Currently, the standard of care treatment for newly diagnosed, inoperable stage III non-small cell lung cancer is radiotherapy (RT) with concurrent chemotherapy, followed by immune checkpoint inhibitors (ICI). RT is a highly effect local treatment. However, high doses of radiation used in curative settings can cause adverse side effects. The most common RT side effect in lung cancer is Radiation Induced Lung Injury (RILI), which can manifest as pneumonitis and/or pulmonary fibrosis. Lung injury can negatively impact patients' well-being and quality of life, and may lead to increased mortality. Risk of lung injury is particularly increased when patients are treated with a combination of treatments (i.e., RT, chemotherapy, and ICI). The drug Pentoxifylline (in combination with α-Tocopherol (Vitamin E)) has been shown to prevent/alter the progression of lung injury and there is a growing body of evidence to support the safety and efficacy of phosphodiesterase inhibitors in cancer treatment. The proposed study aims to determine if the addition of Pentoxifylline, given in combination with α-Tocopherol (Vitamin E), to standard of care treatment will reduce side effects related to lung injury and improve quality of life in this study population.
Female and/or male aged ≥ 18 years.
Histologically confirmed diagnosis of stage III NSCLC, planned for treatment with concurrent chemoradiation and consolidation immune checkpoint inhibitor as per standard of care with no medical contraindications to therapy.
Patients with ECOG performance status 0-2 within 4 weeks of randomization.
Adequate liver function (no evidence of Child-Pugh class C disease or cirrhosis) as per blood work done within 30 days of registration.
Participation in another clinical study with an investigational product during the last 6 months prior to registration.
Patients who will have surgery as part of curative treatment.
Previous radiotherapy to intended treatment volumes in the thorax.
Active pregnancy.
Parallel
Pentoxifylline
DrugPentoxifylline 400 mg orally three times a day and α-Tocopherol IU orally two times a day on day one of radiotherapy and continue treatment for 6 months.
Placebo
Other interventionOne placebo orally three times a day and another placebo orally two times a day on day one of radiotherapy and continue treatment for 6 months.
α-Tocopherol
Other interventionPentoxifylline 400 mg orally three times a day and α-Tocopherol IU orally two times a day on day one of radiotherapy and continue treatment for 6 months.
Change in risk of Lung Injury
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes the risk of lung injury within 12 months post radiotherapy. Lung injury as defined by Grade2+ pneumonitis.
Change in Oncological Outcomes
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes oncological outcomes of progression free survival and overall survival. Progression free survival as measured by RECIST 1.1.
Change in Grade 3-5 treatment related toxicities
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes the incidence of Grade 3-5 treatment (chemoRT + ICI) related toxicity. Grade 3-5 treatment related toxicity measured as per CTCAE version 5.0.
Change in Quality of Life
To evaluate whether the addition of Pentoxifylline and α-Tocopherol changes quality of life, as measured by FACT-LCS (version 4) scores
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University Health Network, Toronto
Lead sponsor
AstraZeneca
Collaborator
