Clinical trial NCT00084409: Iloprost in Preventing Lung Cancer in Patients at High Risk for This Disease
Official title: A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Precancerous Condition
Keywords: non-small cell lung cancer
squamous lung dysplasia
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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
* Bilirubin ≤ 2.0 mg/dL
* Albumin ≥ 2.5 g/dL
* Creatinine ≤ 1.5 mg/dL
* Well-controlled atrial fibrillation OR rare (\< 2 minutes) premature ventricular contractions allowed
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able and willing to undergo bronchoscopy

Exclusion Criteria

* Clinically apparent bleeding diathesis
* Ventricular tachycardia
* Multifocal premature ventricular contractions or supraventricular tachycardias with rapid ventricular response
* Pneumonia or acute bronchitis within the past 2 weeks
* Hypoxemia (\< 90% saturation with supplemental oxygen)
* Pregnant or nursing
* Malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* Serious medical condition that would preclude bronchoscopy or study participation
* Clinically active coronary artery disease
* Myocardial infarction within the past 6 weeks
* Chest pain
* Congestive heart failure
* Cardiac dysrhythmia that is potentially life-threatening

Exclusion for PRIOR CONCURRENT THERAPY:

* Biologic therapy (Not specified)
* More than 5 years since prior chemotherapy
* More than 6 weeks since prior inhaled steroids
* More than 5 years since prior thoracic radiotherapy
* Surgery (Not specified)
* No prior prostacyclin

Primary outcomes:
measure: Change in Average (Follow-up - Baseline) From All Biopsies
timeFrame: Nine years
Secondary outcomes:
measure: Change in Dysplasia Index (Follow-up - Baseline) Using All Biopsies
timeFrame: 9 Years
measure: Change in Average (Follow-up - Baseline) Using Reference Sites
timeFrame: 9 Years
measure: Change in Maximum (Follow-up - Baseline) Using Reference Sites
timeFrame: 9 Years
measure: Change in Dysplasia Index (Follow-up - Baseline) Using Reference Sites
timeFrame: 9 Years
measure: Change in Average (Follow-up - Baseline) Using Matched Sites
timeFrame: 9 Years
measure: Change in Maximum (Follow-up - Baseline) Using Matched Sites
timeFrame: 9 Years
measure: Change in Dysplasia Index (Follow-up - Baseline) Using Matched Sites
timeFrame: 9 Years
measure: Change in Average (Follow-up - Baseline) Using Baseline Non-Normal Pairs
timeFrame: 9 Years
measure: Change in Maximum (Follow-up - Baseline) Using Baseline Non-Normal Pairs
timeFrame: 9 Years
measure: Change in Dysplasia Index (Follow-up - Baseline) Using Baseline Non-Normal Pairs
timeFrame: 9 Years
Other outcomes:
measure: To Determine if Iloprost Can Modulate K-67 Proliferation Index in Patients at High Risk to Develop Lung Cancer
timeFrame: nine years
measure: To Determine Whether Iloprost Affects Prostaglandin Metabolism by Examining 4 Markers, PGIS, COX-2, PPAR and PPAR.
timeFrame: Nine years
measure: To Determine the Toxicity Profile of Iloprost in Patients at High Risk to Develop Lung Cancer.
timeFrame: Nine Years
measure: Define the Genes Whose Expression is Altered by Iloprost Treatment by Gene Expression Arrays and Quantitative PCR.
timeFrame: Nine Years
measure: To Determine Whether Iloprost Can Modulate a Panel of Biomarkes.
timeFrame: 9 years
Locations:
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: University of Colorado, Denver
name: Robert Keith, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Keith RL, Blatchford PJ, Kittelson J, Minna JD, Kelly K, Massion PP, Franklin WA, Mao J, Wilson DO, Merrick DT, Hirsch FR, Kennedy TC, Bunn PA Jr, Geraci MW, Miller YE. Oral iloprost improves endobronchial dysplasia in former smokers. Cancer Prev Res (Phila). 2011 Jun;4(6):793-802. doi: 10.1158/1940-6207.CAPR-11-0057.