A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
Overview
- Phase
- Phase 2
- Intervention
- iloprost
- Conditions
- Lung Cancer
- Sponsor
- University of Colorado, Denver
- Enrollment
- 152
- Locations
- 6
- Primary Endpoint
- Change in Average (Follow-up - Baseline) From All Biopsies
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Iloprost may be effective in preventing lung cancer.
PURPOSE: This randomized phase II trial is studying how well iloprost works in preventing lung cancer in patients who are at high risk for this disease.
Detailed Description
OBJECTIVES: Primary * Compare the reversal of premalignant histological changes in the bronchial epithelium of patients at high risk for lung cancer (defined by \> 20 pack years of smoking and sputum atypia) treated with iloprost vs placebo. * Determine whether this drug modulates Ki-67 proliferation index (Antigen Ki-67) in these patients. * Determine whether this drug affects prostaglandin metabolism in these patients. * Determine the toxicity profile of this drug in these patients. Secondary * Determine whether this drug modulates a panel of biomarkers, including MCM-2(Minichromosome maintenance protein: forms DNA helicase), EGFR (Epidermal growth factor receptor: cell surface receptor for the epidermal growth factor family of proteins. Mutations in EGFR expression or activity can result in cancer.) , HER2/neu (Human epidermal growth factor receptor 2 HER2 is a member of the EGFR family), RARβ (Retinoic Acic Receptor Beta is a nuclear transcription regulator and a member of the thyroid-steroid hormone receptor superfamily), p53, FHIT (Fragile histidine triad protein is an enzyme involved in purine metabolism and had been demonstrated to be a tumor suppressor), apoptotic index, and microvessel density, in these patients. * Determine the genes whose expression is altered by this drug in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to smoking status (current vs former) and participating center. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral iloprost twice daily. * Arm II: Patients receive oral placebo twice daily. In both arms, treatment continues for 6 months in the absence of unacceptable toxicity. Patients are followed at 1 month and then annually thereafter. PROJECTED ACCRUAL: A total of 152 patients (76 \[38 current smokers and 38 former smokers\] per treatment arm) will be accrued for this study within 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Current or former smoker with ≥ 20 pack-year history of smoking with no tobacco use within the past 6 months
- •Mild atypia or worse on sputum cytology, or
- •Bronchial biopsy with mild or worse dysplasia within the past 12 months
- •Age 18 and over
- •SWOG (Southwest Oncology Group)0-2
- •Life expectancy at least 6 months
- •Granulocyte count \> 1,500/mm\^3
- •Platelet count \> 100,000/mm\^3
- •Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
- •Transaminases ≤ 2.5 times ULN
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I
Patients receive oral iloprost twice daily for 6 months in the absence of unacceptable toxicity.
Intervention: iloprost
Arm II
Patients receive oral placebo twice daily for 6 months in the absence of unacceptable toxicity.
Intervention: placebo
Outcomes
Primary Outcomes
Change in Average (Follow-up - Baseline) From All Biopsies
Time Frame: Nine years
This outcome measure is created for each subject as follows: From all biopsies scored at the baseline bronchoscopy, the mean WHO score is calculated. From all biopsies scored at the follow-up bronchoscopy, the mean WHO score is calculated.Histology on bronchial biopsies pre-treatment and post-treatment will be compared. All biopsies will be graded according to the WHO classification for bronchial epithelium for this outcome, and all the following outcomes. WHO Classification Grade Normal 1.0 Reserve Cell Hyperplasia 2.0 Metaplasia 3.0 Mild Dysplasia 4.0 Moderate Dysplasia 5.0 Severe Dysplasia 6.0 Carcinoma in Situ 7.0 Carcinoma 8.0 The difference (follow-up mean - baseline mean) is used as the outcome measure for each subject.
Secondary Outcomes
- Change in Maximum (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Average (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Maximum (Follow-up - Baseline) Using Matched Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using All Biopsies(9 Years)
- Change in Average (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Reference Sites(9 Years)
- Change in Maximum (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)
- Change in Average (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)
- Change in Dysplasia Index (Follow-up - Baseline) Using Baseline Non-Normal Pairs(9 Years)