Clinical trial NCT04501029: A Study of Gimatecan (ST1481) in Small Cell Lung Cancer
Official title: A Phase Ib/II Study of Gimatecan (ST1481) for Small Cell Lung Cancer Patients Who Failed Standard Platinum-containing Chemotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Small Cell Lung Cancer
Keywords: small cell lung cancer
chemotherapy
gimatecan
Lead sponsor: Lee's Pharmaceutical Limited
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose limited toxicity (DLT)
timeFrame: up to 28 days.
measure: Recommended phase II dose (RP2D)
timeFrame: up to 12 months.
measure: Objective response rate (ORR)
timeFrame: To evaluate objective response rate every 8 weeks after the initiation of chemotherapy, up to 24 months.
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months.
measure: Disease control rate (DCR)
timeFrame: To evaluate disease control rate every 8 weeks after the initiation of chemotherapy, up to 24 months.
measure: Duration of Response (DoR)
timeFrame: First documented CR or PR, whichever is first recorded until the first assessment of PD, assessed up to 24 months.
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months.
measure: Survival rate (SR)
timeFrame: up to 24 months.
measure: Treatment related adverse events rate
timeFrame: From the enrollment to 30 days later of the last chemotherapy.
Other outcomes:
Locations:
city: Beijing
country: China
facility: The Fifth Medical Center of General Hospital of the Chinese People's Liberation Army
state: Beijing
Study officials:
affiliation: The Fifth Medical Center of the Chinese PLA General Hospital
name: LIU XIAOQING, MD
role: STUDY_DIRECTOR
References:
citation: Hurwitz JL, McCoy F, Scullin P, Fennell DA. New advances in the second-line treatment of small cell lung cancer. Oncologist. 2009 Oct;14(10):986-94. doi: 10.1634/theoncologist.2009-0026. Epub 2009 Oct 9.
citation: Owonikoko TK, Behera M, Chen Z, Bhimani C, Curran WJ, Khuri FR, Ramalingam SS. A systematic analysis of efficacy of second-line chemotherapy in sensitive and refractory small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):866-72. doi: 10.1097/JTO.0b013e31824c7f4b.