Phase III Study of Apatinib Tablets in the Treatment of Advanced or Metastatic Gastric Cancer

A Randomized, Double Blinded, Placebo Controlled Multicenter Phase III Study of Apatinib Mesylate Tablets in the Treatment of Advanced or Metastatic Gastric Cancer

Apatinib is a tyrosin-inhibitor agent targeting at vascular endothelial growth factor receptor (VEGFR), and it's anti-angiogenesis effect has been viewed in preclinical tests. The investigators' phase I study has shown that the drug's toxicity is manageable and the maximum tolerable daily dose is 850 mg. The purpose of this study is to determine whether apatinib can improve progression free survival or overall survival compared with placebo in patients with metastatic gastric carcinoma who failed two lines of chemotherapy.

Inclusion Criteria:

• ≥ 18 and ≤ 70 years of age
• Histological confirmed advanced or metastatic adenocarcinoma of the stomach
• Have failed for at least 2 lines of chemotherapy
• Life expectancy of at least 12 weeks.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1 within 1 week before randomization.
• At least one measurable lesion beyond stomach (larger than 10 mm in diameter by spiral CT scan)
• Duration from the last therapy is more than 6 weeks for nitroso or mitomycin
• More than 4 weeks for operation or radiotherapy
• More than 4 weeks for cytotoxic agents or growth inhibitors
• Adequate hepatic, renal, heart, and hematologic functions (HB ≥ 90g/L,platelets > 80 ×10 E+9/L, neutrophil > 1.5 × 10 E+9/L, serum creatinine ≤ 1× upper limit of normal(ULN), bilirubin < 1.25× ULN, and serum transaminase ≤ 2.5× ULN).

Exclusion Criteria:

• Pregnant or lactating women
• History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg).
• Any factors that influence the usage of oral administration; Evidence of Central Nerves System(CNS) metastasis
• Intercurrence with one of the following: coronary artery disease, arrhythmia ,heart failure and proteinuria ≥ (+)
• International Normalize Ratio (INR) > 1.5 and activated partial thromboplastin time（APPT） > 1.5 × ULN
• Abuse of alcohol or drugs
• Certain possibility of gastric or intestine hemorrhage
• Less than 4 weeks from the last clinical trial
• Prior VEGFR inhibitor treatment
• Disability of serious uncontrolled intercurrence infection Objective evidence of previous or current pulmonary fibrosis history, interstitial pneumonia, Pneumoconiosis, radiation pneumonitis, drug-related pneumonia, Pulmonary function damaged seriously etc.