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NOT YET RECRUITING
NCT07388680
PHASE2/PHASE3

Pirfenidone Capsules in the Treatment of Radiation-induced Lung Injury With or Without Immune Pneumonia

Sponsor: Beijing Continent Pharmaceutical Co, Ltd.

View on ClinicalTrials.gov

Summary

Radiation-induced lung injury (RILI) is one of the most common thoracic-radiotherapy complications, with an incidence as high as 31.4 %. Multiple studies have shown that RILI can adversely affect patient prognosis by disrupting treatment schedules. Moreover, the widespread clinical use of immune-checkpoint inhibitors (ICIs) has further increased pulmonary toxicity when radiotherapy (RT) is combined with ICIs. Checkpoint-inhibitor-related pneumonitis (CIP)-i.e., immune-mediated lung injury-may necessitate permanent discontinuation of ICIs, diminish survival benefit, and, in severe cases, directly threaten life. The diagnosis of both RILI and CIP is based on an integrated assessment of subjective symptoms and imaging findings.RILI typically occurs 1-3 months after completion of radiotherapy, whereas CIP may emerge at any point during treatment. The two entities share similar clinical presentations: fever, dry cough, chest tightness, dyspnoea, and pleuritic chest pain. Computed tomography (CT) is the most sensitive imaging modality. Pulmonary-function testing is another routinely used clinical metric; vital capacity, total lung capacity, forced expiratory volume in 1 s (FEV₁), and diffusing capacity of the lung for carbon monoxide (DLCO) may all decline, with DLCO being the most sensitive parameter. In advanced cases, arterial oxygen and carbon-dioxide tensions may also deteriorate.Currently, RILI is managed empirically with systemic corticosteroids and supportive care; however, this approach yields limited improvement in diffusing capacity or ventilatory function, and its ability to prevent radiation-induced pulmonary fibrosis (RPF) remains undefined. Corticosteroids also remain the mainstay of CIP therapy. Pirfenidone, a potent cytokine inhibitor, attenuates fibroblast activity by reducing production of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), thereby suppressing fibroblast proliferation and extracellular-matrix collagen synthesis. Pre-clinical efficacy studies have demonstrated robust anti-inflammatory, anti-oxidant, and anti-fibrotic effects in the lung.Because RILI and pneumonitis arising from combined radio-immunotherapy are often indistinguishable in clinical practice, and because both share pathogenetic features with idiopathic pulmonary fibrosis (IPF), the investigators initiated this phase II/III trial to address the unmet medical need for effective therapy. Building on prior pre-clinical and clinical data, the study aims to establish the optimal dose of pirfenidone capsules for RILI with or without concomitant CIP and to confirm efficacy and safety.Phase II (dose-finding): The study consists of a screening period (Day -28 to Day -1), a 168-day treatment-observation period (Day 1-Day 168), a safety follow-up (28 ± 7 days after the last dose), and subsequent disease-progression and survival follow-up. Ninety subjects with RILI, with or without CIP, who meet all eligibility criteria will be randomly assigned 1:1:1 to low-dose pirfenidone (400 mg TID), high-dose pirfenidone (600 mg TID), or matching placebo.Phase III (confirmatory): The dose of pirfenidone capsules for phase III will be determined jointly by the sponsor and investigators based on accumulated efficacy and safety data. The trial structure mirrors phase II: screening (Day -28 to Day -1), 168-day treatment-observation (Day 1-Day 168), safety follow-up (28 ± 7 days after the last dose), and disease-progression and survival follow-up. Eligible subjects with RILI ± CIP will be randomized 1:1 to receive either pirfenidone capsules (400 mg or 600 mg TID, taken with meals) or identical placebo. After completion of the 28-day post-treatment follow-up, all phase III participants will enter an extension phase for long-term survival assessment every 3 months (± 7 days).This trial will investigate the progression-free survival (PFS) and overall survival (OS) associated with pirfenidone capsules in patients with Grade 2 and 3 radiation-induced lung injury (RILI), with or without chemotherapy-induced pneumonitis (CIP).

Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase II/III Clinical Trial on the Efficacy and Safety of Pirfenidone Capsules in the Treatment of Radiation-induced Lung Injury With or Without Immune-related Pneumonia

Key Details

Gender

All

Age Range

18 Years - 75 Years

Study Type

INTERVENTIONAL

Enrollment

298

Start Date

2026-02-28

Completion Date

2026-10-30

Last Updated

2026-02-17

Healthy Volunteers

No

Interventions

DRUG

Pirfenidone Capsules (400 mg)

Low-dose group:400 mg, TID

DRUG

Pirfenidone Capsules(600mg)

Pirfenidone Capsules(600mg,TID)

DRUG

Pirfenidone Capsules(0mg)

Placebo(0mg,TID)

Locations (36)

Anhui Provincial Chest Hospital

Hefei, Anhui, China

Chinese Academy of Medical Sciences Cancer Hospital

Beijing, Beijing Municipality, China

Affiliated Hospital of Fujian Medical University, Xiehe Branch

Fuzhou, Fujian, China

Fujian Provincial Cancer Hospital

Fuzhou, Fujian, China

Lanzhou University First Hospital

Lanzhou, Gansu, China

Foshan First Hospital

Foshan, Guangdong, China

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Panyu Central Hospital Affiliated to Guangzhou Medical University

Guangzhou, Guangdong, China

Southern Medical University - Southern Hospital

Guangzhou, Guangdong, China

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

The First Affiliated Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, China

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China

Gaozhou People's Hospital

Maoming, Guangdong, China

Chinese Academy of Medical Sciences Cancer Hospital Shenzhen Branch

Shenzhen, Guangdong, China

Shenzhen People's Hospital

Shenzhen, Guangdong, China

Affiliated Hospital of Guangdong Medical UniversityAffiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, China

Zhongshan People's Hospital

Zhongshan, Guangdong, China

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

The Second Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

Hebei University Affiliated Hospital

Baoding, Hebei, China

Anyang City Cancer Hospital

Anyang, Henan, China

Henan Provincial Cancer Hospital

Zhengzhou, Henan, China

Hubei Provincial Cancer Hospital

Wuhan, Hubei, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Xuzhou Medical University Affiliated Hospital

Xuzhou, Jiangsu, China

Gansu Provincial Cancer Hospital

Gansu, Lanzhou, China

Jining First People's Hospital

Jining, Shandong, China

Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, China

Shanghai Chest HospitalShanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Sichuan Provincial Cancer Hospital

Chengdu, Sichuan, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Hunan Provincial Cancer HospitalHunan Provincial Cancer Hospital

Changsha, Wuhan, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Zhejiang Provincial Cancer HospitalZhejiang Provincial Cancer Hospital

Hangzhou, Zhejiang, China

Taizhou Cancer Hospital

Taizhong, Zhejiang, China