Inhaled Budesonide for REcurrence Prevention and Adjuvant THerapy in Checkpoint Inhibitor Pneumonitis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAHS Cancer Control Alberta
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Patients require histologically confirmed solid tumour undergoing immune checkpoint inhibitor (ICI) therapy
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
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
Disqualifiers
Diagnosis of interstitial lung disease (ILD) active (clinically and radiologically evident) within last year prior to diagnosis of CIP
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.
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
Receiving systemic, non-chemotherapy immunosuppressive agent at time of randomization (hydroxychloroquine is acceptable)
Trial design
Design model
Parallel
Treatments tested in this trial
Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual care
DrugBudesonide (Pulmicort® Turbuhaler®) 800ug inhaled twice daily (BID) will be taken in addition to usual care for 36 weeks.
Arm 1- Usual care
Other interventionThe comparison arm will be usual care (UC) for Checkpoint inhibitor pneumonitis (CIP) (steroids).
Treatment groups
94 Participants
are divided into 2 treatment groupsGroup A: Arm 1- Usual careActive comparator 1 intervention
Group B: Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual careExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
1 yearSecondary outcomes
1
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
Time frame
1 year2
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.
Time frame
1 year3
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).
Time frame
1 year4
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
Time frame
1 yearSponsors and contacts
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Source ClinicalTrials.gov