NSCLC, Stage III, NSCLC, Stage IV
Conditions
Keywords
Androgen Deprivation Therapy （ADT）, Leuprorelin acetate, NSCLC, PD-1 inhibitor
Brief summary
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.
Detailed description
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.
Interventions
DRUGLeuprorelin acetate + Sintilimab
Leuprolide, an FDA-approved GnRH agonist, reduces sex hormone production and is widely used in clinical practice.
DRUGSintilimab
PD-1 inhibitor
Sponsors
The First Affiliated Hospital of Zhengzhou University
Jinzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
80 cases of stage III or IV NSCLC are randomly divided into two groups of 40 cases each. The control group is to receive conventional treatments (Chemotherapy + PD-1 Monoclonal Antibody), while the experimental group is to receive conventional treatments combined with Leuprorelin acetate.
Eligibility
Sex/Gender
MALE
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
3.Inclusion Criteria: 1. Male patients aged ≥60 years. 2. ECOG performance status score of 0 \ 1. 3. Expected survival time of more than 3 months. 4. Histologically or cytologically diagnosed advanced lung cancer according to the TNM staging system established by AJCC. 5. Patients who have not previously received any anti-PD-1 treatment. 6. Patients with adequate bone marrow function, no significant hepatic, renal, or coagulation dysfunction as per laboratory test criteria. 7. 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. 8. Ability to understand and voluntarily sign a written informed consent form. 9. Willingness to follow the study protocol and follow-up examinations.
Exclusion criteria
* Exclusion of cases that do not meet the inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Complete Response (CR) | 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. |
| Number of Participants with Partial Response (PR) | 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 |
| Number of Participants with Disease Progression (PD) | 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. |
| Number of Participants with Stable Disease (SD) | 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. |
| Quantity of Peripheral Blood Lymphocytes | 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 |
| Composition of Peripheral Blood Lymphocytes | 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 |
| Status of Recent Thymic Emigrants (RTEs) | 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 |
Countries
China
Contacts
Primary ContactWangzhi Wei
Backup ContactShuangning Yang
Outcome results
None listed