xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05986318</url>
    </required_header>
    <id_info>
      <org_study_id>RESPIRE-ILD</org_study_id>
      <nct_id>NCT05986318</nct_id>
    </id_info>
    <brief_title>Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease</brief_title>
    <acronym>RESPIRE-ILD</acronym>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Lawson Health Research Institute</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>London Health Sciences Centre</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Centre Hospitalier de l'Universite de Montreal (CHUM)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Lawson Health Research Institute</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In this double-blind phase II randomized controlled trial, patients with lung cancer or ≤2&#xD;
        oligometastatic pulmonary lesions and a concomitant diagnosis of ILD who are planned for&#xD;
        radical Radiation Therapy (RT) will be randomized using a 2 x 2 factorial design to oral&#xD;
        N-acetylcysteine (NAC) versus placebo, and also to short course corticosteroids versus&#xD;
        placebo.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Radiation pneumonitis (RP) is the most common and main dose-limiting toxicity after thoracic&#xD;
        RT. RP is characterized histologically by diffuse alveolar damage and acute vascular&#xD;
        permeability induced by direct cytotoxic effect and oxidative stress, leading to the&#xD;
        production of proinflammatory, profibrogenic and proangiogenic cytokines.&#xD;
  &#xD;
        Patients with Interstitial Lung Disease (ILD) are at increased risk of developing lung cancer&#xD;
        compared to the general population. Management of patients with lung cancer in the setting of&#xD;
        a concomitant ILD is complex, as these patients are usually not good candidates for surgery&#xD;
        or immunotherapy. In addition, patients with ILD, particularly fibrotic ILD, are also&#xD;
        reportedly at increased risk of treatment-related toxicity from RT.&#xD;
  &#xD;
        In the present study, investigators will test the following hypotheses:&#xD;
  &#xD;
          1. The use of NAC with RT in patients with underlying ILD will lead to a clinically&#xD;
             meaningful reduction in grade 2-5 dyspnea (as per Common Terminology Criteria for&#xD;
             Adverse Events [CTCAE] version 5.0).&#xD;
  &#xD;
          2. The use of corticosteroids with RT in patients with underlying ILD will lead to a&#xD;
             clinically meaningful reduction in grade 2-5 dyspnea (as per CTCAE version 5.0).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">December 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2032</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2028</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Factorial Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>double-blinded, placebo controlled</masking_description>
    </study_design_info>
    <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</measure>
      <time_frame>Up to 6 months post radiation therapy</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Patient Scored Dyspnea Measured by Visual Analogue Scale (VAS)</measure>
      <time_frame>6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient Scored Cough Measured by Visual Analogue Scale (VAS)</measure>
      <time_frame>6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life Measured by FACIT.org Functional Assessment of Cancer Therapy - Lung (FACT-L) Questionnaire</measure>
      <time_frame>6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Quality of Life Measured by EuroQOL Group EQ-5D-5L Questionnaire</measure>
      <time_frame>6 weeks, 3, 6, 9, 12,18, 24, 36, 48, and 60 months post radiation therapy</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Local Control as Determined by Radiographic Evidence</measure>
      <time_frame>9 years</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival</measure>
      <time_frame>9 years</time_frame>
      <description>Time from enrollment to death from any cause or any progression of disease (local, regional, or distant).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>9 years</time_frame>
      <description>Time from enrollment to death from any cause .</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cancer Specific Survival</measure>
      <time_frame>9 years</time_frame>
      <description>Time from enrollment to death from lung cancer, censored at last follow-up or death from other causes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Radiation Treatment Completion</measure>
      <time_frame>50 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Study Drug Completion Rates</measure>
      <time_frame>50 months</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Participant Unblinding Related to Adverse Events Development</measure>
      <time_frame>50 months</time_frame>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">98</enrollment>
    <condition>Lung Cancer</condition>
    <condition>Interstitial Lung Disease</condition>
    <arm_group>
      <arm_group_label>NAC + Corticosteroids</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will take 600 mg of active NAC orally, three times daily, for 60 days.&#xD;
  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.&#xD;
  All participants will be treated with radical pulmonary radiation therapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Corticosteroids + NAC Placebo</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>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.&#xD;
  Participants will also take matching NAC placebo orally, three times daily, for 60 days.&#xD;
  All participants will be treated with radical pulmonary radiation therapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NAC + Dexamethasone Placebo</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants will take 600 mg of active NAC orally, three times daily, for 60 days.&#xD;
  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.&#xD;
  All participants will be treated with radical pulmonary radiation therapy.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>NAC Placebo + Dexamethasone Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants will take matching NAC placebo orally, three times daily, for 60 days.&#xD;
  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.&#xD;
  All participants will be treated with radical pulmonary radiation therapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>N-Acetyl cysteine</intervention_name>
      <description>NAC capsules</description>
      <arm_group_label>NAC + Corticosteroids</arm_group_label>
      <arm_group_label>NAC + Dexamethasone Placebo</arm_group_label>
      <other_name>NAC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dexamethasone Oral</intervention_name>
      <description>Dexamethasone tablets</description>
      <arm_group_label>Corticosteroids + NAC Placebo</arm_group_label>
      <arm_group_label>NAC + Corticosteroids</arm_group_label>
      <other_name>Corticosteroid</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>N-Acetyl cysteine Placebo</intervention_name>
      <description>Matching placebo for NAC capsules</description>
      <arm_group_label>Corticosteroids + NAC Placebo</arm_group_label>
      <arm_group_label>NAC Placebo + Dexamethasone Placebo</arm_group_label>
      <other_name>NAC Placebo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dexamethasone Placebo</intervention_name>
      <description>Matching placebo for dexamethasone tablets</description>
      <arm_group_label>NAC + Dexamethasone Placebo</arm_group_label>
      <arm_group_label>NAC Placebo + Dexamethasone Placebo</arm_group_label>
      <other_name>Corticosteroid Placebo</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiation Therapy</intervention_name>
      <description>All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.</description>
      <arm_group_label>Corticosteroids + NAC Placebo</arm_group_label>
      <arm_group_label>NAC + Corticosteroids</arm_group_label>
      <arm_group_label>NAC + Dexamethasone Placebo</arm_group_label>
      <arm_group_label>NAC Placebo + Dexamethasone Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Lung cancer or 1-2 oligometastatic pulmonary lesions planned for radical intent&#xD;
               radiotherapy [minimal Biologically Effective Does (BED) of 48 Gy10 (Gray) or&#xD;
               biological equivalent].&#xD;
  &#xD;
            -  Pathologically (histologically or cytologically) proven diagnosis of cancer is not&#xD;
               required, but strongly recommended.&#xD;
  &#xD;
                 -  If the risk of biopsy is unacceptable, pathologic confirmation is not required&#xD;
                    providing there is growth over time on Computed Tomography (CT) imaging and/or&#xD;
                    Fluorodeoxyglucose (FDG) avidity that is strongly suggestive of malignancy.&#xD;
  &#xD;
            -  Fibrotic Interstitial Lung Disease (ILD) of any subtype, as diagnosed by a&#xD;
               respirologist and confirmed by central review&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0-3&#xD;
  &#xD;
            -  Age ≥ 18&#xD;
  &#xD;
            -  Life expectancy &gt; 6 months&#xD;
  &#xD;
            -  Patients are allowed to receive anti-fibrotic agents used in the treatment of&#xD;
               Idiopathic Pulmonary Fibrosis (IPF) or non-IPF fibrotic ILD (e.g. nintedanib,&#xD;
               pirfenidone) and/or corticosteroids, if those are part of their current ILD treatment&#xD;
               regimen. Other immunosuppressive drugs such as mycophenolate, azathioprine,&#xD;
               cyclophosphamide, and rituximab must be stopped for 2 weeks prior and 2 weeks after&#xD;
               Radiation Therapy (RT).&#xD;
  &#xD;
            -  Concurrent standard chemotherapy is allowed where indicated. All other systemic&#xD;
               therapies, including biologic targeted agents or immunotherapy, or any drugs with&#xD;
               known radiosensitive effects, must be stopped for 2 weeks prior and 2 weeks after&#xD;
               treatment.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Prior lung radiotherapy&#xD;
  &#xD;
            -  Plans for the patient to receive other local therapy to the target lesion(s) while on&#xD;
               this study, except at disease progression&#xD;
  &#xD;
            -  Any medical condition that could, in the opinion of the investigator, preclude&#xD;
               radiotherapy or prevent follow-up after radiotherapy&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Contraindications to dexamethasone or N-Acetyl Cysteine (NAC). These include:&#xD;
  &#xD;
                 -  Previous intolerance or allergy to dexamethasone or NAC&#xD;
  &#xD;
                 -  Scleroderma&#xD;
  &#xD;
                 -  Active infection&#xD;
  &#xD;
                 -  Glaucoma&#xD;
  &#xD;
                 -  Psychiatric disorder that could be exacerbated by dexamethasone&#xD;
  &#xD;
                 -  Any other condition that the treating physician believes to be a contraindication&#xD;
                    to dexamethasone or NAC&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>David Palma, MD</last_name>
      <role>Study Chair</role>
      <affiliation>London Health Sciences Centre, Lawson Health Research Institute</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Houda Bahig, MD</last_name>
      <role>Study Chair</role>
      <affiliation>Centre Hospitalier de l'Universite de Montreal</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>David Palma, MD</last_name>
      <phone>519-685-8650</phone>
      <email>david.palma@lhsc.on.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Houda Bahig, MD</last_name>
      <phone>514-890-8254</phone>
      <email>houda.bahig.chum@ssss.gouv.qc.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>London Regional Cancer Program, London Health Sciences Centre</name>
        <address>
          <city>London</city>
          <state>Ontario</state>
          <zip>N6A 5W9</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>David Palma, MD</last_name>
        <phone>519-685-8650</phone>
        <email>David.Palma@lhsc.on.ca</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Centre Hospitalier de l'Universite de Montreal (CHUM)</name>
        <address>
          <city>Montreal</city>
          <state>Quebec</state>
          <zip>H2X 0A9</zip>
          <country>Canada</country>
        </address>
      </facility>
      <investigator>
        <last_name>Houda Bahig, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <reference>
      <citation>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.</citation>
      <PMID>26200274</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>15256622</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>28512460</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>17126203</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>29526532</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>32646918</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>26460792</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>22302051</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>10340042</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>25687856</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>24610080</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 21, 2023</last_update_submitted>
    <last_update_submitted_qc>August 21, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
      <investigator_full_name>David Palma</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Pulmonary Irradiation</keyword>
    <keyword>Radiation Therapy</keyword>
    <keyword>N-Acetyl Cysteine</keyword>
    <keyword>Dexamethasone</keyword>
    <keyword>Radiation Pneumonitis</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Diseases</mesh_term>
      <mesh_term>Lung Diseases, Interstitial</mesh_term>
      <mesh_term>Signs and Symptoms, Respiratory</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Acetylcysteine</mesh_term>
      <mesh_term>Dexamethasone</mesh_term>
      <mesh_term>Dexamethasone acetate</mesh_term>
      <mesh_term>BB 1101</mesh_term>
      <mesh_term>N-monoacetylcystine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05986318
  org study id: RESPIRE-ILD
  nct id: NCT05986318
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  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).
  allocation: Randomized
  intervention model: Factorial Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: double-blinded, placebo controlled
  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
  measure: 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
  description: 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.
  measure: 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
  description: 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.
  measure: 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
  description: 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.
  measure: 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
  description: 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.
  measure: Local Control as Determined by Radiographic Evidence
  time frame: 9 years
  description: 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.
  measure: Progression Free Survival
  time frame: 9 years
  description: Time from enrollment to death from any cause or any progression of disease (local, regional, or distant).
  measure: Overall Survival
  time frame: 9 years
  description: Time from enrollment to death from any cause .
  measure: Cancer Specific Survival
  time frame: 9 years
  description: Time from enrollment to death from lung cancer, censored at last follow-up or death from other causes.
  measure: Rates of Radiation Treatment Completion
  time frame: 50 months
  measure: Rates of Study Drug Completion Rates
  time frame: 50 months
  measure: Rates of Participant Unblinding Related to Adverse Events Development
  time frame: 50 months
  arm group label: NAC + Corticosteroids
  arm group type: Active Comparator
  description: 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.
  arm group label: Corticosteroids + NAC Placebo
  arm group type: Active Comparator
  description: 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.
  arm group label: NAC + Dexamethasone Placebo
  arm group type: Active Comparator
  description: 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.
  arm group label: NAC Placebo + Dexamethasone Placebo
  arm group type: Placebo Comparator
  description: 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.
  intervention type: Dietary Supplement
  intervention name: N-Acetyl cysteine
  description: NAC capsules
  arm group label: NAC + Corticosteroids
  arm group label: NAC + Dexamethasone Placebo
  other name: NAC
  intervention type: Drug
  intervention name: Dexamethasone Oral
  description: Dexamethasone tablets
  arm group label: Corticosteroids + NAC Placebo
  arm group label: NAC + Corticosteroids
  other name: Corticosteroid
  intervention type: Dietary Supplement
  intervention name: N-Acetyl cysteine Placebo
  description: Matching placebo for NAC capsules
  arm group label: Corticosteroids + NAC Placebo
  arm group label: NAC Placebo + Dexamethasone Placebo
  other name: NAC Placebo
  intervention type: Drug
  intervention name: Dexamethasone Placebo
  description: Matching placebo for dexamethasone tablets
  arm group label: NAC + Dexamethasone Placebo
  arm group label: NAC Placebo + Dexamethasone Placebo
  other name: Corticosteroid Placebo
  intervention type: Radiation
  intervention name: Radiation Therapy
  description: All participants will receive radical pulmonary radiation therapy. Conventional techniques or stereotactic ablative radiotherapy will be used.
  arm group label: Corticosteroids + NAC Placebo
  arm group label: NAC + Corticosteroids
  arm group label: NAC + Dexamethasone Placebo
  arm group label: NAC Placebo + Dexamethasone Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: David Palma, MD
  role: Study Chair
  affiliation: London Health Sciences Centre, Lawson Health Research Institute
  last name: Houda Bahig, MD
  role: Study Chair
  affiliation: Centre Hospitalier de l'Universite de Montreal
  last name: David Palma, MD
  phone: 519-685-8650
  email: david.palma@lhsc.on.ca
  last name: Houda Bahig, MD
  phone: 514-890-8254
  email: houda.bahig.chum@ssss.gouv.qc.ca
  facility: 
  contact: 
  facility: 
  investigator: 
  country: Canada
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  citation: 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
  responsible party type: Principal Investigator
  investigator affiliation: Lawson Health Research Institute
  investigator full name: David Palma
  investigator title: Principal Investigator
  mesh term: Lung Diseases
  mesh term: Lung Diseases, Interstitial
  mesh term: Signs and Symptoms, Respiratory
  mesh term: Acetylcysteine
  mesh term: Dexamethasone
  mesh term: Dexamethasone acetate
  mesh term: BB 1101
  mesh term: N-monoacetylcystine
  sharing ipd: No