Clinical trial: 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 (NCT01736410)

Eligibility criteria:
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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 21 Years old.


Patient description (medical language): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient description (patient's own words): I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Does the patient match the trial criteria? 1