Capecitabine and Cisplatin (XP)+Sorafenib in Advanced Gastric Cancer (AGC): Sorafenib+XP

A Phase I-II Study of Sorafenib (Nexavar®) in Combination With Capecitabine and Cisplatin (XP) in Patients With Advanced Gastric Cancer

There is strong scientific rationale for exploring the role of sorafenib with capecitabine and cisplatin (XP) in AGC. XP is a new standard of care in AGC and sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2 and PDGFR-beta.

Inclusion Criteria:

• Having given signed written informed consent
• Unresectable advanced gastric adenocarcinoma, initially diagnosed or recurred
• No history of chemotherapy or radiation
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
• Age 18-75 years
• Estimated life expectancy of more than 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Adequate bone marrow function (absolute neutrophil count > 1,500/µL, platelets > 100,000/µL, hemoglobin > 8g/dl),
• Adequate kidney function (creatinine clearance > 60 ml/min)
• Adequate liver function (bilirubin < 2.0 mg/dL, transaminases levels < 3 times the upper normal limit [5 times for patients with liver metastasis])

Exclusion Criteria:

• Past or concurrent history of neoplasm other than gastric adenocarcinoma, except for curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix uteri
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start
• Presence of central nervous system metastasis
• Obvious peritoneal seeding or bowel obstruction
• Evidence of serious gastrointestinal bleeding
• Peripheral neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Event version 3.0 > Grade I)
• History of significant neurologic or psychiatric disorders
• Pregnant or lactating women, women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions
• Known allergy to study drugs