N-Acetyl Cysteine + Corticosteroids for Lung Cancer

(RESPIRE-ILD Trial)

Recruiting at 1 trial location

Overseen By Houda Bahig, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David Palma

Must not be taking: Corticosteroids, NAC

Disqualifiers: Prior lung radiotherapy, Pregnancy, Breastfeeding, Scleroderma, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 60 days

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, N-Acetyl Cysteine (NAC) and corticosteroids (such as Dexamethasone Oral), to determine their effectiveness for patients with lung cancer and interstitial lung disease (a lung condition that causes scarring) undergoing radiation therapy. Participants will receive either NAC, corticosteroids, both, or placebos for each, to compare their effectiveness. Individuals with lung cancer and lung scarring, who plan to undergo radiation and are not currently on certain immune-suppressing medications, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop certain medications. Immunosuppressive drugs like mycophenolate, azathioprine, cyclophosphamide, and rituximab must be stopped for 2 weeks before and after Radiation Therapy. Other systemic therapies, including biologic targeted agents or immunotherapy, must also be stopped for 2 weeks before and after treatment. However, you can continue anti-fibrotic agents and corticosteroids if they are part of your current ILD treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that N-acetyl cysteine (NAC) is generally safe for most adults and has FDA approval for certain uses. Some individuals may experience side effects like nausea or diarrhea, especially at high doses, but many tolerate the 600 mg dose well.

Dexamethasone is commonly used in cancer treatments. The trial uses doses similar to those in regular practice, indicating they are usually safe. However, dexamethasone can cause side effects and is unsafe for pregnant women.

Both treatments have been used before, and the trial uses typical doses. This should reassure participants about their safety in human trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments involving N-Acetyl Cysteine (NAC) combined with corticosteroids for lung cancer because they offer a potentially new approach. Unlike standard chemotherapy and targeted therapies, NAC is known for its antioxidant properties that may help protect lung tissue from damage during radiation therapy. This combination aims to enhance the effectiveness of existing treatments while reducing side effects. The use of NAC, in particular, represents a novel adjunctive strategy that could improve patient outcomes by potentially mitigating the harmful effects of radiation on healthy cells.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research has shown that N-Acetylcysteine (NAC) produces mixed results in cancer treatment. Some studies suggest NAC might extend life, but its specific effect on lung cancer remains unclear. NAC can reduce mucus, potentially aiding breathing, but it might also facilitate the spread of lung cancer. In this trial, some participants will receive NAC with a dexamethasone placebo, while others will receive NAC with active dexamethasone.

Conversely, dexamethasone, a type of steroid, has shown promise for lung cancer patients. Studies have found that dexamethasone can improve treatment response and enhance quality of life. It seems to alleviate symptoms without interfering with other cancer treatments. In this trial, some participants will receive dexamethasone with an NAC placebo, while others will receive dexamethasone with active NAC. ^{1 6 7 8 9}

Who Is on the Research Team?

David Palma, MD

Principal Investigator

London Health Sciences Centre, Lawson Health Research Institute

Houda Bahig, MD

Principal Investigator

Centre Hospitalier de l'Universite de Montreal

Are You a Good Fit for This Trial?

This trial is for adults with lung cancer or up to two small lung tumors and Interstitial Lung Disease (ILD), who are set for radiation therapy. They should be relatively active, have a life expectancy over 6 months, and may continue their ILD treatments like nintedanib or corticosteroids. People can't join if they're allergic to N-Acetyl cysteine or dexamethasone, pregnant, previously had lung radiotherapy, or have certain medical conditions.

Inclusion Criteria

I don't have a confirmed cancer diagnosis, but it's highly suggested.

I have lung cancer or 1-2 small lung tumors and will receive high-dose radiation.

I have been diagnosed with a type of lung scarring disease by a lung specialist.

Exclusion Criteria

I am not allergic to dexamethasone or NAC and do not have conditions like scleroderma, active infections, glaucoma, or certain psychiatric disorders.

I have had radiation therapy for my lung before.

I am not planning to receive other local treatments for my cancer lesions while in this study, unless my disease gets worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Participants receive radical pulmonary radiation therapy

60 days

Daily visits for radiation therapy

Treatment

Participants receive N-acetylcysteine and/or corticosteroids or placebos

60 days

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 months

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

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone Oral
• Dexamethasone Placebo
• N-Acetyl cysteine
• N-Acetyl cysteine Placebo

Trial Overview The study tests whether adding oral N-acetylcysteine (NAC) or short-term corticosteroids reduces respiratory symptoms in patients receiving radiation therapy for lung cancer with ILD. It's a double-blind trial where patients randomly get either the real drugs or placebos alongside their standard treatment.

How Is the Trial Designed?

Group I: NAC + Dexamethasone Placebo Active Control 3 Interventions

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.

Group II: NAC + Corticosteroids Active Control 3 Interventions

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.

Group III: Corticosteroids + NAC Placebo Active Control 3 Interventions

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.

Group IV: NAC Placebo + Dexamethasone Placebo Placebo Group 3 Interventions

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.

Who Is Running the Clinical Trial?

David Palma

Lead Sponsor

Trials

4

Recruited

530+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Centre Hospitalier de l'Universite de Montreal (CHUM)

Collaborator

Trials

1

Recruited

100+

London Health Sciences Centre

Collaborator

Trials

151

Recruited

60,400+

Published Research Related to This Trial

In a study involving 104 chemotherapy-naive ovarian cancer patients, a single high dose of dexamethasone (20 mg) given after cisplatin did not improve control of delayed nausea and vomiting and was associated with increased symptoms compared to placebo.

The findings suggest that dexamethasone may have a 'boomerang effect,' worsening delayed nausea and vomiting, particularly in patients who did not experience acute symptoms, indicating it may not be suitable for managing delayed chemotherapy-induced nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single high-dose dexamethasone improves the effect of ondansetron on acute chemotherapy-induced nausea and vomiting but impairs the control of delayed symptoms. Peterson, C., Hursti, TJ., Börjeson, S., et al.[2019]

Dexamethasone (DEX) has shown potential as an anti-estrogenic agent in treating non-small cell lung cancer (NSCLC), as it significantly suppressed tumor growth in A549 xenograft mice over a 32-day treatment period.

While DEX exhibited mild cytotoxicity to NSCLC cells, it effectively inhibited cell proliferation and increased the expression of estrogen sulfotransferase (EST), leading to reduced estrogen levels in tumors, suggesting a mechanism for its anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone suppresses the growth of human non-small cell lung cancer via inducing estrogen sulfotransferase and inactivating estrogen. Wang, LJ., Li, J., Hao, FR., et al.[2018]

In a Phase 1/2 clinical trial involving 30 patients with advanced non-small cell lung cancer, pretreatment with dexamethasone significantly improved the efficacy of chemotherapy (gemcitabine and carboplatin) by increasing the number of patients who completed the treatment and achieved partial responses.

Dexamethasone also reduced hematopoietic toxicity, as evidenced by improved absolute granulocyte count (AGC) and platelet recovery times, without increasing non-hematologic toxicities, suggesting a safer treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy. Leggas, M., Kuo, KL., Robert, F., et al.[2022]

In a phase III study involving 274 patients with stage IIIA or locally treatable IIIB non-small-cell lung cancer (NSCLC), neoadjuvant docetaxel treatment resulted in a median survival of 14.8 months compared to 12.6 months in the control group, indicating a potential benefit in overall survival.

Docetaxel was well-tolerated, with 77% of patients completing all planned treatment cycles, although it did cause significant side effects like grade 4 neutropenia in 55% of patients, suggesting that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel as neoadjuvant therapy for radically treatable stage III non-small-cell lung cancer: a multinational randomised phase III study. Mattson, KV., Abratt, RP., ten Velde, G., et al.[2020]

In a study of 64 patients undergoing cisplatin-based chemotherapy, high-dose dexamethasone showed a modest antiemetic effect, with a shorter median duration of nausea (0.5 hours) compared to placebo (3.5 hours).

Despite some benefits, only a small percentage of patients (28%) did not vomit with dexamethasone, indicating that its effectiveness as an antiemetic agent is limited in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial. D'Olimpio, JT., Camacho, F., Chandra, P., et al.[2017]

N-acetylcysteine (NAC) significantly reduced the rate of healthcare resource utilization (HCU) events related to COPD exacerbations by 20% compared to placebo, with an even greater reduction of 23% in current and ex-smokers.

In patients using long-acting bronchodilators without inhaled corticosteroids (ICS), NAC led to a remarkable 60% reduction in exacerbation rates compared to those receiving placebo, suggesting NAC could be a beneficial alternative to ICS in certain COPD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of smoking status and concomitant medications on the effect of high-dose N-acetylcysteine on chronic obstructive pulmonary disease exacerbations: A post-hoc analysis of the PANTHEON study. Papi, A., Zheng, J., Criner, GJ., et al.[2020]

In a study of 68 lung cancer patients undergoing cisplatin chemotherapy, dexamethasone (DEX) 16 mg provided complete protection against acute nausea (100% vs. 76.5% in the DEX 8 mg group) and significantly better protection against delayed emesis.

The DEX 16 mg group required less rescue medication for nausea and vomiting, with no severe nausea or vomiting reported, indicating it is a more effective and safe option for managing chemotherapy-induced emesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of dexamethasone 8 mg and 16 mg for the prevention of acute and delayed cisplatin-induced emesis in patients with lung cancer]. Hayakawa, T., Sato, M., Hirohata, T., et al.[2019]

In a randomized, double-blind, placebo-controlled trial involving 100 COPD patients with chronic bronchitis, high-dose N-acetylcysteine (NAC) (900 mg twice daily) did not show significant improvements in respiratory health as measured by the St. George's Respiratory Questionnaire after 3 months.

The study concluded that high-dose NAC does not provide marked clinical benefits for patients suffering from both COPD and chronic bronchitis, indicating that its efficacy in this population may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of N-Acetylcysteine for Chronic Obstructive Pulmonary Disease and Chronic Bronchitis. Zhang, L., Xiong, Y., Du, L.[2023]

In a study comparing breast cancer patients undergoing chemotherapy with and without dexamethasone, those receiving dexamethasone experienced significantly lower rates of nausea and vomiting (p < 0.025).

The findings support the use of dexamethasone as an effective and safe antiemetic during CMF chemotherapy, enhancing patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of dexamethasone as an antiemetic in patients with breast cancer treated with the CMF regimen]. Domaradzka-Woźniak, A., Wojtacki, J., Dziewulska-Bokiniec, A.[2013]

In a phase II trial involving 56 patients with Stage IV non-small cell lung cancer, pre-treatment with dexamethasone (DEX) significantly reduced severe hematologic toxicity from chemotherapy, with lower rates of neutrophil (13% vs. 40%) and platelet (23% vs. 44%) toxicity compared to those not receiving DEX.

Patients receiving DEX also showed trends towards improved response rates and overall survival, suggesting that DEX not only helps in reducing side effects but may also enhance the effectiveness of chemotherapy, although these results were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomized trial of carboplatin and gemcitabine with or without dexamethasone pre-treatment in patients with Stage IV non-small cell lung cancer. Rinehart, J., Arnold, S., Kloecker, G., et al.[2022]

Oral N-acetylcysteine (NAC) significantly reduces the risk of exacerbations in chronic bronchitis patients, with a relative benefit of 1.56 and a number-needed-to-treat of 5.8 based on a systematic review of 11 trials involving 2,011 patients.

NAC also improves symptoms in 61.4% of patients compared to 34.6% in the placebo group, with a relative benefit of 1.78 and a number-needed-to-treat of 3.7, while showing no increase in gastrointestinal adverse effects compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Stey, C., Steurer, J., Bachmann, S., et al.[2019]

In a study of 254 advanced non-squamous NSCLC patients, prophylactic dexamethasone did not significantly affect progression-free survival (PFS) or overall survival when used alongside PD-1 blockade therapy and chemotherapy.

The use of dexamethasone for preventing chemotherapy-associated adverse events (CAAEs) was found to be safe, as it did not lead to increased immune-related adverse effects (irAEs) or negatively impact clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer. Yu, H., Chen, J., Zhou, Y., et al.[2023]

A randomized, controlled trial involving 51 patients with COPD and chronic bronchitis found that high-dose N-acetylcysteine (1,800 mg twice daily) did not improve respiratory health status compared to placebo over 8 weeks.

The study was terminated early due to potential safety concerns, and no significant differences were observed in secondary outcomes related to lung function or inflammation, indicating that high-dose NAC may not be beneficial for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial. Johnson, K., McEvoy, CE., Naqvi, S., et al.[2018]

A meta-analysis of 13 studies involving 4155 COPD patients found that N-acetylcysteine (NAC) significantly reduces the frequency of exacerbations in chronic bronchitis and COPD, with a relative risk of 0.75, indicating a protective effect especially in patients without airway obstruction.

NAC was well tolerated across different doses, and while higher doses (≥ 1200 mg per day) are recommended for patients with airway obstruction, a lower dose (600 mg per day) is effective for those without obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Cazzola, M., Calzetta, L., Page, C., et al.[2022]

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Dexamethasone induces cancer mitigation and irreversible ... DEX treatment leads to permanent senescence in NSCLC cell line. GR level is directly associated with better prognosis of NSCLC patients.

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