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.

Condition	Treatment or Intervention	Phase
Non-small cell lung cancer Small Cell Lung Cancer Drug Toxicity	Drug: isotretinoin  Drug: vitamin E  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: chemoprotection  Procedure: supportive care/therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Colorado
      Lung Cancer Institute, Denver,  Colorado,  80218,  United States
      National Jewish Center for Immunology and Respiratory Medicine, Denver,  Colorado,  80206,  United States
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Denver,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States

Study chairs or principal investigators

Karen Kelly, MD,  Study Chair,  University of Colorado Cancer Center   

Study ID Numbers:  CDR0000063730; UCHSC-92382; NCI-V94-0506
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002586
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08