Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Iloprost in Preventing Lung Cancer in Patients at High Risk for This Disease

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Prevention	Active	18 and over	NCI	UCHSC-01279 NCT00084409

Special Category: SPORE trial

Objectives

Primary

1. 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.
2. Determine whether this drug modulates Ki-67 proliferation index in these patients.
3. Determine whether this drug affects prostaglandin metabolism in these patients.
4. Determine the toxicity profile of this drug in these patients.

Secondary

1. Determine whether this drug modulates a panel of biomarkers, including MCM-2, EGFR, HER2/neu, RARβ, p53, FHIT, apoptotic index, and microvessel density, in these patients.
2. Determine the genes whose expression is altered by this drug in these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• SWOG 0-2

Life expectancy

• At least 6 months

Hematopoietic

• Granulocyte count > 1,500/mm³
• Platelet count > 100,000/mm³
• 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

Expected Enrollment

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.

Outcomes

Measures of improvement in histologic response at baseline and 6 months after completion of treatment
Change in mean, dysplastic index, and worst histologic score

Change in the proliferative intermediate marker Ki-67

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.

Trial Contact Information

Trial Lead Organizations

University of Colorado Cancer Center at UC Health Sciences Center

Robert Keith, MD, Principal investigator		Ph: 303-393-2869; 800-473-2288

U.S.A.
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Denver
	Veterans Affairs Medical Center - Denver
		Robert Keith, MD	Ph:  303-393-2869 888-336-8262
Maryland
	Baltimore
	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
		Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Center at John Hopkins	Ph:  410-955-8804
			Email: jhcccro@jhmi.edu
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Pennsylvania
	Pittsburgh
	UPMC Cancer Centers
		Clinical Trials Office - UPMC Cancer Centers	Ph:  412-647-8073
Tennessee
	Nashville
	Vanderbilt-Ingram Cancer Center
		Clinical Trials Office - Vanderbilt-Ingram Cancer Center	Ph:  1-800-811-8480;

Registry Information
Official Title		A Randomized Phase II Chemoprevention Study of Iloprost Versus Placebo in Patients at High Risk for Lung Cancer
Trial Start Date		2001-11-01
Registered in ClinicalTrials.gov		NCT00084409
Date Submitted to PDQ		2003-10-20
Information Last Verified		2008-04-06
NCI Grant/Contract Number		CA46934, CA58187