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

Primary Purpose

Lung Cancer, Interstitial Lung Disease

Status

Not yet recruiting

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

N-Acetyl cysteine

Dexamethasone Oral

N-Acetyl cysteine Placebo

Dexamethasone Placebo

Radiation Therapy

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring Pulmonary Irradiation, Radiation Therapy, N-Acetyl Cysteine, Dexamethasone, Radiation Pneumonitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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 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 Any other condition that the treating physician believes to be a contraindication to dexamethasone or NAC

Sites / Locations

London Regional Cancer Program, London Health Sciences Centre
Centre Hospitalier de l'Universite de Montreal (CHUM)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Arm Label

NAC + Corticosteroids

Corticosteroids + NAC Placebo

NAC + Dexamethasone Placebo

NAC Placebo + Dexamethasone Placebo

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

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.

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.

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.

Progression Free Survival

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

Overall Survival

Time from enrollment to death from any cause .

Cancer Specific Survival

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

Rates of Radiation Treatment Completion

Rates of Study Drug Completion Rates

Rates of Participant Unblinding Related to Adverse Events Development

Full Information

NCT ID

NCT05986318

First Posted

August 1, 2023

Last Updated

August 21, 2023

Sponsor

Lawson Health Research Institute

Collaborators

London Health Sciences Centre, Centre Hospitalier de l'Universite de Montreal (CHUM)

1. Study Identification

Unique Protocol Identification Number

NCT05986318

Brief Title

Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

Acronym

RESPIRE-ILD

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

December 1, 2023 (Anticipated)

Primary Completion Date

July 1, 2028 (Anticipated)

Study Completion Date

December 31, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Lawson Health Research Institute

Collaborators

London Health Sciences Centre, Centre Hospitalier de l'Universite de Montreal (CHUM)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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: 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). 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lung Cancer, Interstitial Lung Disease

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Factorial Assignment

Masking

ParticipantInvestigator

Masking Description

double-blinded, placebo controlled

Allocation

Randomized

Enrollment

98 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

NAC + Corticosteroids

Arm Type

Active Comparator

Arm Description

Arm Title

Corticosteroids + NAC Placebo

Arm Type

Active Comparator

Arm Description

Arm Title

NAC + Dexamethasone Placebo

Arm Type

Active Comparator

Arm Description

Arm Title

NAC Placebo + Dexamethasone Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

N-Acetyl cysteine

Other Intervention Name(s)

NAC

Intervention Description

NAC capsules

Intervention Type

Drug

Intervention Name(s)

Dexamethasone Oral

Other Intervention Name(s)

Corticosteroid

Intervention Description

Dexamethasone tablets

Intervention Type

Dietary Supplement

Intervention Name(s)

N-Acetyl cysteine Placebo

Other Intervention Name(s)

NAC Placebo

Intervention Description

Matching placebo for NAC capsules

Intervention Type

Drug

Intervention Name(s)

Dexamethasone Placebo

Other Intervention Name(s)

Corticosteroid Placebo

Intervention Description

Matching placebo for dexamethasone tablets

Intervention Type

Radiation

Intervention Name(s)

Radiation Therapy

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Patient Scored Dyspnea Measured by Visual Analogue Scale (VAS)

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.

Time Frame

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

Title

Patient Scored Cough Measured by Visual Analogue Scale (VAS)

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.

Time Frame

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

Title

Quality of Life Measured by FACIT.org Functional Assessment of Cancer Therapy - Lung (FACT-L) Questionnaire

Description

Time Frame

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

Title

Quality of Life Measured by EuroQOL Group EQ-5D-5L Questionnaire

Description

Time Frame

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

Title

Local Control as Determined by Radiographic Evidence

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.

Time Frame

9 years

Title

Progression Free Survival

Description

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

Time Frame

9 years

Title

Overall Survival

Description

Time from enrollment to death from any cause .

Time Frame

9 years

Title

Cancer Specific Survival

Description

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

Time Frame

9 years

Title

Rates of Radiation Treatment Completion

Time Frame

50 months

Title

Rates of Study Drug Completion Rates

Time Frame

50 months

Title

Rates of Participant Unblinding Related to Adverse Events Development

Time Frame

50 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

David Palma, MD

Phone

519-685-8650

david.palma@lhsc.on.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Houda Bahig, MD

Phone

514-890-8254

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Palma, MD

Organizational Affiliation

London Health Sciences Centre, Lawson Health Research Institute

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Houda Bahig, MD

Organizational Affiliation

Centre Hospitalier de l'Universite de Montreal

Official's Role

Study Chair

Facility Information:

Facility Name

London Regional Cancer Program, London Health Sciences Centre

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 5W9

Country

Canada

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Palma, MD

Phone

519-685-8650

David.Palma@lhsc.on.ca

Facility Name

Centre Hospitalier de l'Universite de Montreal (CHUM)

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2X 0A9

Country

Canada

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Houda Bahig, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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26200274

Citation

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Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease

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