Official Title: “ASSESSMENT OF INTERMEDIATE ENDPOINT BIOMARKERS TO 13-CIS RETINOIC ACID WITH OR WITHOUT ALPHA TOCOPHEROL OR OBSERVATION”

RATIONALE: Isotretinoin may prevent the development of cancer cells.

PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of isotretinoin with or without vitamin E for chemoprevention of cancer in persons at high risk of developing lung cancer.

Study Type: Interventional

Study Design: Prevention, Randomized, Double-Blind, Active Control

OBJECTIVES: - Determine whether any intermediate endpoint biomarkers in patients at high risk for the development of lung cancer change after treatment with isotretinoin given with or without vitamin E. - Determine whether vitamin E can reduce the toxic effects of low-dose isotretinoin administered for 1 year in these patients.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to smoking status (smoker vs ex-smoker).

All patients undergo bronchoscopy. All observed lesions are biopsied. Patients are then randomized to one of three treatment arms. - Arm I: Patients receive oral isotretinoin daily. - Arm II: Patients receive oral isotretinoin and oral vitamin E daily. - Arm III: Patients undergo observation only. Treatment continues in arms I and II for 1 year in the absence of unacceptable toxicity.

Patients are followed annually for 2 years.

PROJECTED ACCRUAL: A total of 60 patients (20 per arm) will be accrued for this study within 3 years.

Intervention(s) in this Clinical Trial

• Drug: isotretinoin
• Drug: vitamin E

DISEASE CHARACTERISTICS:

• Current smokers with at least a 40-pack/year history OR
• Former smokers considered at high risk for the development of lung cancer
• At least a 40-pack/year history
• No smoking in the past 12 months
• At least 1 of the following high-risk conditions:
• Mild, moderate, or severe dysplasia
• Carcinoma in situ
• Surgically cured head and neck cancer with at least mild atypia on staging bronchoscopy (includes carcinoma in situ)
• No pneumonia or acute bronchitis requiring antibiotics within past 2 months prior to entry
• No evidence of tumor on chest x-ray

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count greater than 1,500/mm^3
• Platelet count greater than 200,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• ALT less than 4 times upper limit of normal
• No hypercholesterolemia/hypertriglyceridemia

Renal:

• Creatinine less than 1.5 mg/dL

Cardiovascular:

• No active atherosclerotic cardiovascular disease (angina, claudication)

Other:

• No other malignancy within past 5 years except surgically cured skin cancer or in situ cancer
• No insulin-dependent diabetes mellitus
• No history of abnormal bleeding
• No other serious concurrent illness
• No fertile women

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• Not specified
• Chemotherapy
• Not specified
• Endocrine therapy
• Not specified
• Radiotherapy
• Not specified
• Surgery
• See Disease Characteristics
• Other
• See Disease Characteristics
• No concurrent tetracycline or minocycline
• No concurrent vitamin supplements

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Colorado at Denver and Health Sciences Center

Overall Clinical Trial Officials and Contacts

Karen Kelly, MD Study Chair University of Colorado at Denver and Health Sciences Center  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002586

Study ID Number: CDR0000063730

ClinicalTrials.gov Identifier: NCT00002586

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database