Lomustine Combined With Anlotinib as Interventional Therapy for Extensive-stage Small Cell Lung Cancer Resistant to Second-line and Above Treatment

Official title

A Single-arm, Phase II Interventional Study 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 Further Lines of Treatment

Overview

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

• Drug Lomustine
  Oral lomustine 60 mg/m² once daily on day 1, every 6 weeks
• Drug Anlotinib
  Oral administration, initial dose 12 mg, 10 mg or 8 mg once daily on days 1-14 of every 3-week cycle

Primary outcome measures

• Objective Response Rate [Time frame: 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]

Secondary outcome measures (4)

• progression free survival [Time frame: Date of first study treatment to date of disease progression or death from any cause, last follow-up, assessed up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: 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]
• Adverse Event (AE) [Time frame: From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months]
• Quality of Life Score（QOL Score） [Time frame: At baseline, every 6 weeks during treatment until disease progression or death，assessed up to approximately 24 months]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07632209 · 2026LY0102 · MR-31-26-032631

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗