Intraperitoneal Paclitaxel With XELOX in Gastric Cancer With Peritoneal Metastasis

Phase I,II Study of First Line Intraperitoneal Paclitaxel With Systemic Capecitabine and Oxaliplatin Combination Therapy in Patients With Advanced Gastric Cancer With Peritoneal Metastasis

IPXELOX will investigate the safety, tolerability, and antitumor activity of intraperitoneal paclitaxel in combination with chemotherapy in patients with advanced gastric cancer with peritoneal metastasis.

Study hypotheses: Intraperitoneal paclitaxel administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and anti-tumor efficacy with systemic capecitabine and oxaliplatin in advanced gastric cancer with peritoneal metastasis.

1. Inclusion Criteria:

   • ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1
   • pathologically proven primary gastric adenocarcinoma
   • peritoneal metastasis confirmed by laparoscopy or diagnostic imaging
   • written informed consent
   • adequate function of important organs (within 14 days before registration)

   Absolute neutrophil count ≥1.5 x 10^9/L, Platelet >=100,000/mm3, Hemoglobin >=8.0g/dL, Total bilirubin <= ≤ 2.0mg/dl or ULN(Upper Limit of Normal) x 1.5, AST(aspartate aminotransferase) <=100IU/L(International Unit/Liter), ALT(alanine transaminase) <=100IU/L, Creatinine clearance ≥ 50mL/min (milliliter/minute),

2. Exclusion Criteria:

   • other active concomitant malignancies
   • HER2(human epidermal growth factor receptor 2) positive (Immunohistochemistry 3+ or 2+ with in situ hybridization positive)
   • no investigational anticancer therapy within 30 days prior to the first dose of study treatment
   • recent (within 6 months) acute coronary syndrome, severe heart failure or severe pulmonary disease
   • uncontrolled acute or chronic disease
   • uncontrolled infection or inflammation
   • uncontrolled psychiatric disorder or central neurologic disease
   • not fully recovered from previous surgery
   • prior anticancer therapy (chemotherapy, immunotherapy, radiation) within 6 months
   • intolerable to oral administration or a lack of physical integration of the upper gastrointestinal tract or with a malabsorption syndrome
   • fertile males and females who are unwilling to use effective contraceptive methods.
   • pregnancy, breast feeding or intention to become pregnant
   • interstitial pneumonia or pulmonary fibrosis
   • peripheral neuropathy with functional impairment
   • hypersensitivity to paclitaxel, oxaliplatin, capecitabine, fluoropyrimidine or Cremophor EL.
   • concomitant therapy with any substrate or inhibitor of Cytochrome P450 2C8 or 3A4
   • concomitant therapy with sorivudine or brivudine
   • Dihydropyrimidine dehydrogenase (DPD) deficiency.
   • current or recent (within the 7 days prior to enrollment) treatment of tegafur-gimeracil-oteracil potassium