Clinical trial NCT06598527: Stereotactic Body Radiotherapy Followed by Tislelizumab Plus Platinum-based Chemotherapy Versus Tislelizumab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage Ⅱ-Ⅲ Non-small Cell Lung Cancer: A Phase Ⅲ, Randomized, Multicenter, Prospective Study
Official title: Stereotactic Body Radiotherapy Followed by Tislelizumab Plus Platinum-based Chemotherapy Versus Tislelizumab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage Ⅱ-Ⅲ Non-small Cell Lung Cancer: A Phase Ⅲ, Randomized, Multicenter, Prospective Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lung Cancer (NSCLC)
Keywords: NSCLC
SBRT
immunochemotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the efficacy and safety of neoadjuvant Stereotactic Body Radiotherapy (SBRT) combined with immunochemotherapy versus neoadjuvant immunochemotherapy. The main questions it aims to answer are:

Dose SBRT combined with immunochemotherapy improve event-free survival? Is SBRT combined with immunochemotherapy safe enough?

Participants will:

Receive neoadjuvant SBRT combined with immunochemotherapy or neoadjuvant immunochemotherapy.

Tumor assessment will be performed prior to surgery. Surgery will be performed within 4 to 6 weeks (+ 7 days) after completion of the last cycle of immunochemotherapy.


Eligibility criteria: Inclusion Criteria:

* 1. Patients voluntarily agree to participate and sign the informed consent; 2. Patients with cytologically/histologically diagnosed (by means of percutaneous lung aspiration biopsy, bronchoscopy, mediastinoscopy, etc.), untreated stage IIa-IIIa (according to the AJCC 8th edition of thoracic tumor staging) non-small cell lung cancer. In addition, patients with potentially resectable stage IIIb (T3-4N2) NSCLC will also be enrolled. All patients are required to receive PET/CT (or chest + upper abdominal CT + brain MRI) at baseline for clinical staging; 3. Pulmonary lesions will be assessed as resectable/potentially resectable by a multiple disciplinary team including thoracic surgeon; 4. Eastern Cooperative Oncology Group Performance Status 0 to 1 5. Requirements for hematology: i, neutrophils ≥ 1500 x 109/L; ii, platelets ≥ 100 x 109/L; iii, hemoglobin \&gt; 9.0 g/dL; iv, serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min; v, aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 x ULN; vi, total bilirubin ≤ 1.5 x ULN; vii. forced expiratory volume in the first second (FEV1) ≥ 1.2 L or \&gt; 40% predicted; viii. International Normalized Ratio/activated partial thromboplastin time (INR/APTT) within the normal range; 6. Age 18-75

Exclusion Criteria:

* 1. Patients with or suspected with autoimmune diseases. Note: patients with vitiligo, type 1 diabetes, hypothyroidism managed with hormone replacement therapy only (Hashimoto's thyroiditis) can be enrolled in the study when there is no clear evidence of recurrence; 2. Patients required systemic corticosteroids treatment (dose \&gt; 10 mg daily prednisolone \[or equivalent\]) or other immunosuppressive drugs within 14 days of enrollment. Note: inhaled or topical corticosteroids, or adrenal replacement therapy (dose \&gt; 10 mg daily prednisolone \[or equivalent\]) are acceptable for patients without apparent autoimmune disease; 3. Historical radiotherapy of chest 4. Active bleeding before treatment 5. Patents with sever heart, lung, liver, or kidney insufficiency 6. Diabetes more than 10-year; unsatisfactory blood glucose control 7. Patients with interstitial lung disease or non-infectious pneumonia 8. EGFR-mutations and ALK-fusion positive NSCLC 9. Patients with other prior malignancies (except skin malignancies other than non-melanoma, and carcinoma in situ at the following sites \[bladder, stomach, colorectal, endometrium, cervix, melanoma, or breast\]) are not eligible for enrollment in this study. However, if the prior malignancies remain in complete response (CR) for ≥ 2 years and no additional anti-cancer therapy is required during the study, such patients are permitted to be enrolled; 10. The patient is medically, psychologically, or physiologically unable to complete the study or to understand the Patient Information Sheet, in the opinion of the investigator; 11. Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA any other drugs specifically targeting T-cell co-stimulation or immunoregulation pathways; 12. Present active hepatitis B or hepatitis C 13. Patients with positive HIV test results or diagnosed with acquired immunodeficiency disease (AIDS); 14. Hypersensitivity to the investigational product; 15. Pregnant or lactating women.

Primary outcomes:
measure: event-free survival
timeFrame: 5 years
Secondary outcomes:
measure: major pathologic response (MPR) rate
timeFrame: 1-year
measure: pathological complete response (PCR) rates
timeFrame: 1-year
measure: R0-resection rate
timeFrame: 1-year
measure: overall survival
timeFrame: 5 years
measure: safety
timeFrame: 1-year
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: