The following datasets contain the data available for EPPT NWU2013-02-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 34 datasets contain the raw form data received, excluding PII.

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Trial Summary

This randomized phase I clinical trial studied the side effects and the best dose of inhalational iloprost in preventing lung cancer in former smokers. Inhaled iloprost may help prevent lung cancer from forming in former smokers who have had abnormal cells found in their mucus.

The inhaled iloprost was administered for 60 days either 2 or 4 times a day depending on cohort.

Patients are randomized to 1 of 2 treatment arms in 1 of 2 cohorts (4 arms total):

• Cohort A
  • ARM I: Iloprost via inhalation using a nebulizer 4 times a day for 60 days
  • ARM II: Placebo via inhalation using a nebulizer 4 times a day for 60 days
• Cohort B
  • ARM III: Iloprost via inhalation using a nebulizer 2 times a day for 60 days
  • ARM IV: Placebo via inhalation using a nebulizer 2 times a day for 60 days

Enrollment Statistics

Target Enrollment: 60

Actual Enrollment: 34

Actual Registration: 69

• 34 people randomized
  • 27 in Arm I (27 out of 34 randomized): 4x a day iloprost
    • 23 completed the study.
    • 2 withdrew from study.
    • 1 dropped due to adverse events.
    • 1 dropped due to other reasons.
  • 1 in Arm II (1 out of 34 randomized): 4x a day Placebo
    • 1 completed the study
  • 5 in Arm III (5 out of 34 randomized): 2x a day iloprost
    • 3 completed the study
    • 2 dropped due to adverse events.
  • 2 in Arm IV (2 out of 34 randomized): 2x a day Placebo
    • 2 completed the study
• 35 people were not randomized (35 of 69 registered)

Statistical Analysis and Total Study Population Demographics:

• Age (years):
  • Mean: 64.8
  • Range: 32-84
  • Median: 67
• Height (cm):
  • Mean: 175.5
  • IQR: 170-183
  • Range: 154-193
  • Median: 175.9
• Weight (kg):
  • Mean: 94
  • IQR: 85-104
  • Range: 52-143
  • Median: 93.1
• Gender:
  • Male: 30 (91.5%)
  • Female: 4 (8.5%)

Eligibility Criteria

Inclusion Criteria

• Participants must have either sputum cytologic atypia of mild dysplasia or greater or a history of bronchial biopsy with mild or greater dysplasia within the past 12 months
• Participants must have a smoking history of 20 pack-years or greater
• Participants must have the ability to safely undergo bronchoscopy in the judgment of the investigators
• Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
• Leukocytes >= 3,000/microliter
• Platelets >= 100,000/microliter
• Total bilirubin =< 2.0 mg/dl
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 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 having intercourse with a woman of childbearing potential 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; Note: Women are considered to be of child-bearing potential if they are not surgically sterile or are under the age of 65 and have menstruated within the last two years
• Participants must be able to understand and willing to sign a written informed consent document

Exclusion Criteria

• Participants must not have used any tobacco product in the past year
• Participants must not be currently receiving or have previously received thiazolidinedione treatment unless sputum atypia or endobronchial dysplasia are documented again after thiazolidinedione treatment and within 12 months of entry
• Participants must not have been treated with iloprost at any time; Note: participants on the placebo arm of previous iloprost trials are eligible, but participants on the placebo arm of cohort A of this study may not be enrolled in cohort B
• Participants must not have used any other investigation agent within the last six months
• Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition of iloprost
• Participants must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the opinion of investigators would jeopardize patient safety of data integrity; Note: individuals who are human immunodeficiency virus (HIV) positive will not necessarily be excluded, will be considered on a case-by-case basis, but will be required to meet criteria related to patient safety and data integrity, as assessed by investigators
• Participants must not have a current or prior invasive malignancy within the past 6 months; participants may enroll prior to biopsy result report, unless there are findings at bronchoscopy suggesting an invasive malignancy; history of the following curatively treated cancers during any time prior to screening is allowed: non-melanoma skin cancer, cervical carcinoma in situ, and bladder carcinoma in situ
• Participants must not have received either chemotherapy or radiotherapy within the previous 6 months; Note: participants receiving long-term adjuvant hormonal therapy (such as tamoxifen or aromatase inhibitors for breast cancer) are allowed
• Women must not be pregnant or breastfeeding; iloprost is a prostacyclin agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with iloprost, breastfeeding should be discontinued if the mother is treated with iloprost
• As iloprost inhibits platelet function, patients must not be taking anticoagulants, with the exception of aspirin or other non-steroidal anti-inflammatory medications
• Due to risk for hypotension in patients on vasodilators or antihypertensive medications, participants must not have blood pressure < 95 mm Hg systolic

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

Results/Findings:

Following sputum cytology and inclusion/exclusion review at pre-screening, participants were evaluated at baseline by conducting their physical exam, recording their medical and surgical histories, baseline symptoms, concomitant medications, sputum cytologies, and collection of blood information. Participants were then registered and randomized in either of the two cohorts with a placebo and iloprost arm within each. Cohorts were split to either taking the study agent 2 or 4 times per day for 60 days. Participant had a phone call at day 15 to review concomitant medications and assess toxicity. At visit 2 (day 30), visit 3 (day 60), and visit 4 (day 90) participants had their physical exam conducted, had vital signs taken, concomitant medications reviewed, performance status and toxicity assessed, lab studies performed, and answered questionnaires and smoking status. After day 90, follow-up continued until the resolution of all toxicities and then annually for up to 5 years after the study ended.