Nab-Paclitaxel Combined With Local Therapy in Relapsed SCLC

Phase 2Not Yet RecruitingNCT07547332

Shanghai Pulmonary Hospital, Shanghai, China84 enrolled

Overview

This is a prospective, single-arm, investigator-initiated clinical study (IIT) designed to evaluate the efficacy and safety of nab-paclitaxel combined with local radiotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed after first-line treatment. Small cell lung cancer (SCLC) is an aggressive type of lung cancer, and extensive-stage SCLC (ES-SCLC) refers to its advanced stage. For patients whose cancer progresses after first-line treatment, there are very limited effective second-line and later-line treatment options. Commonly used clinical regimens such as topotecan and lurbinectedin only provide modest improvements in tumor response and survival, and often cause severe hematological toxicities (represented by bone marrow suppression). This leaves patients in a persistent dilemma of "insufficient efficacy and limited tolerability", highlighting a clear unmet medical need for better treatment options in this population. Against this background, this study explores a comprehensive treatment strategy using nab-paclitaxel as the chemotherapy backbone, combined with local radiotherapy in eligible patients. Nab-paclitaxel is a nanoparticle albumin-bound form of paclitaxel, with a relatively controllable toxicity profile and manageable administration in clinical practice. Local radiotherapy may create a synergistic effect by improving the tumor immune microenvironment and enhancing local tumor control, with the goal of providing better evidence for a "chemotherapy ± local therapy" combination as a second-line treatment option.

Patients with extensive-stage small cell lung cancer (ES-SCLC) who progress after first-line therapy have very limited second-line and subsequent treatment options. Commonly used regimens such as topotecan and lurbinectedin yield modest tumor response and survival benefits, and are often associated with prominent hematologic toxicities, especially myelosuppression. This creates a clinical dilemma of "insufficient efficacy combined with limited tolerability" and reflects a clear unmet medical need in this population. This study explores a combined therapeutic strategy using nab-paclitaxel as the chemotherapy backbone with the addition of local radiotherapy in eligible patients. The primary objective is to evaluate whether this combination can provide clinically meaningful disease control and favorable signals for progression-free survival (PFS) and overall survival (OS), while maintaining an acceptable safety profile and manageable toxicities. Preclinical and clinical evidence suggests that nab-paclitaxel has a relatively controllable toxicity profile and convenient administration. Local therapy may exert synergistic effects by improving the tumor immune microenvironment and enhancing local tumor control, potentially supporting a more effective "chemotherapy ± local therapy" approach in the second-line setting. Given the lack of a standardized control regimen and high patient heterogeneity in this field, a single-arm design is employed to rapidly obtain efficacy signals and define the safety boundary, which will support future larger-sample controlled studies and clinical pathway optimization. This is a prospective, multicenter, single-arm, investigator-initiated trial (IIT) evaluating the efficacy and safety of nab-paclitaxel combined with local therapy in patients with ES-SCLC who have progressed after first-line or subsequent treatment. The study is planned to enroll 84 patients over 5 years, from January 2026 to December 2030, across two participating sites: Zhejiang Cancer Hospital (Principal Investigator: Weimin Mao) and Guangdong Provincial People's Hospital (Principal Investigator: Jiatao Zhang). The sample size was calculated based on historical data showing a median PFS of 3 months for second-line treatment in ES-SCLC. Assuming the study regimen improves median PFS to 4.5 months, with a two-sided α of 0.05 and 80% power, 75 patients are required. Accounting for a 10% dropout rate, a total of 84 patients will be enrolled. Eligibility Criteria Inclusion Criteria Signed written informed consent. Age 18-75 years, male or female. ECOG performance status 0 or 1. Histologically or cytologically confirmed ES-SCLC per the VALG staging system. Disease progression after at least one line of prior systemic therapy. Asymptomatic, treated central nervous system (CNS) metastases allowed if all of the following are met: Only supratentorial or cerebellar metastases; no brainstem, pons, medulla, or spinal cord metastases. No ongoing corticosteroid therapy for CNS disease. No stereotactic radiotherapy within 7 days before randomization. No progression after CNS-directed therapy. New asymptomatic CNS lesions must receive radiotherapy or surgery before enrollment. At least one measurable lesion per RECIST v1.1. Previously irradiated lesions are considered measurable only if they have progressed and are not the only lesions. Adequate hematologic, hepatic, renal, and coagulation function within 14 days before randomization. Availability of archival or newly obtained tumor tissue for biomarker analysis. Exclusion Criteria Active or untreated CNS metastases. Spinal cord compression not definitively treated or unstable. Leptomeningeal disease. Uncontrolled pleural, pericardial effusion, or ascites requiring frequent drainage. Uncontrolled hypercalcemia (\>1.5 mmol/L ionized calcium). History of other malignancy within 5 years except curatively treated in situ carcinoma, non-melanoma skin cancer, or localized disease with negligible risk of recurrence. Pregnant or breastfeeding women. Severe hypersensitivity to study drugs or excipients. History of autoimmune disease requiring systemic immunosuppression. Interstitial lung disease, active pneumonitis, or severe pulmonary fibrosis. HIV infection, active hepatitis B or hepatitis C. Active tuberculosis. Severe uncontrolled infection requiring hospitalization. Significant cardiovascular disease including NYHA Class II-IV heart failure, myocardial infarction within 3 months, unstable arrhythmia or angina. Major surgery within 28 days before randomization. Prior allogeneic bone marrow or solid organ transplantation. Prior CD137 agonist, anti-PD-1, or anti-PD-L1 therapy. Systemic immunosuppressive therapy within 14 days before randomization (except low-dose corticosteroids for specific indications). Hypersensitivity to platinum or etoposide. Discontinuation Criteria Patients will discontinue study treatment in cases of: Confirmed disease progression per RECIST v1.1; Withdrawal of consent; Sponsor-initiated study termination; Death; Unacceptable toxicity; Clinical deterioration; Initiation of new anticancer therapy; Progressive disease in critical anatomical sites such as leptomeninges. Study Termination Criteria Individual patients may be withdrawn for: Voluntary withdrawal; Poor compliance; Treatment-related serious adverse events (SAEs); Dose-limiting toxicities (DLT) or grade ≥3 treatment-related adverse events (TRAEs) unresponsive to dose modification; Severe comorbidities; Safety concerns by the investigator or IRB. Treatment Plan Study Drug Nab-paclitaxel for injection, 100 mg, provided free of charge by Qilu Pharmaceutical (Hainan) Co., Ltd. Store at 20-30°C, protected from light, shelf life 36 months. Regimen Nab-paclitaxel administered intravenously every 3 weeks for up to 6 cycles. Local radiotherapy may be delivered concurrently or sequentially, determined by the radiation oncologist based on performance status, disease burden, lesion location, chemotherapy tolerance, bone marrow reserve, and risk of acute toxicity. Radiotherapy targets at least one progressive lesion, prioritizing primary lung lesions, symptomatic metastases, or lesions at risk of serious complications. Dose and fractionation are individualized based on location, tumor size, treatment sequence, and normal tissue constraints. Efficacy Assessment Primary Endpoint Progression-free survival (PFS), defined as time from first dose to first documented progression per RECIST v1.1 or death from any cause, whichever occurs first. Secondary Endpoints Overall survival (OS), time from first dose to death from any cause. Objective response rate (ORR), proportion of patients with complete response (CR) or partial response (PR). Disease control rate (DCR). Duration of response (DOR). 6-month and 12-month PFS rates. 12-month and 24-month OS rates. Timing of Evaluations Baseline imaging within 28 days before first treatment. Tumor assessment every 9 weeks (±7 days) until progression, new anticancer therapy, or withdrawal. Survival follow-up every 12 weeks (±14 days) after progression or treatment discontinuation. Safety Assessment Safety is evaluated throughout treatment and follow-up using NCI-CTCAE v5.0. Baseline assessment within 28 days before treatment. Cycle safety evaluations include adverse events (AEs), laboratory tests, physical examination, and vital signs. A follow-up safety visit is performed 30 days (±7 days) after last dose. Non-resolving AEs are followed until resolution, stabilization, or study end. Adverse Events Treatment-emergent adverse events (TEAEs) are defined as any AE occurring from first dose through the post-treatment observation period. All AEs are coded using MedDRA 24.0 or higher and graded by severity. Summary tables will be generated by system organ class (SOC), preferred term (PT), severity, relatedness, and outcome. Ethics The study will be conducted in accordance with the Declaration of Helsinki, ICH-GCP, and relevant national regulations. The protocol has been approved by the Institutional Review Board/Ethics Committee. Patient confidentiality will be strictly maintained. Data Management All data will be recorded in case report forms consistent with source documents. Research records will be stored per local regulatory requirements. Patient identifiers will be protected and anonymized before submission to the sponsor. Statistical Analysis Descriptive statistics will be used for baseline and demographic data. Time-to-event endpoints (PFS, OS, DOR) will be analyzed using the Kaplan-Meier method. Median values and 95% confidence intervals (CI) will be estimated. ORR and DCR will be presented as proportions with 95% CIs calculated by the Clopper-Pearson method. Safety will be summarized descriptively by frequency, severity, relatedness, and outcome. No imputation will be performed for missing data. Statistical analyses will be performed using SAS, R, or SPSS.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * (1) Written informed consent has been signed. (2) Male or female, aged 18-75 years. (3) Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. (4) Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC) according to the Veterans Administration Lung Group (VALG) staging system. (5) Patients with ES-SCLC who have received at least one prior line of systemic therapy. (6) Patients with previously treated asymptomatic central nervous system (CNS) metastases are eligible if all of the following criteria are met: * Only supratentorial and cerebellar metastases (i.e., no metastases in the midbrain, pons, medulla oblongata, or spinal cord); * No requirement for ongoing corticosteroid therapy for CNS disease; * No stereotactic radiotherapy within 7 days prior to randomization; * No disease progression observed on imaging from completion of CNS-directed therapy through screening; ⑤ If new asymptomatic CNS metastases are detected on screening imaging, patients must receive radiotherapy and/or resection of CNS lesions. After such treatment, these patients may be randomized without additional brain scans if all other eligibility criteria are satisfied. (7) Presence of measurable disease as defined by RECIST v1.1. A previously irradiated lesion may be considered measurable only if clear disease progression has occurred after radiotherapy and the lesion is not the only site of disease. (8) Adequate hematologic and end-organ function as defined by laboratory results obtained within 14 days prior to randomization: * Absolute neutrophil count (ANC) ≥ 1500 cells/μL without granulocyte colony-stimulating factor support; lymphocyte count ≥ 500 cells/μL; * Platelet count ≥ 100,000/μL without transfusion; hemoglobin ≥ 9.0 g/dL (may be achieved by transfusion); ③ International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤ 1.5 × upper limit of normal (ULN). This criterion applies only to patients not receiving anticoagulation. Patients on anticoagulation must be on a stable dose; ④ Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 × ULN, except: Patients with confirmed liver metastases: AST and/or ALT ≤ 5 × ULN; Patients with confirmed liver or bone metastases: alkaline phosphatase ≤ 5 × ULN; * Serum bilirubin ≤ 1.25 × ULN. For patients with known Gilbert's disease, serum bilirubin ≤ 3 × ULN is permitted; * Serum creatinine ≤ 1.5 × ULN. (9) Patients must provide a pre-treatment tumor tissue sample during the study. Any available tumor tissue sample is acceptable. Submission may be completed after enrollment. Exclusion Criteria: * Patients meeting any of the following criteria are ineligible: Active or untreated CNS metastases detected by computed tomography (CT) or magnetic resonance imaging (MRI) during screening or on prior imaging. Spinal cord compression not radically treated with surgery and/or radiotherapy, or previously diagnosed spinal cord compression without clinical evidence of stable disease for at least 1 week prior to randomization. Leptomeningeal metastases. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once per month or more frequently); indwelling catheters are not permitted. Uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium, serum calcium \> 12 mg/dL, or corrected serum calcium \> ULN). History of malignancy other than SCLC within 5 years prior to randomization, except for malignancies with negligible risk of metastasis or death (e.g., 5-year OS \> 90%) and curative potential after treatment, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer with radical surgery, or ductal carcinoma in situ with radical surgery. Pregnant or lactating women, or women planning pregnancy during the study period. History of severe allergic, hypersensitivity, or anaphylactic reactions to chimeric, humanized, or human antibodies or fusion proteins. Known hypersensitivity to any component of biologic medicinal products produced in Chinese hamster ovary (CHO) cells or to the study drug formulation. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, and glomerulonephritis. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid hormone replacement therapy are eligible. Patients with type 1 diabetes mellitus controlled on a stable insulin regimen are eligible. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo only (patients with psoriatic arthritis are excluded) may be enrolled if: * Rash involves \< 10% of body surface area; ② Disease is well controlled at baseline requiring only low-potency topical corticosteroids; ③ No acute exacerbation of underlying disease in the past 12 months (no requirement for PUVA, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high-potency or oral corticosteroids). History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonia, or active pneumonitis on screening chest CT scan. Severe interstitial lung disease. Positive human immunodeficiency virus (HIV) test. Active hepatitis B (chronic or acute; defined as positive hepatitis B surface antigen \[HBsAg\] at screening) or hepatitis C virus (HCV) infection. Patients with resolved or prior HBV infection (positive hepatitis B core antibody \[HBcAb\] and negative HBsAg) are eligible. HBV DNA testing must be performed prior to randomization. Among patients positive for HCV antibody, only those with negative HCV RNA by PCR are eligible. Active tuberculosis. Severe infection at enrollment, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc. Severe cardiovascular disease, such as New York Heart Association (NYHA) Class II or higher heart failure, myocardial infarction within 3 months prior to randomization, unstable arrhythmia, or unstable angina. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction \< 50% must be on optimal stable therapy as judged by the treating physician, with cardiology consultation if necessary. Major surgery within 28 days prior to randomization (except diagnostic surgery) or expected major surgery during the study. History of allogeneic bone marrow transplantation or solid organ transplantation. Any other disease, metabolic dysfunction, physical finding, or laboratory abnormality that, in the investigator's judgment, would contraindicate use of the study drug, interfere with interpretation of study results, or place the patient at high risk of treatment-related complications. Prior receipt of anti-tumor therapy for ES-SCLC. Treatment with any other investigational agent or participation in another therapeutic clinical trial within 28 days prior to randomization. Live attenuated vaccine within 4 weeks prior to randomization or anticipated need for such vaccines during the study. Prior treatment with CD137 agonists, immune checkpoint blockade therapy, anti-PD-1, or anti-PD-L1 therapeutic antibodies. Systemic immunosuppressive therapy within 2 weeks prior to randomization, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents. Patients receiving short-term, low-dose systemic immunosuppression (e.g., single-dose dexamethasone for nausea) may be eligible after discussion and approval by the investigator and medical monitor. Use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for orthostatic hypotension, and low-dose corticosteroid replacement for adrenal insufficiency is permitted. History of hypersensitivity to platinum agents or etoposide.

Nab-Paclitaxel Combined With Local Therapy in Relapsed SCLC

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts