30 patients with advanced melanoma will receive apatinib plus Temozolomide as maintenance therapy.

In this study, we plan to enroll 30 patients with advanced melanoma patients who have failed at least one systemic treatment regimen. The therapeutic regimen is temozolomide, 300mg,po, d1-5, apatinib, 500 mg, qd, po, d1-28, Every 28 days for 1 cycles, the primary end point was PFS, the secondary end point was OS, DCR, ORR etc. So we plan to investigate the safety and efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients.

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.