A Phase II Study of Gimatecan (ST1481) in Locally Advanced or Metastatic Pancreatic Cancer

Key inclusion Criteria:

1. Histologically or cytologically confirmed pancreatic cancer originating frompancreatic ductal epithelium, excluding pancreatic endocrine tumor;

2. Locally advanced or metastatic pancreatic cancer in no condition for radicalradiotherapy or operation;

3. Failed in first-line gemcitabine or fluorouracil drugs chemotherapy (Recurrence within 6 months after treatment, progression or toxicity intolerance during treatment);

4. Chemotherapy, targeted therapy or radical radiotherapy should be stopped 3 weeks ago,immunotherapy should be stopped 4 weeks ago, and previous toxicity recovered (CTCAE ≤level 1);

5. Measurable cancer lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;

6. No younger than 18 years old of either gender;

7. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1;

8. Estimated life expectancy >3 months;

9. The function of important organs meets the following requirements:

10. absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 85×109/L, hemoglobin ≥ 90g/L;

11. serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min, U-pro < 2+ or 1.0g/L; if U-pro ≥2+ or 1.0g/L, 24 hours U-pro ≤ 1.0g/L can be included;

12. total bilirubin ≤ 1.5×ULN, obstructive jaundice with biliary drainage: totalbilirubin ≤ 2.0×ULN; alanine transaminase and aspartate aminotransferase ≤ 2.5×ULN, liver metastasis ≤ 5.0×ULN; serum albumin ≥ 30g/L;

13. Without a history of allergy or hypersensitivity to camptothecin drugs;

14. Taking drugs orally;

15. Serum human chorionic gonadotropin negative in premenopausal women; female patients ofchildbearing potential and male patients with female partners of childbearingpotential must be willing to avoid pregnancy;

16. Ability to understand the study and sign informed consent.

Key exclusion Criteria:

1. Patients who have been previously treated with camptothecin drugs or topoisomerase Iinhibitor within 6 months before enrollment;

2. Patients who have been previously treated with gemcitabine and fluorouracil infirst-line treatment within 6 months before enrollment;

3. Patients who have been previously treated with other investigational drugs within 4weeks before enrollment;

4. Patients with brain or meningeal metastasis;

5. Patients with a history of gastrointestinal disease which affects drug absorption;

6. Patients with serous cavity effusion with clinical symptoms (such as pleural effusion,peritoneal effusion, pericardial effusion, etc.), which continue to increase aftertwo-week conservative treatment (excluding puncture drainage);

7. Patients with hypertension that cannot be controlled by drugs (≥ 160/100mmhg); anginapectoris within 3 months before enrollment or unstable angina pectoris; myocardialinfarction within 1 year before enrollment and cardiac insufficiency (NYHA ≥ II);

8. Patients with active infections requiring systemic treatment or pyrexia of unknownorigin prior to initial administration (except neoplastic fever);

9. Patients with hepatitis B surface antigen positive and peripheral blood hepatitis Bvirus DNA ≥1.0×103 copy/mL; positive of hepatitis C antibody and peripheral bloodhepatitis C virus RNA;

10. Patients with active pulmonary tuberculosis or uncontrolled pulmonary tuberculosisafter anti-tuberculosis treatment;

11. Patients with a history of immunodeficiency (including a positive HIV test result), orother acquired or congenital immunodeficiency diseases;

12. Patients with a history of malignancies other than pancreatic cancer beforeenrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or malignanttumors that have been cured for 5 years;

13. Pregnant or lactating women;

14. Patients with a history of mental diseases (including epilepsy or dementia).