Dose Escalation and PK Study of M2ES in Subjects With Advanced Solid Tumors

• Pharmacokinetic (PK) behavior of M2ES in tumor subject [ Time Frame: 4 week ] [ Designated as safety issue: Yes ]
  Pharmacokinetic (PK) behavior of different doses of M2ES in Subjects With Advanced Solid Tumors
• The incidence rate of adverse event [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  The incidence rate of adverse event

This study is dose-escalation open-label study to determine the MTD of M2ES in Subjects With Advanced Solid Tumors the recommended Phase II dose.The recommended dose and regimen of M2ES will be selected to perform the pharmacokinetic study profiles.

This study is a Phase I dose-escalation open-label study to determine the MTD of M2ES in Subjects With Advanced Solid Tumors the recommended Phase II dose.The recommended dose and regimen of M2ES will be selected to perform the pharmacokinetic study profiles.

• Drug: M2ES 7.5mg
  M2ES 7.5mg
  Other Name: M2ES 7.5mg IV D1,8,15,22, every 28days a cycle.
• Drug: M2ES 15mg
  M2ES 15mg
  Other Name: M2ES 15mg IV D1,8,15,22, every 28days a cycle.
• Drug: M2ES 30mg
  M2ES 30mg
  Other Name: M2ES 30mg IV D1,8,15,22, every 28days a cycle.
• Drug: M2ES 60mg
  M2ES 60mg
  Other Name: M2ES 60mg IV D1,8,15,22, every 28days a cycle.

• Experimental: M2ES 7.5mg
  M2ES 7.5mg
  Intervention: Drug: M2ES 7.5mg
• Experimental: M2ES 15mg
  M2ES 15mg
  Intervention: Drug: M2ES 15mg
• Experimental: M2ES 30mg
  M2ES 30mg
  Intervention: Drug: M2ES 30mg
• Experimental: M2ES 60mg
  M2ES 60mg
  Intervention: Drug: M2ES 60mg

Inclusion Criteria:

1. 18 to 60 years of age
2. patients had histologically or cytologically confirmed solid tumors that was refractory to standard therapy.
3. life expectancy of at least 3 months.
4. ECOGPS ≤ 1
5. Adequate hematologic, renal, and hepatic function was required as determined by the following: WBC ≥4×109/L, absolute neutrophil count ≥ 1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥ 9g/dL, total bilirubin ≤1.5 upper limit of normal [ULN],AST ≤ 2.5 ULN, or ≤ 5 ULN if there was evidence of liver metastases; alkaline phosphatase ≤ 2.5 ULN, or ≤ 5 ULN if there was evidence of liver Metastases; creatinine clearance ≥50 mL/min.

Exclusion Criteria:

1. Pregnant and latent women, no contraception for women of childbearing age
2. Have taken other treatments
3. Be allergic to endostatin and other ingredient
4. Gastrointestinal Hemorrhage
5. Have Participated any clinical trail during the last 4 week
6. ECG: QTC ≥ 480 ms
7. patients had clinically apparent CNS disease ( primary brain tumors, tumor related apoplexy, CNS metastases, carcinomatous meningitis.)
8. Cardiovascular and mental disease
9. HIV-1 infected
10. HBV, HBV infected ,Hepatitis B surface antigen positive
11. Patients on therapeutic doses of heparin or antiplatelet agents.