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

Обзор

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.

Вмешательства

• Лучевая терапия Stereotactic body radiotherapy (SBRT)
  Radiation source: 6MV photon linear gas pedal is used. Position immobilization: supine position, hands up, vacuum bag or styrofoam immobilization. Radiotherapy plan design: 4DCT positioning, radiotherapy plan design at 20% respiratory time-phase CT, isocentric irradiation, IMRT or VMAT design. Definition of target area: Gross tumor volume (GTV) includes the primary tumor in the lung, excluding lymph nodes. Internal target volume (ITV); Internal target volume (ITV) is formed by the fusion of 1
• Препарат Tislelizumab
  PD-L1 inhibitor
• Препарат Chemotherapy
  platinum-based double-agent chemotherapy

Первичные конечные точки

• event-free survival [Срок оценки: 5 years]

Вторичные конечные точки (5)

• major pathologic response (MPR) rate [Срок оценки: 1-year]
• pathological complete response (PCR) rates [Срок оценки: 1-year]
• R0-resection rate [Срок оценки: 1-year]
• overall survival [Срок оценки: 5 years]
• safety [Срок оценки: 1-year]

Критерии участия

Критерии включения

• 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 \> 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 \> 40% predicted; viii. International Normalized Ratio/activated partial thromboplastin time (INR/APTT) within the normal range; 6. Age 18-75

Критерии исключения

• 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 \> 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 \> 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT06598527 · B2024-495-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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