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About
This phase II trial tests whether oral iloprost works in preventing lung cancer (chemoprevention) in former smokers. Oral iloprost has previously been shown to reduce abnormal lung cells in former smokers, suggesting a clinically significant impact on lung cancer risk. The use of oral iloprost may help keep cancer from forming and reduce abnormal cells in the lung in order to lower the risk of developing lung cancer in former smokers.
Full description
PRIMARY OBJECTIVE:
I.To determine if oral iloprost, starting at 50 ug twice daily (BID) and increased monthly to a final dose of 150 ug BID as tolerated, compared to placebo for 6 months is effective in reducing endobronchial dysplasia in former smokers who have mild or worse dysplasia on an endobronchial biopsy at baseline bronchoscopy.
SECONDARY OBJECTIVES:
I. To determine if treatment with oral iloprost compared to placebo results in a change in average dysplasia (over all sites of mild or greater dysplasia).
II. To determine safety of treatment with oral iloprost.
EXPLORATORY OBJECTIVES:
I. To determine if treatment with oral iloprost compared to placebo results in a change in response rate defined as >= 1 point reduction in maximum dysplasia.
II. To determine if the in vitro differentiation response of bronchial epithelial cell progenitors cultured at the air liquid interface is predictive of the in vivo response of dysplasia improvement (to be done only in participants recruited in Colorado).
III. To determine if treatment with oral iloprost compared to placebo results in a decrease in the volume of pure ground glass opacities (GGOs) on chest computed tomography (CT).
IV. To determine if treatment with oral iloprost compared to placebo increases peripheral lung epithelial progenitor counts, measured by organoid formation in a three dimensional culture system seeded from distal airway brushings (to be done only in participants recruited in Colorado).
V. To determine if oral iloprost reduces the incidence of lung cancer compared to placebo.
VI. To evaluate the ability of 3-dimensional morphologic analysis of expectorated sputum by LuCED compared to standard sputum cytopathology to predict endobronchial dysplasia and measure response to iloprost.
VII. To evaluate histologic response by alternative criteria.
OUTLINE: Patients are randomized in 1 of 2 arms.
ARM I: Patients receive iloprost orally (PO) BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
ARM II: Patients receive iloprost placebo PO BID for a 180 days in the absence of unacceptable toxicity. Patients undergo bronchoscopy with biopsies and brushings at day 180.
After completion of study treatment, patients are followed up for 30 days.
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Inclusion criteria
Participants must be former smokers (> 12 months abstinent and confirmed by serum cotinine) with at least a 30 pack-year cigarette history who are at high risk for the development of lung cancer with at least one of the following:
Participants must be able to safely undergo bronchoscopy in the judgement of the investigator
Participants must have a biopsy showing mild (grade 4 on WHO score) or greater dysplasia on the baseline bronchoscopy
Participants must be at least 50 years old. Because no dosing or adverse event (AE) data are currently available on the use of iloprost in participants <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Leukocytes >= 3,000/microliter
Platelets >= 100,000/microliter
Total bilirubin =< 2.0 mg/dl
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (ULN)
Creatinine =< 2.0 mg/dl
The effects of iloprost on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because prostacyclins are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
Primary purpose
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0 participants in 2 patient groups, including a placebo group
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Data sourced from clinicaltrials.gov
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