randomization
      * Serious uncontrolled cardiac arrhythmia
      * Uncontrolled diabetes
      * Active or uncontrolled infection
      * Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung.
      * Chronic renal disease
      * Acute or chronic liver disease (e.g., hepatitis, cirrhosis)
   8. Patients unwilling to or unable to comply with the protocol
   9. Life expectancy of less than 12 weeks
   10. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study
3. Bevacizumab-Specific Exclusions

   1. Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
   2. Any prior history of hypertensive crisis or hypertensive encephalopathy
   3. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix A)
   4. History of myocardial infarction or unstable angina within 6 months prior to study enrollment
   5. History of stroke or transient ischemic attack within 6 months prior to study enrollment
   6. Known CNS disease, brain metastases.
   7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
   8. Symptomatic peripheral vascular disease
   9. Evidence of bleeding diathesis or coagulopathy
   10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
   11. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
   12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
   13. Serious, non-healing wound, ulcer, or bone fracture
   14. Urine protein \>= 2+ on urinalysis dipstick and \>= 1.0 gram on 24-hour urine collection
   15. Known hypersensitivity to any component of bevacizumab
   16. History of hemoptysis (bright red blood of ½ teaspoon or more per episode) within 3 months prior to study enrollment.
   17. Current, ongoing treatment with full-dose warfarin.