Nintedanib in the prevention of radiation-induced lung injury in patients with unresectable stage II-III NSCLC: A protocol for a randomized, multicenter, control group study.

BACKGROUND

Radiation-induced lung injury (RILI) is a common and dose-limiting complication in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy, especially in combination with chemotherapy and/or immunotherapy. RILI encompasses acute radiation pneumonitis (RP) and chronic pulmonary fibrosis, significantly impacting patients' quality of life and treatment outcomes. Preclinical and clinical evidence suggests that nintedanib, a tyrosine kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF), may have preventive effects against RILI due to shared fibrotic pathways. However, prospective data on its prophylactic use remain limited.

METHODS

This is a randomized, multicenter, unblinded, controlled trial designed to evaluate the efficacy and safety of nintedanib in preventing RILI. A total of 66 patients with unresectable stage II-III NSCLC scheduled to receive CCRT will be enrolled from three centers in China. Eligible participants will be randomized 1:1 to either the nintedanib group or the control group. Randomization is stratified by concurrent chemotherapy regimen (etoposide-based vs. taxane-based vs. pemetrexed-based). The nintedanib group will receive oral nintedanib 150 mg twice daily, initiated 1-2 weeks before radiotherapy and continued for 12 weeks, followed by a voluntary treatment period from week 13 to week 24. The control group will receive CCRT alone without nintedanib. All patients will undergo standardized CCRT comprising platinum-based doublet chemotherapy (cisplatin or carboplatin combined with etoposide, taxanes, or pemetrexed) and radiotherapy (60 Gy/30 fractions). Immunotherapy consolidation is permitted as a viable treatment option per guideline recommendations. Primary endpoint: The incidence of grade ≥2 RILI (according to CTCAE v5.0) within 6 months after radiotherapy initiation. Secondary endpoints: Time to radiological lung injury; changes in pulmonary function (FVC%, FEV1%, DLco%); tumor response outcomes (OS, PFS, ORR); safety and tolerability; and patient-reported outcomes. This trial will provide the first prospective evidence on the efficacy of nintedanib for preventing RILI in patients with unresectable stage II-III NSCLC undergoing CCRT. The results may inform clinical practice and guide future prophylactic strategies for RILI.

TRIAL REGISTRATION: This study was registered on April 16, 2025, at the Chinese Clinical Trial Registry (No. ChiCTR2500100845).

REPORTING GUIDELINE: This protocol was developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines.