Dose Finding and Pharmacokinetics/Pharmacodynamics Study of Apatinib in the Treatment of Advanced Colorectal Cancer

Inclusion Criteria: * ≥ 18 and ≤ 70 years of age * Histological confirmed advanced or metastatic colorectal Cancer，at least one measurable lesion, larger than 10 mm in diameter by spiral CT scan(scanning layer ≤ 5 mm ) * Have failed for ≥ 2 lines of chemotherapy * Life expectancy of more than 3 months * ECOG performance scale ≤ 1 * Duration from the last therapy is more than 6 weeks for nitroso or mitomycin More than 4 weeks for operation, radiotherapy or cytotoxic agents * Adequate hepatic, renal, heart, and hematologic functions (platelets \> 80 × 10E+9/L, neutrophil \> 1.5 × 10E+9/L, serum creatinine ≤ 1×upper limit of normal(ULN), bilirubin \< 1.25 ULN, and serum transaminase ≤ 2.5× ULN) * Child bearing potential, a negative urine or serum pregnancy test result before initiating apatinib, must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. * Signed and dated informed consent. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. Exclusion Criteria: * History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix * Pregnant or lactating women * Preexisting uncontrolled hypertension defined as more than 140/90 mmHg despite using single medical therapy, more than class I (NCI CTCAE 3.0 ) myocardial ischemia, arrhythmia(including QTcF:male ≥ 450 ms, female ≥ 470 ms), or cardiac insufficiency myocardial ischemia, arrhythmia, or cardiac insufficiency * Before or at the same time any, second malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix * Any factors that influence the usage of oral administration Evidence of CNS metastasis * URT: urine protein ≥ (++)and \> 1.0 g of 24 h * PT, APTT, TT, Fbg abnormal, having hemorrhagic tendency (eg. active peptic ulcer disease) or receiving the therapy of thrombolysis or anticoagulation * Abuse of drugs * Certain possibility of gastric or intestine hemorrhage * Less than 4 weeks from the last clinical trial * Viral hepatitis type B or type C * Prior VEGFR inhibitor treatment * Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study