Pirfenidone Combined With Methylprednisolone Versus Methylprednisolone in the Treatment of CIP

Study Overview
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Brief Summary
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Checkpoint inhibitor-related pneumonitis (CIP）is a common fatal immune-related adverse event of PD-1/PD-L1 inhibitors. Some CIP patients have poor effect on hormone therapy, and the remission time of CIP varies greatly. Antifibrotic drugs may be effective in patients with CIP.

Detailed Description
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Pirfenidone can inhibit the occurrence and development of pulmonary fibrosis, reduce pulmonary exudation by inhibiting VEGF and promote pulmonary recovery. In our study, subjects with checkpoint inhibitor-related pneumonitis receive pirfenidone plus methylprednisolone or methylprednisolone.

Official Title
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Clinical Study of Pirfenidone Combined With Methylprednisolone Versus Methylprednisolone in the Treatment of Checkpoint Inhibitor-related Pneumonitis

Conditions
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Pneumonitis, Malignant Tumor

Intervention / Treatment
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* Drug: Pirfenidone, methylprednisolone
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female who is 18 to 75 years old. Malignant tumors proved by pathology. The subject has received at least one course of immune checkpoint inhibitor treatment. The subject developed grade 3-4 CIP. Take proper contraceptive measures. Appropriate organ system function. Subjects voluntarily participate in this study and sign the informed consent. Exclusion Criteria: Previous treatment with pirfenidone. Clinically significant hemoptysis occurred within 3 months before enrollment (hemoptysis greater than 50ml per day); Or significant clinical bleeding symptoms or clear bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood + + or above, or macrovasculitis. Arteriovenous thrombosis events occurred within 12 months before enrollment, such as cerebrovascular accident, deep venous thrombosis and pulmonary embolism. Abdominal surgery was performed 4 weeks before enrollment, or there was a history of hollow organ perforation. Use nintedanib, cyclophosphamide or cyclosporin within 56 days before enrollment. Suffering from active pulmonary tuberculosis. Patients with mental illness and poor compliance. Sperm / egg donors within 6 months. Lactating women. Persons allergic to pirfenidone. In the investigator's judgment, there are other factors that may have led to the termination of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We randomly divided the patients into two groups and received pirfenidone combined with methylprednisolone or methylprednisolone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Grade 3-4 checkpoint inhibitor-related pneumonitis | Drug: Pirfenidone, methylprednisolone<br>* Methylprednisolone 2 mg / kg / d+ pirfenidone (starting from 200mg tid, increasing to 600mg tid within one week and maintaining) . Methylprednisolone was reduced according to the researcher's evaluation of the patient's condition and the specific course of treatment was determined.<br>|
| Experimental: Control group<br>Grade 3-4 checkpoint inhibitor-related pneumonitis | Drug: Methylprednisolone<br>* Methylprednisolone 2 mg / kg / d . Methylprednisolone was gradually reduced after the improvement of symptoms and imaging. The treatment course was 6-8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degradation time of CIP | According to CTCAE 4.0 and imaging grade of CIP, the time of reduction by one grade was evaluated. | Approximately 3 months | 
| Proportion of degradation within three months | The number of enrollments reduced by grade 1 in 3 months divided by the total number of enrollments. | Approximately 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety(Adverse Events) | Safety will be assessed according to common terminology criteria for adverse events version 4.0 (CTCAE 4.0) | From the day the patient signs informed consent form until 30 days after the last medication | 
| Total amount of hormone | Total amount of methylprednisolone | From the day the patient signs informed consent to the last medication，assessed up to 24 months | 
| MMRC score | Change of Modified Medical Research Council Dyspnea Scale | From the day the patient received treatment until 30 days after the last medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pirfenidone, Methylprednisolone