In this double-blind phase II randomized controlled trial, patients with lung cancer or ≤2 oligometastatic pulmonary lesions and a concomitant diagnosis of ILD who are planned for radical Radiation Therapy (RT) will be randomized using a 2 x 2 factorial design to oral N-acetylcysteine (NAC) versus placebo, and also to short course corticosteroids versus placebo.
Radiation pneumonitis (RP) is the most common and main dose-limiting toxicity after thoracic RT. RP is characterized histologically by diffuse alveolar damage and acute vascular permeability induced by direct cytotoxic effect and oxidative stress, leading to the production of proinflammatory, profibrogenic and proangiogenic cytokines. Patients with Interstitial Lung Disease (ILD) are at increased risk of developing lung cancer compared to the general population. Management of patients with lung cancer in the setting of a concomitant ILD is complex, as these patients are usually not good candidates for surgery or immunotherapy. In addition, patients with ILD, particularly fibrotic ILD, are also reportedly at increased risk of treatment-related toxicity from RT. In the present study, investigators will test the following hypotheses: 1. The use of NAC with RT in patients with underlying ILD will lead to a clinically meaningful reduction in grade 2-5 dyspnea (as per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0). 2. The use of corticosteroids with RT in patients with underlying ILD will lead to a clinically meaningful reduction in grade 2-5 dyspnea (as per CTCAE version 5.0).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
98
NAC capsules
Dexamethasone tablets
Matching placebo for NAC capsules
London Regional Cancer Program, London Health Sciences Centre
London, Ontario, Canada
RECRUITINGCentre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, Canada
RECRUITINGRate of Grade 2-5 Dyspnea within 6 Months Post Radiation Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5
Time frame: Up to 6 months post radiation therapy
Patient Scored Dyspnea Measured by Visual Analogue Scale (VAS)
Dyspnea (shortness of breath) severity will be reported by participants via a scale, where a score of 100 is no shortness of breath and a score of 0 is the worst shortness of breath ever.
Time frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
Patient Scored Cough Measured by Visual Analogue Scale (VAS)
Cough severity will be reported by participants via a scale, where a score of 100 is no cough and a score of 0 is the worst cough ever.
Time frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
Quality of Life Measured by FACIT.org Functional Assessment of Cancer Therapy - Lung (FACT-L) Questionnaire
The Functional Assessment of Cancer Therapy - Lung (FACT-L ) is a standardized questionnaire used to measure quality of life. The questionnaire consists of 5 scales measuring 37 items in total. Categories of the 5 scales are: physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns related to symptoms, cognitive function, and regret of smoking. The score for each item in the scale ranges from 0 to 4, where 0 is not at all and 4 is very much. The scores from each scale are added up, and can be combined to provide a total score.
Time frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
Quality of Life Measured by EuroQOL Group EQ-5D-5L Questionnaire
The EQ-5D-5L is a standardized questionnaire used to measure quality of life and health. The first section includes 5 categories: mobility, self-care, usual activities (e.g. work, family), pain/discomfort, and anxiety/depression. Each category contains 5 statements ranging from no problems to extreme problems, where no problems is assigned a code of 1 and extreme problems is assigned a code of 5. Participants are asked to select the statement that best describes their health that day. No score is generated, rather a 5 digit code is generated based on the response provided, which can then be combined into a data set and interpreted in a variety of ways. The second section includes a 20 cm analogue scale from 0 to 100, where 100 is the best health ever imagined and 0 is the worst health imagined. The participant will mark a score on the scale representing the state of their health on that day.
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Matching placebo for dexamethasone tablets
All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.
Time frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
Local Control as Determined by Radiographic Evidence
Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 will be used to measure tumors in the lung (by size), on imaging, to determine how tumors are responding to treatment.
Time frame: 9 years
Progression Free Survival
Time from enrollment to death from any cause or any progression of disease (local, regional, or distant).
Time frame: 9 years
Overall Survival
Time from enrollment to death from any cause .
Time frame: 9 years
Cancer Specific Survival
Time from enrollment to death from lung cancer, censored at last follow-up or death from other causes.
Time frame: 9 years
Rates of Radiation Treatment Completion
Time frame: 50 months
Rates of Study Drug Completion Rates
Time frame: 50 months
Rates of Participant Unblinding Related to Adverse Events Development
Time frame: 50 months