A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
- 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 in these patients.
- Determine whether this drug affects prostaglandin metabolism in these patients.
- Determine the toxicity profile of this drug in these patients.
- 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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Change in Average (Follow-up - Baseline) From All Biopsies
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.
Robert Keith, MD
University of Colorado, Denver
United States: Federal Government
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|
|Vanderbilt-Ingram Cancer Center||Nashville, Tennessee 37232-6838|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Veterans Affairs Medical Center - Denver||Denver, Colorado 80220|
|UPMC Cancer Centers||Pittsburgh, Pennsylvania 15232|
|University of Colorado Cancer Center at UC Health Sciences Center||Aurora, Colorado 80045|