Trial Title:
Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease
NCT ID:
NCT05986318
Condition:
Lung Cancer
Interstitial Lung Disease
Conditions: Official terms:
Lung Diseases
Lung Diseases, Interstitial
Signs and Symptoms, Respiratory
Acetylcysteine
Dexamethasone
Dexamethasone acetate
BB 1101
N-monoacetylcystine
Conditions: Keywords:
Pulmonary Irradiation
Radiation Therapy
N-Acetyl Cysteine
Dexamethasone
Radiation Pneumonitis
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Factorial Assignment
Primary purpose:
Treatment
Masking:
Double (Participant, Investigator)
Masking description:
double-blinded, placebo controlled
Intervention:
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
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:
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).
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
London Regional Cancer Program, London Health Sciences Centre
Address:
City:
London
Zip:
N6A 5W9
Country:
Canada
Contact:
Last name:
David Palma, MD
Phone:
519-685-8650
Email:
David.Palma@lhsc.on.ca
Facility:
Name:
Centre Hospitalier de l'Universite de Montreal (CHUM)
Address:
City:
Montreal
Zip:
H2X 0A9
Country:
Canada
Investigator:
Last name:
Houda Bahig, MD
Email:
Principal Investigator
Start date:
August 1, 2024
Completion date:
December 31, 2032
Lead sponsor:
Agency:
David Palma
Agency class:
Other
Collaborator:
Agency:
London Health Sciences Centre
Agency class:
Other
Collaborator:
Agency:
Centre Hospitalier de l'Universite de Montreal (CHUM)
Agency class:
Other
Source:
Lawson Health Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05986318
