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

British Columbia Cancer Agency90 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

Lung Cancer Precancerous Condition

Interventions

multi-herbal agent ACAPHADIETARY_SUPPLEMENT

Sugar PillDIETARY_SUPPLEMENT

Eligibility

Sex: ALLMin age: 45 YearsMax age: 74 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions

Time frame: 12 months

Secondary Outcomes

Changes in the severity of dysplasia by bronchial biopsy

Time frame: 6 months

Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL)

Time frame: 12 months

MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies

Time frame: 12 months

Methylation biomarkers in the sputa, oral brush, and BAL cells

Time frame: 12 months

Gene expression analysis of RNA from bronchial brush cells

Time frame: 12 months

Volumetric measurement of CT scan-detected lung nodules before and after treatment

Time frame: 12 months

Data from ClinicalTrials.gov

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