Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

NCT ID: NCT05986318

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-07

Study Completion Date

2032-12-31

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Lung Cancer Interstitial Lung Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
double-blinded, placebo controlled

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

N-Acetyl cysteine

Intervention Type DIETARY_SUPPLEMENT

NAC capsules

Dexamethasone Oral

Intervention Type DRUG

Dexamethasone tablets

Radiation Therapy

Intervention Type RADIATION

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

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.

Group Type ACTIVE_COMPARATOR

Dexamethasone Oral

Intervention Type DRUG

Dexamethasone tablets

N-Acetyl cysteine Placebo

Intervention Type DIETARY_SUPPLEMENT

Matching placebo for NAC capsules

Radiation Therapy

Intervention Type RADIATION

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

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.

Group Type ACTIVE_COMPARATOR

N-Acetyl cysteine

Intervention Type DIETARY_SUPPLEMENT

NAC capsules

Dexamethasone Placebo

Intervention Type DRUG

Matching placebo for dexamethasone tablets

Radiation Therapy

Intervention Type RADIATION

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

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.

Group Type PLACEBO_COMPARATOR

N-Acetyl cysteine Placebo

Intervention Type DIETARY_SUPPLEMENT

Matching placebo for NAC capsules

Dexamethasone Placebo

Intervention Type DRUG

Matching placebo for dexamethasone tablets

Radiation Therapy

Intervention Type RADIATION

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

Interventions

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N-Acetyl cysteine

NAC capsules

Intervention Type DIETARY_SUPPLEMENT

Dexamethasone Oral

Dexamethasone tablets

Intervention Type DRUG

N-Acetyl cysteine Placebo

Matching placebo for NAC capsules

Intervention Type DIETARY_SUPPLEMENT

Dexamethasone Placebo

Matching placebo for dexamethasone tablets

Intervention Type DRUG

Radiation Therapy

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

Intervention Type RADIATION

Other Intervention Names

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NAC Corticosteroid NAC Placebo Corticosteroid Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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London Health Sciences Centre

OTHER

Sponsor Role collaborator

Centre Hospitalier de l'Universite de Montreal (CHUM)

UNKNOWN

Sponsor Role collaborator

David Palma

OTHER

Sponsor Role lead

Responsible Party

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David Palma

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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David Palma, MD

Role: STUDY_CHAIR

London Health Sciences Centre, Lawson Health Research Institute

Houda Bahig, MD

Role: STUDY_CHAIR

Centre Hospitalier de l'Universite de Montreal

Locations

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London Regional Cancer Program, London Health Sciences Centre

London, Ontario, Canada

Site Status RECRUITING

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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David Palma, MD

Role: CONTACT

519-685-8650

Houda Bahig, MD

Role: CONTACT

514-890-8254

Facility Contacts

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David Palma, MD

Role: primary

519-685-8650

Mom Phat

Role: primary

514-890-8000 ext. 11171

Siew Siew Pan

Role: backup

514-890-8000 ext. 22766

References

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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.

Reference Type BACKGROUND
PMID: 26200274 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15256622 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28512460 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17126203 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29526532 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32646918 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26460792 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22302051 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10340042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25687856 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24610080 (View on PubMed)

Other Identifiers

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RESPIRE-ILD

Identifier Type: -

Identifier Source: org_study_id

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