Pirfenidone Combined With Methylprednisolone Versus Methylprednisolone in the Treatment of CIP

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

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.

Study Overview

• Status: Recruiting
• Conditions: Malignant Tumor; Pneumonitis
• Intervention / Treatment: Drug: Pirfenidone, methylprednisolone; Drug: Methylprednisolone

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 Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xinqing Lin, Doctor; Phone Number: 13068863939; Email: linxinqing81@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Zhou Chengzhi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female who is 18 to 75 years old.
2. Malignant tumors proved by pathology.
3. The subject has received at least one course of immune checkpoint inhibitor treatment.
4. The subject developed grade 3-4 CIP.
5. Take proper contraceptive measures.
6. Appropriate organ system function.
7. Subjects voluntarily participate in this study and sign the informed consent.

Exclusion Criteria:

1. Previous treatment with pirfenidone.
2. 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.
3. Arteriovenous thrombosis events occurred within 12 months before enrollment, such as cerebrovascular accident, deep venous thrombosis and pulmonary embolism.
4. Abdominal surgery was performed 4 weeks before enrollment, or there was a history of hollow organ perforation.
5. Use nintedanib, cyclophosphamide or cyclosporin within 56 days before enrollment.
6. Suffering from active pulmonary tuberculosis.
7. Patients with mental illness and poor compliance.
8. Sperm / egg donors within 6 months.
9. Lactating women.
10. Persons allergic to pirfenidone.
11. In the investigator's judgment, there are other factors that may have led to the termination of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhou Chengzhi
• Collaborators: Beijing Continent Pharmaceutical Co, Ltd.
• Investigators: Study Director: Chengzhi Zhou, MA, The First Affiliated Hospital of Guangzhou Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 10, 2021
• Primary Completion (ANTICIPATED): October 20, 2023
• Study Completion (ANTICIPATED): October 20, 2024

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: March 6, 2022
• First Posted (ACTUAL): March 15, 2022

Study Record Updates

• Last Update Posted (ACTUAL): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 6, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Pirfenidone; Methylprednisolone
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Pirfenidone
• Other Study ID Numbers: CROC202107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No