Phase II Study of Docetaxel, Oxaliplatin, Capecitabine With Bevacizumab and Trastuzumab in Case of Human Epidermal Growth Factor Receptor 2 (HER2)-Positivity in Patients With Locally Advanced or Metastatic Gastric Cancer or Adenocarcinoma of the Gastro-oesophageal Junction (B-DOCT Study)
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
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
13. Major surgery within 4 weeks of start of study treatment; serious or not healing
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
17. Positive serum pregnancy test in women of childbearing potential.
18. Subjects with reproductive potential not willing to use an effective method of
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
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