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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00522197
• Other study ID #: CDR0000562055
• Secondary ID: U01CA096109BCCA-
• Status: Completed
• Phase: Phase 2
• First received: August 28, 2007
• Last updated: March 7, 2012
• Start date: September 2002
• Est. completion date: November 2008

Study information

• Verified date: March 2012
• Source: British Columbia Cancer Agency
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: November 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 74 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma in Situ
• Lung Cancer
• Lung Neoplasms
• Precancerous Condition
• Precancerous Conditions

Intervention

Dietary Supplement:
• multi-herbal agent ACAPHA

• Sugar Pill

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions		12 months	Yes
Secondary	Changes in the severity of dysplasia by bronchial biopsy		6 months	No
Secondary	Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL)		12 months	No
Secondary	MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies		12 months	No
Secondary	Methylation biomarkers in the sputa, oral brush, and BAL cells		12 months	No
Secondary	Gene expression analysis of RNA from bronchial brush cells		12 months	No
Secondary	Volumetric measurement of CT scan-detected lung nodules before and after treatment		12 months	No