Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

NCT05986318 | Recruiting Phase 2 DMC

• 1 other identifier: RESPIRE-ILD
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 3

Brief 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 short course corticosteroids versus placebo.

Conditions

Lung Cancer; Interstitial Lung Disease

Keywords

Pulmonary Irradiation; Radiation Therapy; N-Acetyl Cysteine; Dexamethasone; Radiation Pneumonitis

Outcome Measures

Primary Outcomes (1)

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

  Up to 6 months post radiation therapy

Secondary Outcomes (11)

• Patient Scored Dyspnea Measured by Visual Analogue Scale (VAS)

  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)

  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

  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

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

• Local Control as Determined by Radiographic Evidence

  9 years

Study Arms (4)

NAC + Corticosteroids

ACTIVE COMPARATOR

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; Drug: Dexamethasone Oral; Radiation: Radiation Therapy

Corticosteroids + NAC Placebo

ACTIVE COMPARATOR

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; Dietary Supplement: N-Acetyl cysteine Placebo; Radiation: Radiation Therapy

NAC + Dexamethasone Placebo

ACTIVE COMPARATOR

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; Drug: Dexamethasone Placebo; Radiation: Radiation Therapy

NAC Placebo + Dexamethasone Placebo

PLACEBO COMPARATOR

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; Drug: Dexamethasone Placebo; Radiation: Radiation Therapy

Interventions

N-Acetyl cysteine DIETARY_SUPPLEMENT

NAC capsules

Also known as: NAC

NAC + Corticosteroids; NAC + Dexamethasone Placebo

Dexamethasone Oral DRUG

Dexamethasone tablets

Also known as: Corticosteroid

Corticosteroids + NAC Placebo; NAC + Corticosteroids

N-Acetyl cysteine Placebo DIETARY_SUPPLEMENT

Matching placebo for NAC capsules

Also known as: NAC Placebo

Corticosteroids + NAC Placebo; NAC Placebo + Dexamethasone Placebo

Dexamethasone Placebo DRUG

Matching placebo for dexamethasone tablets

Also known as: Corticosteroid Placebo

NAC + Dexamethasone Placebo; NAC Placebo + Dexamethasone Placebo

Radiation Therapy RADIATION

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

Corticosteroids + NAC Placebo; NAC + Corticosteroids; NAC + Dexamethasone Placebo; NAC Placebo + Dexamethasone Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• David Palma: lead
• London Health Sciences Centre: collaborator
• Centre Hospitalier de l'Universite de Montreal (CHUM): collaborator

Study Sites (3)

BC-Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Verspeeten Family Cancer Centre, London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

RECRUITING

Related Publications (11)

• 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.

  PMID: 26200274 BACKGROUND

• 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.

  PMID: 15256622 BACKGROUND

• 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.

  PMID: 28512460 BACKGROUND

• 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.

  PMID: 17126203 BACKGROUND

• 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.

  PMID: 29526532 BACKGROUND

• 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.

  PMID: 32646918 BACKGROUND

• 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.

  PMID: 26460792 BACKGROUND

• 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.

  PMID: 22302051 BACKGROUND

• 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.

  PMID: 10340042 BACKGROUND

• 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.

  PMID: 25687856 BACKGROUND

• 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.

  PMID: 24610080 BACKGROUND

MeSH Terms

Conditions

Lung Neoplasms; Lung Diseases, Interstitial; Radiation Pneumonitis

Interventions

Acetylcysteine; Dexamethasone; Adrenal Cortex Hormones; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Lung Injury; Radiation Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Therapeutics

Study Officials

• David Palma, MD

  London Health Sciences Centre, Lawson Health Research Institute

  STUDY CHAIR

• Houda Bahig, MD

  Centre Hospitalier de l'Universite de Montreal

  STUDY CHAIR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: double-blinded, placebo controlled
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 14, 2023
• Study Start: January 7, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 31, 2032
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)