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
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
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
- 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
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
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)
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
9. Patients with fresh bleeding from the digestive tract which needs repeated blood
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
15. Pregnant or lactating female.
16. HIV-positive patients.