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AzTrials

Lung CancerPhase 2RESPIRE-ILDNCT05986318

Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

A Phase 2 study testing N-Acetyl cysteine, Dexamethasone Oral and Radiation Therapy in people with Lung Cancer and Interstitial Lung Disease, run by David Palma at 4 sites in Canada.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer, Interstitial Lung Disease
What is being tested?
N-Acetyl cysteine, Dexamethasone Oral and Radiation Therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
98 participants
Where
4 sitesCanada
Study dates
7 Jan 2025to 31 Dec 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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.

Who cannot join

  • 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:
Show all 23Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

David Palma, MD contact

519-685-8650

david.palma@lhsc.on.ca

Houda Bahig, MD contact

514-890-8254

houda.bahig.chum@ssss.gouv.qc.ca

Canada4 sites, 4 recruiting

  • Verspeeten Family Cancer Centre, London Health Sciences Centre

    London, Ontario, N6A 5W9

    David Palma, MD, 519-685-8650, David.Palma@lhsc.on.ca

    Recruiting

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montreal, Quebec, H2X 0A9

    Mom Phat, 514-890-8000 ext. 11171, mom.phat.chum@ssss.gouv.qc.ca

    Siew Siew Pan, 514-890-8000 ext. 22766, siew.siew.pan.chum@ssss.gouv.qc.ca

    Recruiting

  • Saint John Regional Hospital-Horizon Health Network

    Saint John, New Brunswick, E2L4L2

    Robert Thompson, MD, 506-648-6890, robert.thompson2@horizonnb.ca

    Carrie Folkins, RN, 506-648-6890, Carrie.Folkins@HorizonNB.ca

    Recruiting

  • BC-Cancer Agency - Vancouver

    Vancouver, British Columbia, V5Z 4E6

    Sijia (Jackie) Cao, CCRP, 604-877-6000 ext. 672683, sijia.cao@bccancer.bc.ca

    Fermin Hoq, 604-877-6000 ext. 675076, fermin.hoq1@bccancer.bc.ca

    Recruiting

Other trials in Canada

About this study

Official title: 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.

Read the 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).
Being tested
N-Acetyl cysteine, Dexamethasone Oral, N-Acetyl cysteine Placebo, Dexamethasone Placebo, Radiation Therapy
Keywords
Pulmonary Irradiation, Radiation Therapy, N-Acetyl Cysteine, Dexamethasone, Radiation Pneumonitis
Medical subject headings
Lung Neoplasms, Lung Diseases, Interstitial, Radiation Pneumonitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • N-Acetyl cysteineDietary supplement

    Also called NAC

    NAC capsules

  • Dexamethasone OralDrug

    Also called Corticosteroid

    Dexamethasone tablets

  • N-Acetyl cysteine PlaceboDietary supplement

    Also called NAC Placebo

    Matching placebo for NAC capsules

  • Dexamethasone PlaceboDrug

    Also called Corticosteroid Placebo

    Matching placebo for dexamethasone tablets

  • Radiation TherapyRadiation

    All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.

Study groups in NCT05986318
Study groupRoleWhat they receive
NAC + CorticosteroidsActive comparatorParticipants 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.
Receives: Dietary Supplement: N-Acetyl cysteine; Drug: Dexamethasone Oral; Radiation: Radiation Therapy
Corticosteroids + NAC PlaceboActive comparatorParticipants 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.
Receives: Drug: Dexamethasone Oral; Dietary Supplement: N-Acetyl cysteine Placebo; Radiation: Radiation Therapy
NAC + Dexamethasone PlaceboActive comparatorParticipants 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.
Receives: Dietary Supplement: N-Acetyl cysteine; Drug: Dexamethasone Placebo; Radiation: Radiation Therapy
NAC Placebo + Dexamethasone PlaceboPlacebo comparatorParticipants 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.
Receives: Dietary Supplement: N-Acetyl cysteine Placebo; Drug: Dexamethasone Placebo; Radiation: Radiation Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Grade 2-5 Dyspnea within 6 Months Post Radiation Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 5

    Measured: Up to 6 months post radiation therapy

Secondary outcomes (11)

  1. 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.

    Measured: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy

  2. 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.

    Measured: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy

  3. 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.

    Measured: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy

  4. 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.

    Measured: 6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy

  5. 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.

    Measured: 9 years

  6. Progression Free Survival

    Time from enrollment to death from any cause or any progression of disease (local, regional, or distant).

    Measured: 9 years

  7. Overall Survival

    Time from enrollment to death from any cause .

    Measured: 9 years

  8. Cancer Specific Survival

    Time from enrollment to death from lung cancer, censored at last follow-up or death from other causes.

    Measured: 9 years

  9. Rates of Radiation Treatment Completion

    Measured: 50 months

  10. Rates of Study Drug Completion Rates

    Measured: 50 months

  11. Rates of Participant Unblinding Related to Adverse Events Development

    Measured: 50 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start7 Jan 2025
  3. Primary completion1 Jul 2028 (estimated)
  4. Study completion31 Dec 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05986318
Sponsor's protocol ID
RESPIRE-ILD
Acronym
RESPIRE-ILD
Status last verified
Aug 2026
First submitted
1 Aug 2023
Last updated
26 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Verstegen NE, Lagerwaard FJ, Hashemi SM, Dahele M, Slotman BJ, Senan S. Patterns of Disease Recurrence after SABR for Early Stage Non-Small-Cell Lung Cancer: Optimizing Follow-Up Schedules for Salvage Therapy. J Thorac Oncol. 2015 Aug;10(8):1195-200. doi: 10.1097/JTO.0000000000000576.

    PubMed 26200274

  • Choi YW, Munden RF, Erasmus JJ, Park KJ, Chung WK, Jeon SC, Park CK. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics. 2004 Jul-Aug;24(4):985-97; discussion 998. doi: 10.1148/rg.244035160.

    PubMed 15256622

  • Kainthola A, Haritwal T, Tiwari M, Gupta N, Parvez S, Tiwari M, Prakash H, Agrawala PK. Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects. Front Immunol. 2017 May 2;8:506. doi: 10.3389/fimmu.2017.00506. eCollection 2017.

    PubMed 28512460

  • Tsoutsou PG, Koukourakis MI. Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research. Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1281-93. doi: 10.1016/j.ijrobp.2006.08.058.

    PubMed 17126203

  • Niska JR, Schild SE, Rule WG, Daniels TB, Jett JR. Fatal Radiation Pneumonitis in Patients With Subclinical Interstitial Lung Disease. Clin Lung Cancer. 2018 Jul;19(4):e417-e420. doi: 10.1016/j.cllc.2018.02.003. Epub 2018 Feb 17. No abstract available.

    PubMed 29526532

  • Axelsson GT, Putman RK, Aspelund T, Gudmundsson EF, Hida T, Araki T, Nishino M, Hatabu H, Gudnason V, Hunninghake GM, Gudmundsson G. The associations of interstitial lung abnormalities with cancer diagnoses and mortality. Eur Respir J. 2020 Dec 17;56(6):1902154. doi: 10.1183/13993003.02154-2019. Print 2020 Dec.

    PubMed 32646918

  • Ozawa Y, Abe T, Omae M, Matsui T, Kato M, Hasegawa H, Enomoto Y, Ishihara T, Inui N, Yamada K, Yokomura K, Suda T. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer. PLoS One. 2015 Oct 13;10(10):e0140437. doi: 10.1371/journal.pone.0140437. eCollection 2015.

    PubMed 26460792

  • Sanuki N, Ono A, Komatsu E, Kamei N, Akamine S, Yamazaki T, Mizunoe S, Maeda T. Association of computed tomography-detected pulmonary interstitial changes with severe radiation pneumonitis for patients treated with thoracic radiotherapy. J Radiat Res. 2012;53(1):110-6. doi: 10.1269/jrr.110142.

    PubMed 22302051

  • Makimoto T, Tsuchiya S, Hayakawa K, Saitoh R, Mori M. Risk factors for severe radiation pneumonitis in lung cancer. Jpn J Clin Oncol. 1999 Apr;29(4):192-7. doi: 10.1093/jjco/29.4.192.

    PubMed 10340042

  • Lee YH, Kim YS, Lee SN, Lee HC, Oh SJ, Kim SJ, Kim YK, Han DH, Yoo IeR, Kang JH, Hong SH. Interstitial Lung Change in Pre-radiation Therapy Computed Tomography Is a Risk Factor for Severe Radiation Pneumonitis. Cancer Res Treat. 2015 Oct;47(4):676-86. doi: 10.4143/crt.2014.180. Epub 2015 Feb 13.

    PubMed 25687856

  • Yamaguchi S, Ohguri T, Matsuki Y, Yahara K, Oki H, Imada H, Narisada H, Korogi Y. Radiotherapy for thoracic tumors: association between subclinical interstitial lung disease and fatal radiation pneumonitis. Int J Clin Oncol. 2015 Feb;20(1):45-52. doi: 10.1007/s10147-014-0679-1. Epub 2014 Mar 11.

    PubMed 24610080

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-Acetyl cysteine, Dexamethasone Oral and Radiation Therapy in people with Lung Cancer and Interstitial Lung Disease, run by David Palma at 4 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Palma, MD (519-685-8650, david.palma@lhsc.on.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05986318, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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