Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease (RESPIRE-ILD)

March 6, 2026 updated by: David Palma

Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease: A 2x2 Factorial Randomized Phase II Trial Testing N-Acetyl Cysteine and Dexamethasone

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Estimated)

98

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • BC-Cancer Agency - Vancouver
        • Contact:
        • Contact:
        • Principal Investigator:
          • Srinivas Raman, MD,FRCPC
    • Ontario
      • London, Ontario, Canada, N6A 5W9
        • Recruiting
        • Verspeeten Family Cancer Centre, London Health Sciences Centre
        • Contact:
    • Quebec
      • Montreal, Quebec, Canada, H2X 0A9

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Lung cancer or 1-2 oligometastatic pulmonary lesions planned for radical intent radiotherapy [minimal Biologically Effective Does (BED) of 48 Gy10 (Gray) or biological equivalent].

  • Pathologically (histologically or cytologically) proven diagnosis of cancer is not required, but strongly recommended.

    • If the risk of biopsy is unacceptable, pathologic confirmation is not required providing there is growth over time on Computed Tomography (CT) imaging and/or Fluorodeoxyglucose (FDG) avidity that is strongly suggestive of malignancy.
  • Fibrotic Interstitial Lung Disease (ILD) of any subtype, as diagnosed by a respirologist and confirmed by central review
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-3
  • Age ≥ 18
  • Life expectancy > 6 months
  • Patients are allowed to receive anti-fibrotic agents used in the treatment of Idiopathic Pulmonary Fibrosis (IPF) or non-IPF fibrotic ILD (e.g. nintedanib, pirfenidone) and/or corticosteroids, if those are part of their current ILD treatment regimen. Other immunosuppressive drugs such as mycophenolate, azathioprine, cyclophosphamide, and rituximab must be stopped for 2 weeks prior and 2 weeks after Radiation Therapy (RT).
  • Concurrent standard chemotherapy is allowed where indicated. All other systemic therapies, including biologic targeted agents or immunotherapy, or any drugs with known radiosensitive effects, must be stopped for 2 weeks prior and 2 weeks after treatment.

Exclusion Criteria:

  • Prior lung radiotherapy
  • Current use of oral or intravenous corticosteroids
  • Plans for the patient to receive other local therapy to the target lesion(s) while on this study, except at disease progression
  • Any medical condition that could, in the opinion of the investigator, preclude radiotherapy or prevent follow-up after radiotherapy

  • Pregnancy

    • If not pregnant, use of effective contraception methods for women of childbearing age is required which can include:

      • hormonal methods (e.g. oral, injected, implanted),
      • placement of an intrauterine device,
      • barrier methods (i.e. condoms),
      • sterilization of the partner (e.g. previous vasectomy)
      • abstinence
    • Women who become pregnant should stop taking NAC and/or dexamethasone and inform their study doctor.
    • Male participants should use adequate forms of birth control with their partners.
  • Currently breastfeeding
  • Current or recent use of NAC

  • Contraindications to dexamethasone or N-Acetyl Cysteine (NAC). These include:

    • Previous intolerance or allergy to dexamethasone or NAC
    • Scleroderma
    • Active infection
    • Glaucoma
    • Psychiatric disorder that could be exacerbated by dexamethasone
    • Cystinuria
    • Any other condition that the treating physician believes to be a contraindication to dexamethasone or NAC

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: NAC + Corticosteroids

Participants will take 600 mg of active NAC orally, three times daily, for 60 days.

Participants will also take 4 mg of active dexamethasone, orally, once daily for 10 days, then 2 mg, orally, once daily for 5 days, then 1 mg, orally, once daily for 5 days.

All participants will be treated with radical pulmonary radiation therapy.
Dietary supplement: N-Acetyl cysteine
NAC capsules
Other Names:
  • NAC
Drug: Dexamethasone Oral
Dexamethasone tablets
Other Names:
  • Corticosteroid
Radiation: Radiation Therapy
All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.
Active Comparator: Corticosteroids + NAC Placebo

Participants will take 4 mg of active dexamethasone, orally, once daily for 10 days, then 2 mg, orally, once daily for 5 days, then 1 mg, orally, once daily for 5 days.

Participants will also take matching NAC placebo orally, three times daily, for 60 days.

All participants will be treated with radical pulmonary radiation therapy.
Drug: Dexamethasone Oral
Dexamethasone tablets
Other Names:
  • Corticosteroid
Dietary supplement: N-Acetyl cysteine Placebo
Matching placebo for NAC capsules
Other Names:
  • NAC Placebo
Radiation: Radiation Therapy
All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.
Active Comparator: NAC + Dexamethasone Placebo

Participants will take 600 mg of active NAC orally, three times daily, for 60 days.

Participants will also take matching dexamethasone placebo (4 mg for 10 days, then 2 mg for 5 days, then 1 mg for 5 days), orally, once daily.

All participants will be treated with radical pulmonary radiation therapy.
Dietary supplement: N-Acetyl cysteine
NAC capsules
Other Names:
  • NAC
Drug: Dexamethasone Placebo
Matching placebo for dexamethasone tablets
Other Names:
  • Corticosteroid Placebo
Radiation: Radiation Therapy
All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.
Placebo Comparator: NAC Placebo + Dexamethasone Placebo

Participants will take matching NAC placebo orally, three times daily, for 60 days.

Participants will also take matching dexamethasone placebo (4 mg for 10 days, then 2 mg for 5 days, then 1 mg for 5 days), orally, once daily.

All participants will be treated with radical pulmonary radiation therapy.
Dietary supplement: N-Acetyl cysteine Placebo
Matching placebo for NAC capsules
Other Names:
  • NAC Placebo
Drug: Dexamethasone Placebo
Matching placebo for dexamethasone tablets
Other Names:
  • Corticosteroid Placebo
Radiation: Radiation Therapy
All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate 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
Up to 6 months post radiation therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: 9 years
Time from enrollment to death from any cause or any progression of disease (local, regional, or distant).
9 years
Overall Survival
Time Frame: 9 years
Time from enrollment to death from any cause .
9 years
Cancer Specific Survival
Time Frame: 9 years
Time from enrollment to death from lung cancer, censored at last follow-up or death from other causes.
9 years
Rates of Radiation Treatment Completion
Time Frame: 50 months
50 months
Rates of Study Drug Completion Rates
Time Frame: 50 months
50 months
Rates of Participant Unblinding Related to Adverse Events Development
Time Frame: 50 months
50 months
Patient Scored Dyspnea Measured by Visual Analogue Scale (VAS)
Time Frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
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.
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)
Time Frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
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.
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
Time Frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
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.
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
Time Frame: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
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.
6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy
Local Control as Determined by Radiographic Evidence
Time Frame: 9 years
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.
9 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Palma

Collaborators

Centre hospitalier de l'Université de Montréal (CHUM)
London Health Sciences Centre

Investigators

  • Study Chair: David Palma, MD, London Health Sciences Centre, Lawson Health Research Institute
  • Study Chair: Houda Bahig, MD, Centre Hospitalier de l'Université de Montréal

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 7, 2025

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

December 31, 2032

Study Registration Dates

First Submitted

August 1, 2023

First Submitted That Met QC Criteria

August 1, 2023

First Posted (Actual)

August 14, 2023

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 6, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RESPIRE-ILD

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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