A Study of Apatinib Combined With Temozolomide in Patients Witn Advanced Melanoma

Inclusion Criteria:

* Age 18-70 years old；
* ECOG performance scale 0-1；
* Life expectancy of more than 3 months；
* Histologically or cytologic confirmed melanoma；
* Temozolomide has not been previously treated；
* Patients who have failed at least one systemic treatment regimen： including but not limited to patients receiving immunotherapeutics such as PD-1 monoclonal antibodies, PDL-1 monoclonal antibodies, ipilimumab, C-kit inhibitors, Braf inhibitors, and molecular targeted drugs.
* For results of blood routine test and biochemical tests： Hgb\>100g/L, ANC\>2.0×109/L, PLT\>100×109/L, Serum Total bilirubin ≤ 1.5 X UNL, ALT and AST ≤ 2.5 x upper normal limit (UNL), and ≤ 5 x UNL（Hematogenous metastases）, Serum Creatine ≤ 1.5 x UNL；
* Informed consent；
* Willingness and ability to comply with scheduled visits.

Exclusion Criteria:

* 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)；
* With ≥grade 2 coronary heart disease, arrhythmia (including QTc interval prolongation male ≥450 ms, women ≥470 ms)；
* Imaging studies have shown that the tumor has been infringing on an important perivascular or when the researcher determines that the patient's tumor has a high risk of fatal hemorrhage during treatment；
* Abnormal Coagulation (INR\>1.5, PT\>UNL+4 seconds), with tendency of bleed or receiving the therapy of thrombolysis or anticoagulation.；
* Urine protein ≥++ or confirmed \>1.0 g by the 24h quantity；
* Pregnant and lactating women, or female patients of child-bearing age without taking contraceptive measures；
* A history of psychotropic substance abuse and can not be abstinent or mental disorders ；
* There are serious concomitant diseases that endanger patient safety or affect the patient in completing the study；
* Patients participating in other clinical trials simultaneously；
* Other situations that the researchers considered unsuitable for this study；
* Confirmed brain metastasis.