Inhaled Budesonide for REcurrence Prevention and Adjuvant THerapy in Checkpoint Inhibitor Pneumonitis

The introduction of immune checkpoint inhibitors (immunotherapy) that stimulate our immune system to recognize and attack cancer cells has been one of the most exciting advances in oncology over the last decade. These medications are now employed across almost half of cancer types and settings, however they come with a cost. In some patients, instead of attacking cancer cells alone, the stimulated immune system damages healthy tissues (immune related adverse events), with one of the most severe and potentially deadly such complications being immune attack on the lungs, or checkpoint inhibitor pneumonitis (CIP). When treated promptly with oral or intravenous steroids, acute CIP improves in many cases, however for approximately one-fifth of patients the lung inflammation is difficult to control, resulting in recurrent shortness of breath, the need for extended courses of oral or intravenous steroids, impacting quality of life and cancer therapy decisions. The goal of the trial is to assess whether use of inhaled steroids, a type of medication commonly used in asthma patients, for one year after a first diagnosis of CIP may help the lung inflammation resolve and not return, without the repeated use of oral or intravenous medications that carry more side effects.

Study Overview

• Status: Recruiting
• Conditions: Pneumonitis; Immune-related Adverse Event
• Intervention / Treatment: Other: Arm 1- Usual care; Drug: Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual care

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Abel
• Study Contact Backup: Name: Alexander Watson, MD; Phone Number: 587-231-5098; Email: alexander.watson@cancercarealberta.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Arthur J.E. Child Comprehensive Cancer Centre
      • Contact: Alexander Watson; Email: alexander.watson@cancercarealberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must be 18 years of age, or older on the day of signing informed consent and be willing and able to provide written informed consent/assent and, in the opinion of the Investigator, comply with protocol tests and procedures
2. Patients require histologically confirmed solid tumour undergoing immune checkpoint inhibitor (ICI) therapy

3. Diagnosis of first documented diagnosis of CIP made per ESMO/ASCO guidelines with severity >/grade 2 by CTCAEv5.0, being treated with systemic steroids at time of randomization/enrollment

   a. Per ASCO/ESMO consensus guidelines, evaluation should include a compatible clinical presentation and reasonable exclusion of alternative etiologies, including infection and/or pulmonary disease progression. The extent of infectious workup, including respiratory viral testing, is at the discretion of the treating investigator and should be guided by clinical judgment, and local standards of care. Bronchoscopic sampling is not required but may be considered when clinically indicated.

4. Be able to effectively operate and use budesonide delivery method (Turbuhaler®), either independently or with aid of caregiver who anticipates being able to do so throughout trial period
5. Have adequate organ function, as judged by enrolling clinician
6. Females of childbearing potential have a negative urine or serum pregnancy test prior to study day 1. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses for at least 1 year
7. Females of childbearing potential are willing to use contraception or abstain from heterosexual sexual contact for the course of the study

Exclusion Criteria:

1. Diagnosis of interstitial lung disease (ILD) active (clinically and radiologically evident) within last year prior to diagnosis of CIP
2. Clinically suspected significant lung disease for which inhaled steroid would be standard of care (moderate asthma or severe chronic obstructive pulmonary disease (COPD)) and for which randomization to no inhaled steroids (control arm) would not represent optimal medical care. Based on enrolling physicians judgement; spirometry/pulmonary function tests are NOT required to assess this exclusion criteria.
3. Current (within last two weeks), active (not medically able or unwilling to discontinue prior to treatment start) and regular (2 or more times per week) use of inhaled steroids (for any indication) or systemic (>10mg prednisone equivalent) corticosteroids (for indication other than CIP) at time of randomization
4. Receiving systemic, non-chemotherapy immunosuppressive agent at time of randomization (hydroxychloroquine is acceptable)
5. Use of a medication with significant interaction with inhaled budesonide (HIV protease inhibitors, ketoconazole or other potent CYP3A4 inhibitors), unless deemed required and safe by co-investigator.
6. Known poorly controlled diabetes, defined as A1c >10, prior to initiation of steroids for CIP
7. History of active and unstable systemic disease, including heart failure New York Heart Association (NYHA) III or IV, cirrhosis with Child Pugh B or C, Renal Failure with creatinine clearance (CrCl) <30 per Cockcroft-Gault formula, or other unstable life limiting condition as determined by trial investigators
8. Current or prior participation in a study of an investigational agent or device within 4 weeks of randomization
9. History or current evidence of any condition, therapy, or laboratory abnormalities which might confound trial results, interfere with the patient's participation for the full duration of the trial, or otherwise causing it to be not in the best interest of the patient to participate in the trial, in the opinion of the treating investigator.
10. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is directly involved with this trial, unless prospective ethics board approval (by chair or designee) is given allowing exception to this criterion for a specific patient
11. Breastfeeding is not permitted during the duration of trial participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1- Usual care; The comparison arm will be usual care (UC) for Checkpoint Inhibitor Pneumonitis (CIP); recommended guideline management consists of systemic steroids 1-2mg/kg via oral (grade 2) or IV (grade 3/4) until clinical improvement, then taper over 6 weeks (grade 2) or 8 weeks (grade 3/4). Final CIP management decisions at treating physicians discretion.	Other: Arm 1- Usual care; The comparison arm will be usual care (UC) for Checkpoint inhibitor pneumonitis (CIP) (steroids).; Other Names: Comparator arm
Experimental: Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual care; Budesonide (Pulmicort® Turbuhaler®) 800ug inhaled twice daily (BID) will be taken in addition to usual care for 36 weeks. Checkpoint Inhibitor Pneumonitis (CIP) flare/recurrence will be treated as initial episode/per guidelines.	Drug: Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual care; Budesonide (Pulmicort® Turbuhaler®) 800ug inhaled twice daily (BID) will be taken in addition to usual care for 36 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess efficacy of inhaled budesonide in reducing the development of refractory or recurrent Checkpoint Inhibitor Pneumonitis (RR-CIP) after initial episode of >/grade 2 CIP	Compare incidence of refractory or recurrent Checkpoint inhibitor pneumonitis (RR-CIP) after initial episode of >/grade 2 CIP with or without addition of inhaled budesonide to usual care.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess steroid toxicities after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP)	Frequency of grade 2 or higher steroid toxicities (systemic and local for inhaled) by 36 weeks with or without inhaled budesonide in addition to standard of care in patients after development of >/grade 2 CIP. Safety of intervention will be assessed with this endpoint, but importantly this will also assess any reduction of systemic steroid side effects	1 year
Compare systemic steroids requirements in patients after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP)	Total dose of systemic steroids (mg/kg prednisone equivalents) required by patients at 36 weeks with or without inhaled budesonide after development of >/grade 2 CIP (interim analysis planned). Total dose calculated from start of first systemic steroid taper.	1 year
Assess the impact of adjuvant inhaled budesonide on time to improvement of initial episode of Checkpoint inhibitor pneumonitis (CIP)	Time to symptomatic improvement after initial episode of CIP with or without inhaled budesonide, as assessed by time to improvement by Modified Medical Research Council (mMRC) dyspnea level(s) and Common Terminology Criteria for Adverse Events (CTCAE) v5.0 pneumonitis grade(s).	1 year
Compare Patient Reported Outcomes (PROs) in patients after initial episode of Checkpoint inhibitor pneumonitis (CIP)	Trends of Patient Reported Outcomes (PROs) with or without inhaled budesonide assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) v1.0 at 8 week intervals	1 year

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: March 3, 2025
• First Posted (Actual): March 6, 2025

Study Record Updates

• Last Update Posted (Actual): August 7, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Immune-related Adverse Event; Checkpoint Inhibitor Pneumonitis
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Anti-Inflammatory Agents; Autonomic Agents; Peripheral Nervous System Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Budesonide
• Other Study ID Numbers: IBREATHCIP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No