Docetaxel, Oxaliplatin, Capecitabine, Bevacizumab and Trastuzumab in Patients With Locally Advanced or Metastatic Gastric Cancer

Inclusion Criteria: 1. Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable locally advanced or recurrent and/or metastatic disease not amenable to curative therapy. 2. Measurable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST), assessed using imaging techniques (CT or MRI) 3. ECOG Performance status 0, 1 or 2 (see Appendix 2) 4. Life expectancy of at least 3 months 5. Male or female age ≥ 18 years. 6. Signed informed consent. 7. Assessment of HER2 status (primary tumour or metastasis) by the central laboratory prior to initiation of study treatment (see section 9.1) 8. Able to swallow and retain oral medication. 9. LVEF ≥ 50% assessed by multigated radionucleotide angiography (MUGA) or cardiac ultrasound. Exclusion Criteria: Any of the following will exclude the patient from the study: 1. Previous chemotherapy for advanced/metastatic disease (prior peri-operative chemotherapy is allowed if at least 6 months has elapsed between completion of this therapy and enrolment into the study). 2. Previous radiotherapy on the abdomen. 3. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma. 4. Patients with active (significant or uncontrolled) gastrointestinal bleeding. 5. Residual relevant toxicity resulting from previous therapy (with the exception of alopecia), e.g. neurological toxicity ≥ grade 2 NCI-CTCAE. 6. Creatinin clearance \<50 mL/min. 7. Neutrophil count \<1.5 × 109/L, or platelet count \<100 × 109/L. 8. Serum bilirubin \>1.5 × upper limit of normal (ULN); or, AST or ALT \>2.5 × ULN (or \>5 × ULN in patients with liver metastases); or, alkaline phosphatase \>2.5 × ULN (or \>5 × ULN in patients with liver metastases, or \>10 × ULN in patients with bone but no liver metastases); or, albumin \<25 g/L. 9. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 10. History of documented congestive heart failure; angina pectoris requiring medication; evidence of transmural myocardial infarction on ECG; poorly controlled hypertension (systolic BP \>180 mmHg or diastolic BP \>100 mmHg); clinically significant valvular heart disease; or high risk uncontrollable arrhythmias. 11. Patients with dyspnoea at rest due to complications of advanced malignancy or other disease, or who require supportive oxygen therapy. 12. Patients receiving chronic or high dose corticosteroid therapy. (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed). 13. Major surgery within 4 weeks of start of study treatment; serious or not healing wound. 14. Known hypersensitivity to any of the study drugs, Chinese hamster ovary cell products or other murine or human recombinant antibodies. 15. History or clinical evidence of brain metastases. 16. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes. 17. Positive serum pregnancy test in women of childbearing potential. 18. Subjects with reproductive potential not willing to use an effective method of contraception. 19. Any investigational drug treatment within 4 weeks of start of study treatment. 20. Radiotherapy within 4 weeks of start of study treatment (2 week interval allowed if palliative radiotherapy given to bone metastastic site peripherally and patient recovered from any acute toxicity) 21. Arterial thrombosis; cerebrovascular accident within 6 months prior to study enrolment. 22. Therapeutic use of oral coumarin-derived or LMWH anticoagulants or NSAIDs. 23. Continuous use of immunosuppressive agents (for the use of corticosteroids see also #12).