Small Cell Lung Carcinoma
Conditions
Brief summary
This study plans to enroll limited-stage small cell lung cancer (LS-SCLC) patients who have achieved disease control after concurrent chemoradiotherapy (cCRT). Tissue samples collected at initial diagnosis and serial peripheral blood samples obtained at multiple post-cCRT timepoints will be analyzed using targeted next-generation sequencing to investigate the correlation between molecular residual disease (MRD) status and tumor recurrence/metastasis. For patients with MRD-positive results, a therapeutic strategy combining immunotherapy with anti-angiogenic agents will be implemented with the aim of improving clinical outcomes.
Interventions
Patients with MRD Positive will receive adebrelimab (1200 mg, D1, Q3W) , followed by ctDNA monitoring every 2 months (Year 1) and every 3 months (Year 2).The above treatment regimen will be maintained until disease progression, intolerable toxicity, completion of two years of treatment, subject-initiated withdrawal, or investigator-determined discontinuation.
Apatinib Mesylate Tablets (250 mg, QD) , followed by ctDNA monitoring every 2 months (Year 1) and every 3 months (Year 2).The above treatment regimen will be maintained until disease progression, intolerable toxicity, completion of two years of treatment, subject-initiated withdrawal, or investigator-determined discontinuation.
Sponsors
Peking University Cancer Hospital & Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
MRD-positive subjects will receive treatment with adebrelimab (anti-PD-L1) combined with apatinib (anti-angiogenic therapy),with close monitoring for disease progression.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent; age \>18 and \<80 years; 2. Histologically or cytologically confirmed limited-stage small cell lung cancer (LS-SCLC); 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-1; 4. Patients who have achieved disease stabilization after concurrent or sequential chemoradiotherapy; 5. Patients who had not received previous immune checkpoint inhibitor treatment; 6. Patients with MRD-positive status following concurrent chemoradiotherapy; 7. Willingness to provide clinical-pathological data, imaging studies, and other required materials for research purposes; compliance with follow-up procedures, including blood sample collection at predefined efficacy evaluation timepoints; and agreement to use the collected data for subsequent research analyses.
Exclusion criteria
1. Have other malignant tumors; 2. Autoimmune disorders that are not amenable to PD-L1 inhibitor therapy; 3. Prior exposure to other anti-angiogenic small molecule TKIs such as erlotinib or anti-angiogenic monoclonal antibodies such as bevacizumab (except locally infused bevacizumab); or participation in a clinical trial of another antineoplastic agent within 4 weeks prior to the first dose of ; or prior treatment with a paclitaxel; 4. Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg despite optimal pharmacologic therapy); 5. Class II or greater myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc intervals ≥450 ms in men and ≥470 ms in women). According to NYHA criteria, grade III-IV cardiac insufficiency, or cardiac color ultrasound suggests that the left ventricular ejection fraction (LVEF) is \<50% have had a myocardial infarction within 6 months prior to enrollment, New York Heart Association class II or higher heart failure, uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or ECG suggestive of acute ischemia or active conduction system abnormalities; (6) uncontrolled angina pectoris, uncontrolled severe ventricular arrhythmias, clinically significant pericardial disease, or ECG suggestive of acute ischemia or active conduction system abnormalities. 6. Uncontrolled co-morbidities including, but not limited to, poorly controlled diabetes mellitus, diabetic peripheral lesions , persistent infections, or psychiatric or social conditions that may interfere with the subject's ability to comply; 7. Abnormal coagulation (INR \> 1.5 or Prothrombin Time (PT) \> ULN + 4 seconds or APTT \> 1.5 ULN), hemorrhagic symptoms, or on thrombolytic or anticoagulant therapy; 8. Known hereditary or acquired bleeding and thrombotic disorders such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.; 9. Significant coughing up of fresh blood or hemoptysis of one-half teaspoon (2.5 ml) per day or more within 2 months prior to entry into the study ; 10. Failure to receive specified treatment or change in treatment regimen prior to disease progression; 11. Unable to cooperate with the study in accordance with the established clinical follow-up period; 12. Unable to accept or provide the specified means of efficacy assessment such as imaging. 13. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Negative conversion rate of MRD | MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first. | Patients with limited-stage small cell lung cancer (LS-SCLC) receive concurrent chemoradiotherapy in accordance with standard diagnostic and treatment guidelines. Patients who are MRD-positive after completion of concurrent chemoradiotherapy and have not previously been treated with immune checkpoint inhibitors are screened and enrolled to receive the investigational treatment regimen. We then calculate the proportion of patients whose MRD status converts from positive to negative following treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Imaging assessments are performed every 3 months. After each assessment, treatment response is evaluated by senior experts according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The maximum follow-up duration is 2 years. | Progression-Free Survival (PFS) is defined as the time interval from randomization (or treatment initiation in single-arm studies) to the first occurrence of either: Radiographically or pathologically confirmed disease progression（RECIST1.1）, or Death from any cause; whichever is observed first. |
| OS | Imaging assessments are performed every 3 months. After each assessment, treatment response is evaluated by senior experts according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The maximum follow-up duration is 2 years. | Overall Survival (OS) is defined as the time interval from randomization (or treatment initiation in single-arm studies) to death from any cause. |
| Time to conversion to MRD negativity | MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first. | Patients with limited-stage small cell lung cancer (LS-SCLC) receive concurrent chemoradiotherapy in accordance with standard diagnostic and treatment guidelines. Patients who are MRD-positive after concurrent chemoradiotherapy and have no prior exposure to immune checkpoint inhibitors are screened and enrolled to receive the investigational treatment regimen. The time required for MRD conversion from positive to negative following treatment is calculated, measured in days. |
| Duration of negative conversion after medication in MRD-positive patients | MRD is assessed at 60-day intervals during the first year and 90-day intervals during the second year, until disease progression, study discontinuation for any reason, or completion of 2 years of follow-up, whichever occurs first. | Patients with limited-stage small cell lung cancer (LS-SCLC) receive concurrent chemoradiotherapy in accordance with standard diagnostic and treatment guidelines. Patients who are MRD-positive after concurrent chemoradiotherapy and have no prior exposure to immune checkpoint inhibitors are screened and enrolled to receive the investigational treatment regimen. The duration of MRD negativity after treatment-defined as the time from conversion to MRD-negative status to subsequent reversion to MRD-positive status, if applicable-is calculated and measured in days. |
Countries
China
Contacts
CONTACTJun Zhao
PRINCIPAL_INVESTIGATORJun Zhao
Peking University Cancer Hospital & Institute
Outcome results
None listed