Lung Cancer, Precancerous Condition
Conditions
Keywords
non-small cell lung cancer, small cell lung cancer, squamous lung dysplasia
Brief summary
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of ACAPHA, a combination of six herbs, may prevent lung cancer from forming in former smokers with bronchial intraepithelial neoplasia. PURPOSE: This randomized phase II trial is studying the side effects and how well ACAPHA works in preventing lung cancer in former smokers with bronchial intraepithelial neoplasia.
Detailed description
OBJECTIVES: * Determine the efficacy and safety of multi-herbal agent ACAPHA in former smokers with bronchial intraepithelial neoplasia. * Evaluate whether ACAPHA can modulate other surrogate endpoint biomarkers of aberrant methylation, cell cycle regulation, apoptosis, as well as phase I and II enzyme regulation. * Establish a library of in vivo confocal microendoscopy images with corresponding histopathology, nuclear morphometry, and other biomarker information to assess the potential of confocal microendoscopy as a nonbiopsy method in assessing the effect of chemoprevention agents. OUTLINE: Patients are stratified according to gender. Patients are randomized to 1 of 2 arms. * Arm I: Patients receive oral multi-herbal agent ACAPHA twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of ACAPHA. * Arm II: Patients receive oral placebo twice daily for 6 months. Patients achieving a partial response receive an additional 6 months of placebo. Patients with progressive disease receive ACAPHA twice daily for 6 months. Patients undergo sputum cytology, oral and bronchial brushings, bronchoalveolar lavage, and bronchial tissue biopsies at baseline and at 6 and 12 months. Samples are analyzed for histopathological and morphometric cell changes; MIB-1 bcl-2, and TUNEL immunostaining; methylation biomarkers; and gene expression analysis of RNA. After completion of study therapy, patients are followed at 1 and 6 months.
Interventions
DIETARY_SUPPLEMENTmulti-herbal agent ACAPHA
DIETARY_SUPPLEMENTSugar Pill
Sponsors
National Cancer Institute (NCI)
British Columbia Cancer Agency
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * One or more areas of bronchial intraepithelial neoplasia (IEN) (metaplasia/dysplasia) with a nuclear morphometry index \> 1.36 and a surface diameter \> 1.2 mm on autofluorescence bronchoscopy * Atypical sputum cells as determined by computer-assisted image analysis * Former smoker (i.e., stopped smoking at least 1 year ago) who has smoked at least 30 pack-years (i.e., 1 pack/day for 30 years or more) * Exhaled carbon monoxide level \< 5 ppm * No invasive cancer on bronchoscopy or abnormal spiral chest CT scan suspicious of lung cancer PATIENT CHARACTERISTICS: * ECOG performance status 0 or 1 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Normal renal function tests (BUN, creatinine, urinalysis) * Normal liver function tests (AST, ALT, bilirubin, alkaline phosphatase) * No chronic active hepatitis or liver cirrhosis * No acute bronchitis or pneumonia within the past month * No known reaction to xylocaine * No medical condition that, in the opinion of the investigator, could jeopardize the patient's safety during participation in the study, including any of the following: * Acute or chronic respiratory failure * Unstable angina * Uncontrolled congestive heart failure * Bleeding disorder PRIOR CONCURRENT THERAPY: * Not specified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL) | 12 months |
| MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies | 12 months |
| Changes in the severity of dysplasia by bronchial biopsy | 6 months |
| Gene expression analysis of RNA from bronchial brush cells | 12 months |
| Volumetric measurement of CT scan-detected lung nodules before and after treatment | 12 months |
| Methylation biomarkers in the sputa, oral brush, and BAL cells | 12 months |
Outcome results
None listed