Overview

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.

Eligibility

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