Clinical trial NCT06512207: A Study on the Efficacy of Androgen Deprivation Therapy Combined With Anti-PD-1 Therapy in Advanced Lung Cancer
Official title: A Clinical Investigation on the Efficacy of Leuprorelin Acetate (Androgen Deprivation Therapy) Combined With Sintilimab (Anti-PD-1) in Advanced Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: NSCLC, Stage III
NSCLC, Stage IV
Keywords: Androgen Deprivation Therapy （ADT）
Leuprorelin acetate
NSCLC
PD-1 inhibitor
Lead sponsor: Jinzhou Medical University
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Zhengzhou University
First posted: 2024-07-22
Enrollment: 80
Sex: MALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants with Complete Response (CR)
timeFrame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
measure: Number of Participants with Partial Response (PR)
timeFrame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
measure: Number of Participants with Disease Progression (PD)
timeFrame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
measure: Number of Participants with Stable Disease (SD)
timeFrame: Efficacy evaluations are scheduled at 6 weeks,12 weeks and 18 weeks post treatment
measure: Quantity of Peripheral Blood Lymphocytes
timeFrame: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment
measure: Composition of Peripheral Blood Lymphocytes
timeFrame: Laboratory evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.
measure: Status of Recent Thymic Emigrants (RTEs)
timeFrame: Evaluations are scheduled before treatment, at 3 weeks post-treatment, and at 6 weeks post-treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: The Third Oncology Ward, First Affiliated Hospital of Zhengzhou University
state: Henan
Study officials:
affiliation: Jinzhou Medical University
name: Yu Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
References: