A Phase 2 Study of Trastuzumab in Combination With TS-ONE and Cisplatin in Firstline Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
A Phase 2 Study of Trastuzumab in Combination With TS-ONE and Cisplatin in Firstline Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced Gastric Cancer
To explore overall response rate of trastuzumab combined with TS-ONE based chemotherapy in
 first-line HER2-positive advanced gastric cancer.
Inclusion Criteria:

 1. Patients must have histologically or cytologically confirmed adenocarcinoma of the
 stomach and Gastric-esophageal junction.

 2. Patients must have measurable disease, defined as at least one lesion that can be
 accurately measured in at least one dimension (longest diameter to be recorded) as
 more than or equals to 20 mm with conventional techniques or as more than or equals to
 10 mm with spiral CT scan.

 3. Patients without prior systemic treatment. Patients who completed postoperative
 adjuvant chemotherapy (and radiotherapy) more than 180 days before may be enrolled.

 4. Age more than or equals to 21 years.

 5. Life expectancy of greater than 3 months.

 6. ECOG performance status less than or equals to 2 (Karnofsky more than or equals to
 60%).

 7. Patients must have normal organ and marrow function as defined below:

 -  Hemoglobin > 8.0 g/dL

 -  Leukocytes > 3,000/mcL

 -  Absolute neutrophil count > 1,500/mcL

 -  Platelets > 100,000/mcL

 -  Total bilirubin less than or equals to 1.5 X ULN

 -  AST (SGOT)/ALT (SGPT) less than or equals to 3 x institutional upper limit of
 normal

 -  ALP less than or equals to 3 x upper limit of normal*

 -  Creatinine within normal institutional limits OR Creatinine clearance** >60
 mL/min for patients with creatinine levels above institutional normal

 -  In the presence of liver metastasis, patients with AST, ALT and ALP < or = 5
 x the upper limit of normal may be admitted. *In the presence of bone
 metastasis, patients with AST ,ALT and ALP < or = 10x the upper limit of
 normal maybe admitted. **: Creatinine clearance can be estimated using
 Cockcroft-Gault formula man: Ccr (mL/min) = body weight (kg) x (140 -
 age)/(72 x serum creatinine (mg/dL)), woman: Ccr = male Ccr x 0.85]. The
 above CrCl Formula is to be applied in all sites.

 8. Patients who have HER2-positive cancer confirmed with IHC and/or FISH***.

 *** Immunohistochemistry (IHC) for HER-2 is routine as part of pathological evaluation
 of gastric hybridisation (FISH) for Her2 copy number is required. A copy number value
 above 2.2 is taken as positive. The sponsors for the drugs used in our investigator
 initiated trial (Taiho) have kindly agreed to pay for the HER2 FISH test.

 9. Patients able to take orally.

 10. Patients with left ventricular ejection fraction of at least 50% on MUGA or
 2D-echocardiography done within 28 days before enrollment. Should a woman become
 pregnant or suspect she is pregnant while participating in this study, she should
 inform her treating physician immediately.

 11. The effects of proposed regimen on the developing human fetus at the recommended
 therapeutic dose are unknown. For this reason and because antitumor agents as well as
 other therapeutic agents used in this trial are known to be teratogenic, women of
 child-bearing potential and men must agree to use adequate contraception (hormonal or
 barrier method of birth control; abstinence) prior to study entry and for the duration
 of study participation.

 12. Ability to understand and the willingness to sign a written informed consent document.

 13. Consent for fresh frozen tissue collection, mandatory for patients with primary
 in-situ tumors and optional for patients without primary in-situ tumors.

 -  Tissue collection only applicable to National Cancer Centre (S) and National
 University Hospital (S)

 Exclusion Criteria:

 1. Patients who have had radiotherapy within 4 weeks (6 weeks for nitrosoureas or
 mitomycin C) prior to entering the study or those who have not recovered from adverse
 events due to treatment administered more than 4 weeks earlier.

 2. Patients receiving any other investigational agents.

 3. Patients with known brain metastases.

 4. History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to TS-ONE, cisplatin and trastuzumab or other agents used in the study.

 5. Presence of any contraindications to TS-ONE or cisplatin or trastuzumab.

 6. Baseline LVEF (Left Ventricular Ejection Fraction) < 50%.

 7. Patients with serious (e.g.inpatient care is needed) complications (e.g. intestinal
 paralysis, intestinal occlusion, interstitial pneumonia or pulmonary fibrosis,
 poorly-controlled diabetes, renal failure or hepatic cirrhosis).

 8. Patients with massive ascites (moderate or higher, beyond the pelvic cavity and
 retention on the anterior surface of the liver on CT) or massive pleural effusion
 retention.

 9. Patients with fresh bleeding from the digestive tract which needs repeated blood
 transfusion.

 10. Patients with diarrhea (4 or more times per day or watery diarrhea).

 11. Previous malignancy other than gastric cancer diagnosed in the last 5 years except for
 basal cell carcinoma of skin or preinvasive cancer of cervix.

 12. Patients with reproductive potential who refuse to use an adequate means of
 contraception (including male patients).

 13. Significant disease or conditions which, in the investigator's opinion, would exclude
 patient from the study.

 14. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements.

 15. Pregnant or lactating female.

 16. HIV-positive patients.