A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
18 Years
N/A
Both
Lung Cancer, Precancerous Condition
Trial Information
A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
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 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Current or former* smoker with ≥ 20 pack-year history of smoking NOTE: *Defined as 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
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- SWOG (Southwest Oncology Group)0-2
Life expectancy
- At least 6 months
Hematopoietic
- Granulocyte count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- No clinically apparent bleeding diathesis
Hepatic
- Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
- Transaminases ≤ 2.5 times ULN
- Bilirubin ≤ 2.0 mg/dL
- Albumin ≥ 2.5 g/dL
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- No clinically active coronary artery disease
- No myocardial infarction within the past 6 weeks
- No chest pain
- No congestive heart failure
- No cardiac dysrhythmia that is potentially life-threatening
- Well-controlled atrial fibrillation OR rare (< 2 minutes) premature ventricular
contractions allowed
- No ventricular tachycardia
- No multifocal premature ventricular contractions or supraventricular tachycardias
with rapid ventricular response
Pulmonary
- No pneumonia or acute bronchitis within the past 2 weeks
- No hypoxemia (< 90% saturation with supplemental oxygen)
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Able and willing to undergo bronchoscopy
- No malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No serious medical condition that would preclude bronchoscopy or study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- More than 5 years since prior chemotherapy
Endocrine therapy
- More than 6 weeks since prior inhaled steroids
Radiotherapy
- More than 5 years since prior thoracic radiotherapy
Surgery
- Not specified
Other
- No prior prostacyclin
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Outcome Measure:
Change in Average (Follow-up - Baseline) From All Biopsies
Outcome Description:
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.
Outcome Time Frame:
Nine years
Safety Issue:
No
Principal Investigator
Robert Keith, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Colorado, Denver
Authority:
United States: Federal Government
Study ID:
01-0279
NCT ID:
NCT00084409
Start Date:
November 2001
Completion Date:
January 2009
Related Keywords:
- Lung Cancer
- Precancerous Condition
- non-small cell lung cancer
- squamous lung dysplasia
- Lung Neoplasms
- Precancerous Conditions
Name | Location |
|---|---|
| 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 |
