NCT07309952

Neoadjuvant SBRT Followed by Sintilimab Plus Chemotherapy for N3-Positive NSCLC

Neoadjuvant Stereotactic Body Radiotherapy Followed by Sintilimab Plus Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer With Contralateral Mediastinal (N3) Lymph Node Metastasis: A Prospective Phase II Clinical Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Sponsor: Yang Hong · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase II clinical trial evaluating the efficacy and safety of a new treatment approach for patients with locally advanced non-small cell lung cancer (NSCLC) that has spread to lymph nodes on the opposite side of the chest (known as N3 lymph node involvement). The study will enroll 28 patients aged 18 to 75 years with previously untreated, potentially resectable NSCLC classified as stage IIIB-IIIC. Participants will receive a combination of stereotactic body radiation therapy (SBRT) to the primary lung tumor, followed by two cycles of sintilimab (an immunotherapy drug) plus platinum-based chemotherapy before surgery. The main goals of the study are to see whether this treatment can shrink or eliminate cancer in the contralateral mediastinal lymph node (lymph node downstaging) and allow more patients to undergo curative surgery. Secondary goals include assessing pathological response rates, surgical outcomes, survival, and safety. Patients will be closely monitored during and after treatment, with follow-up visits planned for up to 5 years after surgery.

Conditions

• Locally Advanced Non-Small Cell Lung Cancer
• Stage IIIb Non-small Cell Lung Cancer
• Stage IIIC Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Sintilimab	Sintilimab is an anti-PD-1 monoclonal antibody. In this study, it is administered intravenously at a fixed dose of 200 mg on Day 1 of each 3-week cycle. Patients receive 2 cycles of sintilimab in combination with platinum-based doublet chemotherapy. The first dose of sintilimab is initiated within 7 days after completion of stereotactic body radiotherapy (SBRT).
DRUG	Paclitaxel	Paclitaxel is a taxane chemotherapeutic agent. In this study, it is specifically used for patients with squamous cell non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 175 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of paclitaxel in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. Standard premedication to prevent hypersensitivity reactions is required prior to each infusion. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.
DRUG	Carboplatin (AUC 5)	Carboplatin is a platinum-based chemotherapeutic agent. In this study, it serves as the backbone chemotherapy for all patients, regardless of histology. It is administered intravenously on Day 1 of each 3-week cycle. The dose is calculated using the Calvert formula to achieve a target area under the concentration-time curve (AUC) of 5 mg/mL/min. Patients receive 2 cycles of carboplatin in combination with sintilimab (anti-PD-1 antibody) and either pemetrexed (for non-squamous NSCLC) or paclitaxel (for squamous NSCLC). This chemoinmunotherapy phase commences within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.
DRUG	Pemetrexed 500 mg/m2	Pemetrexed is an antifolate chemotherapeutic agent. In this study, it is specifically used for patients with non-squamous non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 500 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of pemetrexed in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. To reduce toxicity risks, standard premedication (including folic acid, vitamin B12 supplementation, and corticosteroids) is required as per the product label. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.
RADIATION	Stereotactic body radiotherapy (SBRT)	Stereotactic Body Radiotherapy (SBRT) is a precise, high-dose form of external beam radiation therapy. In this study, SBRT is directed only at the primary lung tumor (not the lymph nodes). The treatment is delivered in 3 fractions (sessions) over approximately 3 days, with a total dose of 24 Gy (8 Gy per fraction). Treatment planning is based on 4D-CT simulation to account for respiratory motion. The SBRT is completed before the initiation of systemic therapy (sintilimab + chemotherapy).
PROCEDURE	non-small cell lung cancer	Radical lung resection is the planned definitive treatment for eligible patients. Approximately 4 weeks after neoadjuvant therapy, patients first undergo cervical mediastinoscopy for contralateral lymph node assessment. Only those with negative pathology proceed to surgery 2 weeks later. The surgery involves initial video-assisted thoracoscopic dissection of remaining contralateral nodes (specific stations based on primary tumor side) with intraoperative frozen section. If negative, patients undergo immediate repositioning and radical lung resection (lobectomy/pneumonectomy) with ipsilateral lymphadenectomy(right side dissection of lymph nodes in groups 3A, 9R and 10R, left side dissection of lymph nodes in groups 5, 6, 9L and 10L).

Timeline

• Start date: 2025-12-31
• Primary completion: 2027-10-31
• Completion: 2032-10-31
• First posted: 2025-12-30
• Last updated: 2025-12-30