SCLC, Extensive Stage
Conditions
Brief summary
This single-arm phase II study aims to evaluate the efficacy and safety of lomustine combined with anlotinib in patients with extensive-stage small cell lung cancer resistant to second-line and above systemic treatment.
Detailed description
This is a single-arm phase II clinical study evaluating the efficacy and safety of lomustine combined with anlotinib in extensive-stage small cell lung cancer resistant to second-line and subsequent treatments. A total of 46 patients with extensive-stage small cell lung cancer who have received at least two lines of prior systemic therapy will be enrolled and treated with lomustine plus anlotinib. The primary endpoint is investigator-assessed objective response rate (ORR). Secondary endpoints include investigator-assessed progression-free survival (PFS), investigator-assessed disease control rate (DCR), intracranial response rate assessed per RANO criteria (RANO-IRR), investigator-assessed overall survival (OS), adverse events, quality of life (QOL) scores and safety profiles.
Interventions
DRUGLomustine
Oral lomustine 60 mg/m² once daily on day 1, every 6 weeks
DRUGAnlotinib
Oral administration, initial dose 12 mg, 10 mg or 8 mg once daily on days 1-14 of every 3-week cycle
Sponsors
Yayi He
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study with no masking applied to any parties involved in the trial.
Intervention model description
Single-center, single-arm, open-label, non-randomized, exploratory interventional study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1: Aged 18-75 years, without gender restriction. 2: Histologically or cytologically confirmed diagnosis of small cell lung cancer (SCLC), classified as extensive-stage disease according to the Veterans Administration Lung Study Group (VALSG) staging system. 3: Has received at least two lines of prior systemic antitumor therapy. 4: Has at least one measurable lesion as defined by RECIST 1.1 criteria. 5: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 6: Adequate organ function meeting the following criteria: Hematological function: Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count (PLT) ≥ 100×10⁹/L; hemoglobin (Hb) ≥ 90 g/L. Hepatic and renal function: Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5×ULN (≤ 5×ULN for patients with liver metastases); serum creatinine (Cr) ≤ 1.5×ULN; estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m². Coagulation function: International normalized ratio (INR) ≤ 1.5; activated partial thromboplastin time (APTT) ≤ 1.5×ULN. 7: Expected survival time ≥ 3 months. 8: Voluntarily signs the informed consent form and is willing and able to comply with the study protocol and follow-up requirements.
Exclusion criteria
* 1: Previous treatment with lomustine, anlotinib, or other similar anti-angiogenic TKIs. 2: Uncontrolled central nervous system (CNS) metastases (e.g., unstable or symptomatic brain metastases, or those requiring ongoing glucocorticoid therapy). 3: Active bleeding or high bleeding risk (e.g., history of massive gastrointestinal hemorrhage or cerebral hemorrhage within the past 6 months, or presence of unhealed wounds or ulcers). 4: Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) or severe cardiovascular diseases (e.g., myocardial infarction, severe arrhythmia, heart failure within the past 6 months). 5: Active infection (such as pneumonia, sepsis) or uncontrolled systemic diseases (such as uncontrolled diabetes, autoimmune diseases). 6: Pregnant or lactating females. Female participants must use effective contraception during treatment and for 6 months after the last dose of study treatment; male participants must use effective contraception during treatment and for 3 months after the last dose of study treatment. 7: History of other malignant tumors within the past 5 years, except for cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and other cured malignancies. 8: Known hypersensitivity to lomustine, anlotinib, or any excipient in their formulations. 9: Any other condition deemed inappropriate for participation in this study by the investigator (e.g., mental disorders, inability to comply with follow-up procedures).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Baseline at screening, after every 2 treatment cycles (each cycle is 21 days), end of treatment, up to disease progression, assessed up to approximately 24 months | Investigator-assessed ORR per RECIST 1.1 in ES-SCLC patients treated with Lomustine combined with anlotinib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | Date of first study treatment to date of disease progression or death from any cause, last follow-up, assessed up to approximately 24 months | Time from first treatment to disease progression or death from any cause, whichever occurs first |
| Disease Control Rate (DCR) | Time Frame: Baseline and after every 2 treatment cycles (each cycle is 21 days), up to disease progression, death, or study withdrawal, whichever occurs first，assessed up to approximately 24 months | According to RECIST 1.1, proportion of subjects achieving CR, PR, or stable disease (SD) in total enrolled population |
| Adverse Event (AE) | From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months | Record all new or worsening unfavorable medical events, grade and calculate incidence according to CTCAE 5.0 |
| Quality of Life Score（QOL Score） | At baseline, every 6 weeks during treatment until disease progression or death，assessed up to approximately 24 months | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was adopted for patient self-assessment. The scale consists of 30 items, including 5 functional scales, 9 symptom scales and 1 global health status / quality of life scale. Each item is scored on a 1-4 Likert scale, and all scale scores are standardized to a range of 0-100. Higher scores in functional and global quality of life scales and lower scores in symptom scales indicate better quality of life and health status of patients. |
Outcome results
None listed