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

Phase 2

Completed

• Conditions: Lung Cancer; Precancerous Condition
• Interventions: Dietary Supplement: multi-herbal agent ACAPHA; Dietary Supplement: Sugar Pill

• Registration Number: NCT00522197
• Lead Sponsor: British Columbia Cancer Agency

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.

Study Timeline

• Study Start: 2002-09
• Study First Submitted: 2007-08-28
• Study First Submitted QC: 2007-08-28
• Study First Posted: 2007-08-29
• Primary Completion: 2008-10
• Study Completion: 2008-11
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-07
• Last Update Posted: 2012-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
ACAPHA	multi-herbal agent ACAPHA	-
Sugar Pill	Sugar Pill	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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