Inhaled Budesonide for REcurrence Prevention and Adjuvant THerapy in Checkpoint Inhibitor Pneumonitis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
- •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
- •Have adequate organ function, as judged by enrolling clinician
- •Females of childbearing potential have a negative urine or serum pregnancy test prior to study day
- •Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses for at least 1 year
- •Females of childbearing potential are willing to use contraception or abstain from heterosexual sexual contact for the course of the study
排除标准
- •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)
- •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.
- •Known poorly controlled diabetes, defined as A1c >10, prior to initiation of steroids for CIP
- •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
- •Current or prior participation in a study of an investigational agent or device within 4 weeks of randomization
- •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.
- •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
- •Breastfeeding is not permitted during the duration of trial participation.
研究组 & 干预措施
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.
干预措施: Arm 2- Budesonide (Pulmicort® Turbuhaler®) + Usual care (Drug)
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.
干预措施: Arm 1- Usual care (Other)
结局指标
主要结局
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
时间窗: 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.
次要结局
- Assess steroid toxicities after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP)(1 year)
- Compare systemic steroids requirements in patients after development of >/grade 2 Checkpoint inhibitor pneumonitis (CIP)(1 year)
- Assess the impact of adjuvant inhaled budesonide on time to improvement of initial episode of Checkpoint inhibitor pneumonitis (CIP)(1 year)
- Compare Patient Reported Outcomes (PROs) in patients after initial episode of Checkpoint inhibitor pneumonitis (CIP)(1 year)