ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial Intraepithelial Neoplasia

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia

Conditions
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Lung Cancer, Precancerous Condition

Intervention / Treatment
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* Dietary Supplement: multi-herbal agent ACAPHA
* Dietary Supplement: Sugar Pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ACAPHA<br> | Dietary Supplement: multi-herbal agent ACAPHA<br> <br> |
| Placebo Comparator: Sugar Pill<br> | Dietary Supplement: Sugar Pill<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the severity of dysplasia by bronchial biopsy |  | 6 months | 
| 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 | 
| Methylation biomarkers in the sputa, oral brush, and BAL cells |  | 12 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-small cell lung cancer, small cell lung cancer, squamous lung dysplasia