['melanoma']
['palbociclib']

        Inclusion Criteria:

          1. Age from 18 to 75 years;

          2. ECOG performance status 0 or 1 before treatment;

          3. Metastatic melanoma or unresectable acral melanoma;

          4. Histologically confirmed melanoma.

          5. Bearing gene aberrations in cell cycle pathways [including CDK4 amplification and/or
             CCND1 amplification and/or P16 (CDKN2A) loss].;

          6. Anticipated life expectancy ≥ 3 month;

          7. Adequate organ function, defined as following criteria:

               1. Platelets 75 x 109/L, Hemoglobin 9.0 g/dL, Absolute Neutrophils(ANC) ≥ 1.5x109/L;

               2. Serum bilirubin ≤ 1.5*upper limit of normal (ULN) (could be ignored in the case
                  of Gilbert's syndrome) ，Serum aspartate transaminase (AST) and serum alanine
                  transaminase (ALT) ≤ 1.5 * ULN;

               3. Blood urea nitrogen (BUN) ≤ 1.5 * ULN, serum creatinine (Cr) ≤ 1.5 * ULN.

               4. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as
                  assessed by multigated acquisition (MUGA) scan or echocardiography;

               5. QTc interval: male < 450msec, female < 470msec (via Fridericia method)

          8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory
             tests, and other study procedures.

          9. Written informed consent signed.

        Exclusion Criteria:

          1. Previous or current administration of any kind of CDK4/6 inhibitors;

          2. Administration of any other anti-tumor therapy (including but not limited to
             radiotherapy, chemotherapy, endocrinal therapy, surgery, molecular targeted therapy,
             immunotherapy or biological therapy) 4 weeks before inclusion; administration of
             mitocycin or nitrosamines 8 weeks before inclusion;

          3. Non-treated brain metastasis (treatment controlled stable brain metastasis judged by
             investigators excluded);

          4. Presence of third space fluid that cannot be controlled by drainage or other means
             (i.e. pleural effusion or ascites);

          5. Long-term steroid therapy required;

          6. Uncorrectable hypokalemia or hypomagnesaemia before inclusion;

          7. Concurrent administration of drugs with potential of QT interval prolongation (such as
             antiarrhythmic drugs);

          8. Allergies or previous history of severe allergies;

          9. Active HBV or HCV infection (HBV viral copy number ≥ 104 copies/ml, HCV ≥ 103
             copies/ml);

         10. NCICTCAE Grade 2 toxicity before inclusion;

         11. Diagnosed as any second primary malignant tumor in 5 years before inclusion;

         12. Following conditions occur in the 6 months before drug administration: severe/
             unstable angina pectoris, myocardial infarction, congestive heart failure with
             symptoms, cerebrovascular accident, including transient ischemic attack, pulmonary
             embolism, ≥ grade II renal dysfunction, and other severe diseases that investigators
             judged to be unsuitable for this trial;

         13. Administration of potent CYP3A4 inhibitors in 7 days before inclusion , or
             administration of potent CYP3A4 inhibitors in 12 days before randomization ；

         14. NCICTCAE Grade ≥ 2 Active arrhythmias;

         15. Hypertension, defined as systolic blood pressure >150mmHg and/or diastolic blood
             pressure >100mmHg，and cannot be controlled by medication;

         16. No recommendation to receive >2 mg Warfarin treatment in 2 weeks before study
             beginning. It is permitted to use low dose Warfarin(<2 mg／3day) to prevent deep venous
             thrombosis. Low molecular weight heparin (fractionated) or aspirin are also allowed;

         17. Existence of any disease affecting drug absorption, including but not limited to: no
             ability to swallow oral medications, active inflammatory bowel disease, partial or
             complete obstruction, partial or total gastrectomy, extensive bowel resection or
             chronic diarrhea;

         18. Known infection of human immunodeficiency virus (HIV) or acquired immunodeficiency
             syndrome (AIDS)-related illness, or congenital immune deficiency diseases, organ
             transplantation history;

         19. Pregnancy, breastfeeding, childbearing age female who is reluctant to take effective
             contraceptive measures throughout trial period. All female patients with reproductive
             potential must have a negative pregnancy test (serum or urine) within 7 days before
             randomization and at first day of every cycle on visit.

         20. Other severe acute or chronic physiological or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the patient inappropriate for entry into
             this study.

         21. Current treatment on another clinical trial. Supportive care or non-therapeutic
             clinical trials are allowed.
      