Pirfenidone Combined With Methylprednisolone Versus Methylprednisolone in the Treatment of CIP

Sponsor

Zhou Chengzhi (Other)

Overall Status

Recruiting

CT.gov ID

NCT05280873

Collaborator

Beijing Continent Pharmaceutical Co, Ltd. (Industry)

Enrollment

Location

Arms

36.3

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonitis Malignant Tumor	Drug: Pirfenidone, methylprednisolone Drug: Methylprednisolone	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

We randomly divided the patients into two groups and received pirfenidone combined with methylprednisolone or methylprednisolone.We randomly divided the patients into two groups and received pirfenidone combined with methylprednisolone or methylprednisolone.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 10, 2021

Anticipated Primary Completion Date :

Oct 20, 2023

Anticipated Study Completion Date :

Oct 20, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group Grade 3-4 checkpoint inhibitor-related pneumonitis	Drug: Pirfenidone, methylprednisolone 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.
Experimental: Control group Grade 3-4 checkpoint inhibitor-related pneumonitis	Drug: Methylprednisolone Methylprednisolone 2 mg / kg / d . Methylprednisolone was gradually reduced after the improvement of symptoms and imaging. The treatment course was 6-8 weeks

Arm

Intervention/Treatment

Experimental: Experimental group

Grade 3-4 checkpoint inhibitor-related pneumonitis

Drug: Pirfenidone, methylprednisolone

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.

Experimental: Control group

Grade 3-4 checkpoint inhibitor-related pneumonitis

Drug: Methylprednisolone

Methylprednisolone 2 mg / kg / d . Methylprednisolone was gradually reduced after the improvement of symptoms and imaging. The treatment course was 6-8 weeks

Outcome Measures

Primary Outcome Measures

Degradation time of CIP [Approximately 3 months]
According to CTCAE 4.0 and imaging grade of CIP, the time of reduction by one grade was evaluated.
Proportion of degradation within three months [Approximately 3 months]
The number of enrollments reduced by grade 1 in 3 months divided by the total number of enrollments.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.