Irinotecan/Cisplatin, Potentially Curative Surgery With or Without Floxuridine, Followed by Capecitabine for Stomach and Gastro-esophageal Junction (GEJ) Cancers

A previous Phase-II trial conducted by the same principle investigator(s), utilizing
preoperative chemotherapy and intraperitoneal consolidation, was conducted in patients with
locally advanced, potentially resectable gastric cancer or cancer of the gastro-esophageal
junction (GEJ), both staged as T3N0, T4N0, any TN1 or TN2 disease. The data suggest that for
patients with locally advanced gastric or GEJ cancer, systemic induction therapy, curative
surgery with high Ro resection rates, and IP adjuvant therapy, has acceptable toxicity and
encouraging survival outcome. The Medical Research Council Adjuvant Gastric Infusional
Chemotherapy (MAGIC) trial has also shown that perioperative chemotherapy - chemotherapy
given both before and after surgery - can provide a significant survival benefit.

The investigators hypothesize that adjuvant intraperitoneal salvage of cancer micrometastatic
residues after surgery contributes to disease-free survival. The goal of this trial is to
determine whether IP Floxuridine, added to adjuvant postoperative chemotherapy, prolongs
patient's survival. This will be tested during the randomized open-label trial.

- Only untreated patients with histologically documented gastric/GEJ adenocarcinoma,
clinical American Joint Committee on Cancer (AJCC) stage grouping (11) IB-IV (Mo) by
CT scan and laparoscopy/endoscopic ultrasound, are eligible. Excluded are patients in
need of urgent surgery for gastro-intestinal obstruction, perforation or hemorrhage.

- Both men and women >= 18 years of age with Eastern Cooperative Oncology Group (ECOG)
performance status 0-2, members of any ethnic group and minorities.

- Patients without another invasive malignancy, with adequately treated basal cell or
squamous cell skin cancer, free for 5 years or more of in-situ cervix cancer or other
in-situ cancer.

- Since immune deficiency increases the risk of terminal infections when aggravated by
bone marrow suppressive therapy, patients must be without active or uncontrolled
infection including HIV.

- Patients without psychiatric disorders that may interfere with their consent and/or
with protocol follow-up.

- An adequate bone-marrow reserve (absolute neutrophil count >= 1,500/ mmL, thrombocytes
>= 100,000 mmL, hemoglobin >= 9 gm/dL).

- Preserved liver and renal function (total serum bilirubin <2 mg/dL, SGOT/SGPT =< 3x
the upper limit of normal, alkaline phosphatase =< 3x the upper limit of normal, blood
urea nitrogen (BUN) =< 30 mg/dL, serum creatinine concentration <1.5 mg/dL and
creatinine clearance >= 50 mL/min) are required. Creatinine clearance should be
normalized for 1.73 M^2 BSA. The prothrombin time, activated partial thromboplastin
time, and thrombin time should be within the range of normal values.

- Since chemotherapeutic agents to be used are known or suspected to be teratogenic or
with other adverse effects, women must not be pregnant or breast-feeding. All females
of childbearing potential must have a blood test or urine study within 2 weeks prior
to registration to rule out pregnancy. All patients of reproductive age may not
participate unless they agree to use an effective medically acceptable contraceptive
method.

- Patients without diagnosed Gilbert's disease and bilirubin level >= 2.0 mg/dL, as
these patients may have excessive CPT-11 toxicity.

- No prior severe reaction to fluoropyrimidine therapy or known hypersensitivity to
5-fluorouracil. Capecitabine (Xeloda) is contraindicated in patients with severe renal
impairment, i.e., creatinine clearance below 30 mL/min, determined by Cockcroft-Gault
equation shown on page 15 under (i) Renal impairment. In patients with moderate renal
impairment (creatinine clearance 30-50 mL/min), which develops during the course of
adjuvant treatment with Capecitabine, the drug is decreased to 75% of the starting
dose.

- Patients should be without any severe concurrent disease, such as cardiac condition
not responding to medication, myocardial infarction within the last 12 months, active
infection or uncontrolled pulmonary disease, or any other disease which in judgment of
the investigator would make the patient inappropriate for entry into this study.

- Patients who signed written informed consent.