Reducing respiratory symptoms in lung cancer patients with interstitial lung disease during radiation therapy

Reducing Respiratory Symptoms of Pulmonary Irradiation in Interstitial Lung Disease: A 2x2 Factorial Randomized Phase II Trial Testing N-Acetyl Cysteine and Dexamethasone

This study is testing if a combination of N-acetylcysteine and corticosteroids can help lung cancer patients with interstitial lung disease breathe easier during radiation therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 98 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's (other)
• Drugs / interventions: rituximab, chemotherapy, immunotherapy, Radiation, cyclophosphamide
• Locations: 3 sites (Vancouver, British Columbia and 2 other locations)
• Trial ID: NCT05986318 on ClinicalTrials.gov

What this trial studies

This phase II randomized controlled trial aims to evaluate the effectiveness of N-acetylcysteine and corticosteroids in reducing respiratory symptoms in lung cancer patients who also have interstitial lung disease (ILD) and are undergoing radiation therapy. Patients will be randomly assigned to receive either the active treatments or placebos in a 2 x 2 factorial design. The primary outcome will be the reduction in dyspnea severity, assessed using the Common Terminology Criteria for Adverse Events. The study seeks to address the increased risk of radiation pneumonitis in this vulnerable patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with lung cancer or oligometastatic pulmonary lesions and a diagnosis of fibrotic interstitial lung disease.

Not a fit: Patients without a diagnosis of interstitial lung disease or those with advanced lung cancer not suitable for radiation therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly improve the management of respiratory symptoms in lung cancer patients with ILD, enhancing their quality of life during treatment.

How similar studies have performed: While the approach of using NAC and corticosteroids in this context is novel, previous studies have indicated potential benefits of these agents in managing radiation-induced lung toxicity.

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

Where this trial is running

Vancouver, British Columbia and 2 other locations

• BC-Cancer Agency - Vancouver — Vancouver, British Columbia, Canada (RECRUITING)
• Verspeeten Family Cancer Centre, London Health Sciences Centre — London, Ontario, Canada (RECRUITING)
• Centre Hospitalier de l'Universite de Montreal (CHUM) — Montreal, Quebec, Canada (RECRUITING)

Study contacts

• Study coordinator: David Palma, MD

Conditions: Lung Cancer, Interstitial Lung Disease, Pulmonary Irradiation, Radiation Therapy, N-Acetyl Cysteine, Dexamethasone, Radiation Pneumonitis