An Open-label, Single Arm Study to Evaluate the Efficacy and Safety of Trastuzumab in Combination With Capecitabine and Oxaliplatin (XELOX) as a First-line Chemotherapy for Inoperable, Locally Advanced or Recurrent and/or Metastatic Gastric Cancer
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 Tumors
(RECIST 1.0), assessed using imaging techniques (CT or MRI).
3. HER2 positive tumour (primary tumour or metastasis) as assessed by the central
laboratory. (Both IHC and Dual SISH will be performed on all patients in the central
4. ECOG Performance status 0, 1 or 2.
5. Life expectancy of at least 3 months.
6. Male or female. Age ≥ 18 years.
7. Signed informed consent.
1. Previous chemotherapy for advanced/metastatic disease (prior adjuvant/neoadjuvant
therapy is allowed if at least 6 months has elapsed between completion of
adjuvant/neoadjuvant therapy and enrolment into the study; the total dose of
cisplatin should be less than 300mg/m2, adjuvant/neoadjuvant therapy with oxaplatin
is not allowed).
2. No prior use of EGFR-targeting drugs,such as Trastuzumab,lapatinib or other TKIs.
3. Lack of physical integrity of the upper gastrointestinal tract or malabsorption
syndrome (e.g. patients with partial or total gastrectomy can enter the study, but
not those with a jejunostomy probe).
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 4.0.
6. Other malignancy within the last 5 years, except for carcinoma in situ of the cervix,
or basal cell carcinoma.
7. Neutrophil count < 1.5 × 109/L, or hemoglobin < 90 g/L,or platelet count < 100 ×
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. Creatinine clearance < 60 mL/min.
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. Baseline LVEF < 50% (measured by echocardiography or MUGA).
12. Patients with dyspnoea at rest due to complications of advanced malignancy or other
disease, or who require supportive oxygen therapy.
13. 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
14. Clinically significant hearing abnormality.
15. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
16. History or clinical evidence of brain metastases.
17. Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly
18. Positive serum pregnancy test in women of childbearing potential.
19. Subjects with reproductive potential not willing to use an effective method of
20. Received any investigational drug treatment within 4 weeks of start of study
21. 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;prior adjuvant radiotherapy is allowed if complete
at least 6 months ).
22. Major surgery within 4 weeks of start of study treatment, without complete recovery.
23. Patients with known active infection with HIV, HBV, or HCV.
24. Known hypersensitivity to any of the study drugs.