A Clinical Investigation on the Efficacy of Leuprorelin Acetate (Androgen Deprivation Therapy) Combined With Sintilimab (Anti-PD-1) in Advanced Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of Participants with Stable Disease (SD)
研究概览
简要总结
Androgen Deprivation Therapy (ADT) triggers thymic revitalization and increases thymic output, enhancing baseline anti-tumor immunity and responses to immunotherapies. Anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. This study is to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.
详细描述
Immune checkpoint blockades (ICBs) are widely used in the clinical treatment of lung cancer. Studies have shown that the quantity and function of tumor-infiltrating lymphocytes (TILs) are associated with the effectiveness of PD-1 inhibitors in treating advanced NSCLC. The thymus is crucial for the differentiation, development, and maturation of T cells. With age, thymic atrophy leads to immunosenescence, significantly affecting baseline anti-tumor immunity and responses to immunotherapies. Preliminary findings have indicated that androgen deprivation therapy (ADT) not only directly induces apoptosis in prostate cancer cells but also may exert anti-tumor effects by promoting thymic regeneration. Furthermore, anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. Therefore, this study aims to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients aged ≥60 years.
- •ECOG performance status score of 0 ~
- •Expected survival time of more than 3 months.
- •Histologically or cytologically diagnosed advanced lung cancer according to the TNM staging system established by AJCC.
- •Patients who have not previously received any anti-PD-1 treatment.
- •Patients with adequate bone marrow function, no significant hepatic, renal, or coagulation dysfunction as per laboratory test criteria.
- •At least one tumor lesion meeting the following criteria:
- •No prior local treatments such as radiotherapy
- •Not biopsied during the screening period (if biopsy needed, baseline tumor assessment at least 14 days after the screening biopsy).
- •Measurable at baseline (longest diameter of the lesion ≥10 mm; For a lymph node, short diameter ≥15 mm).
- •If only one measurable lesion, no prior local treatments such as radiotherapy.
- •Ability to understand and voluntarily sign a written informed consent form.
- •Willingness to follow the study protocol and follow-up examinations.
排除标准
- •Exclusion of cases that do not meet the inclusion criteria
研究组 & 干预措施
Conventional Treatment Group
40 cases in this group to receive the standard conventional treatment (Chemotherapy + PD-1 Monoclonal Antibody)
干预措施: Sintilimab (Drug)
Conventional Treatment Combined with Leuprolide Group
40 cases in this group to receive the standard conventional therapy (Chemotherapy + PD-1 Monoclonal Antibody) combined with Leuprorelin acetate, 3.75 mg
干预措施: Leuprorelin acetate + Sintilimab (Drug)
结局指标
主要结局
Number of Participants with Stable Disease (SD)
时间窗: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Lesion reduction not meeting PR criteria nor sufficient increase for PD, falling in between these two endpoints. The minimum sum of diameters during the study period can be used as a reference.
Composition of Peripheral Blood Lymphocytes
时间窗: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.
Assessment of peripheral blood lymphocyte composition, comparing patients before and after a treatment cycle
Number of Participants with Disease Progression (PD)
时间窗: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
A 20% increase in the sum of the diameters of all measurable target lesions over the entire study period (using the smallest baseline value if it is the smallest), coupled with an absolute increase in the sum of diameters of at least 5mm. The appearance of one or more new lesions is also considered disease progression.
Status of Recent Thymic Emigrants (RTEs)
时间窗: Evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.
Assessment of the status of Recent Thymic Emigrants (RTEs), comparing patients before and after a treatment cycle
Number of Participants with Complete Response (CR)
时间窗: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Disappearance of all target lesions, with nodular diseases excluded and target nodules reduced to \<10mm in short axis.
Quantity of Peripheral Blood Lymphocytes
时间窗: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment
Assessment of peripheral blood lymphocyte quantity, comparing patients before and after a treatment cycle
Number of Participants with Partial Response (PR)
时间窗: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
Reduction of at least 30% in the sum of diameters of all measurable target lesions compared to baseline
次要结局
未报告次要终点
研究者
Yu Zhang
Professor
Jinzhou Medical University