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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer; Precancerous Condition
• Intervention / Treatment: Dietary supplement: multi-herbal agent ACAPHA; Dietary supplement: Sugar Pill

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Sugar Pill	Dietary supplement: Sugar Pill
Active Comparator: ACAPHA	Dietary supplement: multi-herbal agent ACAPHA

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: British Columbia Cancer Agency
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Stephen Lam, MD, British Columbia Cancer Agency

Study record dates

Study Major Dates

• Study Start: September 1, 2002
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: August 28, 2007
• First Submitted That Met QC Criteria: August 28, 2007
• First Posted (Estimate): August 29, 2007

Study Record Updates

• Last Update Posted (Estimate): March 9, 2012
• Last Update Submitted That Met QC Criteria: March 7, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: non-small cell lung cancer; small cell lung cancer; squamous lung dysplasia
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Precancerous Conditions
• Other Study ID Numbers: CDR0000562055; U01CA096109 (U.S. NIH Grant/Contract); BCCA-H02-61177-A002; BCCA-R02-1177