A Phase I/II, Open-Label, Nonrandomized, Dose-Finding Safety, Tolerance, Pharmacokinetic, and Efficacy Study of Orally Administered S-1 in Combination With Cisplatin in Patients With Advanced Gastric Cancer

Inclusion Criteria

Inclusion Criteria

- Has histologically or cytologically confirmed adenocarcinoma of the stomach or
gastroesophageal junction

- Has advanced, unresectable cancer at the time of study entry

- Has measurable disease as defined by RECIST criteria, i.e., lesions that can be
accurately measured in at least one dimension with the longest diameter ≥20 mm using
conventional techniques or ≥10 mm using spiral CT scan

- Is at least 3 weeks post-gastrectomy surgery

- Has not received prior chemotherapy for their cancer (adjuvant therapy is permitted
and does not count as prior chemotherapy).

- Has performance status of ≥ 70% on the Karnofsky scale (Appendix B)

- Has a predicted life expectancy of ≥ 12 weeks

- Has an absolute granulocyte count of ≥ 1,500/mm3

- Has a platelet count ≥ 100,000/mm3

- Has a hemoglobin of ≥ 9.0 g/dL

- Has a bilirubin of ≤ 1.5 times the ULN

- Has transaminases ≤ 2.5 times the ULN except for patients with liver metastasis who
may have transaminases ≤ 5 times the ULN

- Has a creatinine ≤ ULN and calculated creatinine ≥ 60 mL/min

- According to the judgment of the Investigator, the patient has recovered from all
previous anti-cancer treatment-related toxicities to at least Grade 1 (see exceptions
above)

- Has stopped all previous investigational drugs at least 4 weeks prior to treatment
with S-1 and cisplatin.

- Is able to take medications orally

- Female patients of childbearing potential who are not pregnant and who use acceptable
means of contraception while on study and for an additional 30 days after the last
dose of study medication. Male patients must use adequate contraception.

Exclusion Criteria

- Has relapsed within 6 months from the end of adjuvant therapy

- Has known brain or leptomeningeal metastases.

- Has any other serious illness or medical condition(s) including, but not limited to,
the following:

- uncontrolled congestive heart failure, angina pectoris, arrhythmias, or
hypertension ; or any significant medical condition that is a contraindication
for chemotherapy

- concurrent malignancy other than gastric cancer except adequately treated
carcinoma-in-situ of the cervix or non-melanoma skin cancer

- active infection

- gastrointestinal disorder, including malabsorption, chronic nausea and vomiting,
chronic diarrhea

- unstable diabetes mellitus

- psychiatric disorder that may interfere with consent and/or protocol compliance

- known neuropathy (including hearing loss) at baseline of Grade 2 or higher (as
per NCI CTC v2.0 see Appendix A)

- Has known hypersensitivity to any of the constituents of the study medication

- Is receiving a concomitant treatment with drugs interacting with S-1.

- Is a pregnant or lactating female or who refuses to use an acceptable means of
contraception. Is a male and refuses to use an acceptable means of contraception.