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
Overview
- Phase
- Phase 3
- Intervention
- Stereotactic body radiotherapy (SBRT)
- Conditions
- Lung Cancer (NSCLC)
- Sponsor
- Yang Hong
- Enrollment
- 360
- Locations
- 1
- Primary Endpoint
- event-free survival
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
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.
Investigators
Yang Hong
professor
Sun Yat-sen University
Eligibility Criteria
Inclusion Criteria
- •Patients voluntarily agree to participate and sign the informed consent;
- •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;
- •Pulmonary lesions will be assessed as resectable/potentially resectable by a multiple disciplinary team including thoracic surgeon;
- •Eastern Cooperative Oncology Group Performance Status 0 to 1
- •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;
Exclusion Criteria
- •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;
- •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;
- •Historical radiotherapy of chest
- •Active bleeding before treatment
- •Patents with sever heart, lung, liver, or kidney insufficiency
- •Diabetes more than 10-year; unsatisfactory blood glucose control
- •Patients with interstitial lung disease or non-infectious pneumonia
- •EGFR-mutations and ALK-fusion positive NSCLC
- •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;
- •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;
Arms & Interventions
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
Intervention: Stereotactic body radiotherapy (SBRT)
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
Intervention: Tislelizumab
neoadjuvant SBRT combined with immunochemotherapy
Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle
Intervention: Chemotherapy
neoadjuvant immunochemotherapy
Three cycles of Tislelizumab in conjunction with platinum-based chemotherapy were administered at three-week intervals. Surgical intervention was subsequently scheduled to occur within 4 to 6 weeks (±7 days) following the completion of the third chemotherapy cycle.
Intervention: Tislelizumab
neoadjuvant immunochemotherapy
Three cycles of Tislelizumab in conjunction with platinum-based chemotherapy were administered at three-week intervals. Surgical intervention was subsequently scheduled to occur within 4 to 6 weeks (±7 days) following the completion of the third chemotherapy cycle.
Intervention: Chemotherapy
Outcomes
Primary Outcomes
event-free survival
Time Frame: 5 years
include 2/3/5 event-free survival time
Secondary Outcomes
- major pathologic response (MPR) rate(1-year)
- pathological complete response (PCR) rates(1-year)
- R0-resection rate(1-year)
- overall survival(5 years)
- safety(1-year)