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

Phase 3

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
placebo	placebo	-
apatinib	apatinib	-

Primary Outcome Measures

Name	Time	Method
Progression Free Survival(PFS)	30 months	Progression free survival of All the Evaluable Participants.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of diameters of target lesions, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Overall Survival(OS)	30 months	Overall Survival of the Participants

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate(DCR)	30 months	Disease control is defined as the proportion of patients who had a best response rating of complete response, partial response, or stable disease, and lasted at least 4 weeks.
Objective Response Rate(ORR)	30 months	Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR)
Percentage of Participants With Adverse Events	30 months