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

Study Overview
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Brief Summary
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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.

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

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Gimatecan


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged 18 to 75 years old of either gender; A histopathological or cytological diagnosis of small cell lung cancer(SCLC); Recurrence or progression disease after firstline platinum-containing chemotherapy and patients intolerant or unwilling to receive standard treatment; Measurable cancer lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Eastern Cooperative Oncology Group(ECOG) performance status score 0-1; Estimated life expectancy >4 months; Taking drugs orally; The function of important organs meets the following requirements: white blood cell count (WBC) ≥ 4.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L; 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; serum albumin ≥ 30g/L; total bilirubin ≤ 1.5×ULN; serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min; 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: Patients who have been treated previously for SCLC with two system chemotherapy (except for targeted therapy, immunotherapy and antiangiogenic therapy); Patients who have been treated previously with topotecan, Irinotecan or other topoisomerase I inhibitors; Known or suspected allergy or hypersensitivity to the investigational drug gimatecan ingredients or their analogues; Other anticancer therapy including any investigational agent within 28 days prior to the first dose of the investigational drug gimatecan; 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; Brain metastasis or meningeal metastasis (except for asymptomatic patients with lesion stable more than 28 days); Major surgical intervention or trauma within 28 days prior to the first dose of investigational drug administration; A history of gastrointestinal disease which affects drug absorption; A history of allogeneic stem cell transplantation and organ transplantation; A history of interstitial lung disease or non-infectious pneumonia; Patients who cannot tolerate chemotherapy due to severe cardiac, lung, liver or kidney dysfunction, or hematopoietic disease or cachexia; A history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases; 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); 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; A history of malignancies other than esophageal cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or cured early prostate cancer; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gimatecan group<br>In Phase Ib study, patients will receive gimatecan at different dose level (0.4mg/m2, 0.6mg/m2,0.8mg/m2, oral, every 4 weeks) until progressive disease (PD).In Phase II study, patients will receive gimatecan at recommended phase II dose level. | Drug: Gimatecan<br>* Patients will receive gimatecan orally at the recommended dose level on day 1-5 every 4 weeks.<br>* Other names: ST1481;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicity (DLT) | Phase Ib: Number of patients experienced any dose limited toxicity over the DLT period. | up to 28 days. | 
| Recommended phase II dose (RP2D) | Phase Ib: Determination of recommended phase II dose of escalating dose of gimatecan for the phase II part of the study. | up to 12 months. | 
| Objective response rate (ORR) | Percentage of patients with objective response assessed by best overall response (BOR) of either complete response(CR) or partial remission(PR) will be reported. | To evaluate objective response rate every 8 weeks after the initiation of chemotherapy, up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The 2-year progression free survival of the whole group. | 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. | 
| Disease control rate (DCR) | Percentage of patients with disease control as assessed by best overall response (BOR) of either complete response(CR), partial remission(PR) or stable disease (SD) will be reported. | To evaluate disease control rate every 8 weeks after the initiation of chemotherapy, up to 24 months. | 
| Duration of Response (DoR) | The DoR applies only to patients whose BOR is either CR or PR. The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD). | First documented CR or PR, whichever is first recorded until the first assessment of PD, assessed up to 24 months. | 
| Overall survival (OS) | The 2-year overall survival of the whole group. | 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. | 
| Survival rate (SR) | Survival probability of patients calculated according to Kaplan-Meier curve at either 1 or 2 year. | up to 24 months. | 
| Treatment related adverse events rate | The incidence rate of treatment related adverse events of the whole group assessed by CTCAE v5.0. | From the enrollment to 30 days later of the last chemotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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small cell lung cancer, chemotherapy, gimatecan