Clinical trial NCT05496166: The Efficiency of Surgery and Radiotherapy After SHR-1316 (Adebrelimab) and Platinum-containing Doublet Induction Therapy for Limited-stage Small Cell Lung Cancer
Official title: Comparing the Efficiency Between Surgery and Radiotherapy After SHR-1316 (Adebrelimab) and Platinum-containing Doublet Induction Therapy for Limited-stage Small Cell Lung Cancer: a Randomized, Controlled, Open-label, Single-center Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Limited Stage Small Cell Lung Cancer
Keywords: LD-SCLC
surgery
radiotherapy
neoadjuvant chemoimmunotherapy
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
Collaborators: name: Jiangsu HengRui Medicine Co., Ltd.
First posted: 2022-08-11
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the efficiency between surgery and radiotherapy after SHR-1316 (Adebrelimab)and platinum-containing doublet induction therapy for limited-stage small cell lung cancer

Detailed description: 1.1 Main purpose To compare the efficiency between surgery and radiotherapy after therapy with SHR-1316 and chemotherapy for limited-stage small cell lung cancer according to progression-free survival (PFS) 1.2 Secondary Purpose The incidence of adverse events (AEs) during treatment was assessed to identify the safety of SHR-1316 and chemotherapy combined with surgery or radiotherapy according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

To evaluate the pathological response rate (MPR and PCR) of the surgical population after neoadjuvant therapy with SHR-1316 and chemotherapy for operable LD-SCLC according to the evaluation criteria of pathological response after neoadjuvant therapy recommended by the International Association for the Study of Lung Cancer (IASLC); To evaluate the overall survival (OS) of patients with limited-stage small cell lung cancer after therapy with SHR-1316 and chemotherapy combined with surgery or radiotherapy To evaluate the recurrence-free survival (RFS) in patients with limited-stage small cell lung cancer who received neoadjuvant SHR-1316 and chemotherapy combined with surgery; To evaluate the duration of response (DOR) in patients with limited-stage small cell lung cancer after SHR-1316 and chemotherapy combined with surgery or radiotherapy according to RECIST v1.1 To identify the impact on the health-related quality of life (HRQoL), mood, symptoms, sleep, etc. of patients undergoing surgery and radiotherapy after therapy with SHR-1316 and chemotherapy according to the Pulmonary Hospital Psychological Assessment Scale; 1.3 Exploratory Purpose To explore potential predictive biomarkers in archived and/or fresh tumor tissue and/or blood (or blood derivatives), including but not limited to programmed cell death protein ligand 1 (PD-L1) expression as determined by immunohistochemistry (IHC), gene expression profile (GEP), tumor mutational burden (TMB), tumor-infiltrating immune cell changes, etc., to evaluate the association of these markers with the study of treatment response or resistance mechanisms.

Eligibility criteria: Inclusion Criteria:

* after signing informed consent;
* Aged 18-70;
* Histologically or cytologically confirmed SCLC, imaging examination and other confirmed limited-stage small cell lung cancer, and without previous treatment;
* For clinical stage IIB-III, all patients should have clear lymph node pathology by EBUS to exclud occult lymph node metastasis.
* Two thoracic surgeons assessed thar it would be able to achieve radical surgery or R0 resection after 4 cycles of treatment. Surgical approaches include lobectomy, sleeve resection and pneumonectomy
* ECOG performance status score 0-1 points;
* With a life expectancy of at least 12 weeks;
* At least one measurable tumor
* With normal Other major organs (liver, kidney, blood system, etc.) function:

Absolute neutrophil count (ANC) ≥1.5×109/L, platelets ≥100×109/L, hemoglobin ≥90 g/L. Note: Patients should not receive blood transfusion or growth factor support within ≤ 14 days before blood collection during the screening period;

- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × upper limit of normal (ULN); Activated partial thromboplastin time (APTT) ≤ 1.5×ULN; Serum total bilirubin ≤ 1.5×ULN (total bilirubin in patients with Gilbert syndrome must be \<3×ULN); Aspartate and alanine aminotransferase (AST and ALT) ≤2.5×ULN, or AST and ALT ≤5×ULN in patients with liver metastases

* Female patients of childbearing potential must voluntarily use highly effective contraception during the study period until ≥ 120 days after the last dose of chemotherapy or SHR-1316, whichever is later, and have ≤ 7 days of urine or Serum pregnancy test results are negative;
* Unsterilized male patients must voluntarily use highly effective contraception during the study period until ≥120 days after the last dose of chemotherapy or SHR-1316, whichever is later.

Exclusion Criteria:

* Received any systemic anticancer therapy, including surgery, local radiotherapy, cytotoxic drug therapy, targeted drug therapy, and experimental therapy;
* Patients with other malignancies within five years prior to the start of the trial;
* Combined with unstable systemic diseases, such as uncontrolled hypertension, severe arrhythmia, etc;
* With active, known or suspected autoimmune disease, or autoimmune paraneoplastic syndrome requiring systemic therapy;
* Allergy to the test drug;
* Have or currently have interstitial lung disease;
* Coexisting with HIV infection or active hepatitis;
* Patients who have undergone other major surgery or severe trauma within 2 months before the start of the trial;
* Pregnant or breastfeeding women;
* Those who suffer from neurological diseases or mental illnesses who cannot cooperate;
* Other reasons that investigators deem inappropriate for enrollment.

Primary outcomes:
measure: progression-free survival
timeFrame: 2 years
Secondary outcomes:
measure: incidence of adverse events
timeFrame: through study completion, an average of 1.5 years
measure: pathological response
timeFrame: up to 5 months
measure: objective response rate
timeFrame: through study completion, an average of 1.5 years
measure: overall survival
timeFrame: up to 60 months
measure: recurrence free survival
timeFrame: up to 60 months
measure: the duration of response(DOR)
timeFrame: up to 60 months
Other outcomes:
measure: biological predicted markers
timeFrame: through study completion, an average of 1.5 years
Locations:
city: Shang'ai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
Study officials:
References: