A Study of Gimatecan (ST1481) in Small Cell Lung Cancer

A Phase Ib/II Study of Gimatecan (ST1481) for Small Cell Lung Cancer Patients Who Failed Standard Platinum-containing Chemotherapy

This phase Ib/II clinical trial studies the safety and effect of Gimatecan in small cell lung cancer patients who failed the first-line standard platinum-containing chemotherapy. The chemotherapy will be given every four weeks.

Key Inclusion Criteria:

1. Aged 18 to 75 years old of either gender;

2. A histopathological or cytological diagnosis of small cell lung cancer(SCLC);

3. Recurrence or progression disease after firstline platinum-containing chemotherapy and patients intolerant or unwilling to receive standard treatment;

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

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

6. Estimated life expectancy >4 months;

7. Taking drugs orally;

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

   1. white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L;
   2. ALT, AST and AKP ≤ 2.5×ULN; liver metastasis: ALT、AST≤ 5.0×ULN, ALP ≤ 6.0×ULN; bone metastases ALT、AST≤ 2.5×ULN, ALP ≤ 5.0×ULN;
   3. serum albumin ≥ 30g/L;
   4. total bilirubin ≤ 1.5×ULN;
   5. serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min;
   6. INR ≤ 1.5, PT≤ 1.5×ULN;

10. Serum HCG negative in premenopausal women, female patients of childbearing potential and male patients with female partners of childbearing potential must be willing to avoid pregnancy; 11. Ability to understand the study and sign informed consent.

Key exclusion Criteria:

1. Patients who have been treated previously for SCLC with two system chemotherapy (except for targeted therapy, immunotherapy and antiangiogenic therapy);
2. Patients who have been treated previously with topotecan, Irinotecan or other topoisomerase I inhibitors;
3. Known or suspected allergy or hypersensitivity to the investigational drug gimatecan ingredients or their analogues;
4. Other anticancer therapy including any investigational agent within 28 days prior to the first dose of the investigational drug gimatecan;
5. Patients who have been treated previously with intravenous or oral drugs that affect CYP isoenzymes within 7 days prior to the first dose of the investigational drug gimatecan;
6. Brain metastasis or meningeal metastasis (except for asymptomatic patients with lesion stable more than 28 days);
7. Major surgical intervention or trauma within 28 days prior to the first dose of investigational drug administration;
8. A history of gastrointestinal disease which affects drug absorption;
9. A history of allogeneic stem cell transplantation and organ transplantation;
10. A history of interstitial lung disease or non-infectious pneumonia;
11. Patients who cannot tolerate chemotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia;
12. A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases;
13. Presence of active hepatitis B (HBV DNA ≥ 200 IU/mL or 103 copies/mL), hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay);
14. A history of active pulmonary tuberculosis infection within 1 year or a history of active pulmonary tuberculosis infection more than 1 year ago but without formal anti-tuberculosis treatment;
15. A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer;
16. Pregnant or lactating women.