RATIONALE:

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.

PURPOSE:

1. Studying how well Apatinib works in treating patients.
2. Finding the efficacy and safety of 500 mg or 750mg Apatinib.
3. Pharmacokinetics/Pharmacodynamics(PK/PD).
4. Exploring new outcome measures of antiangiogenic drugs.

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