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

Study Overview
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Brief Summary
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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.

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

Conditions
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Advanced or Metastatic Gastric Cancer

Intervention / Treatment
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* Drug: apatinib
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: apatinib<br> | Drug: apatinib<br>* apatinib 850 mg qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* placebo qd p.o. until disease progression or intolerable toxicity or patients withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) | 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). | 30 months | 
| Overall Survival(OS) | Overall Survival of the Participants | 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate(DCR) | 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. | 30 months | 
| Objective Response Rate(ORR) | Objective Response Rate is defined as the proportion of patients with complete response(CR) or partial response(PR) | 30 months | 
| Percentage of Participants With Adverse Events |  | 30 months |