Immune-related Adverse Event, Pneumonitis
Conditions
Keywords
Immune-related Adverse Event, Checkpoint Inhibitor Pneumonitis
Brief summary
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.
Interventions
DRUGArm 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.
OTHERArm 1- Usual care
The comparison arm will be usual care (UC) for Checkpoint inhibitor pneumonitis (CIP) (steroids).
Sponsors
AHS Cancer Control Alberta
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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. The comparison arm will be usual care (UC) for CIP; recommended guideline management consists of systemic steroids 1-2mg/kg via oral (grade 2) or intravenous (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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess steroid toxicities after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP) | 1 year | 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 |
| Compare systemic steroids requirements in patients after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP) | 1 year | 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. |
| Assess the impact of adjuvant inhaled budesonide on time to improvement of initial episode of Checkpoint inhibitor pneumonitis (CIP) | 1 year | 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). |
| Compare Patient Reported Outcomes (PROs) in patients after initial episode of Checkpoint inhibitor pneumonitis (CIP) | 1 year | 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 |
Countries
Canada
Contacts
CONTACTAlexander Watson, MD
CONTACTAmy Abel
Outcome results
None listed