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

British Columbia Cancer Agency

Status and phase

Completed

Phase 2

Conditions

Precancerous Condition

Lung Cancer

Treatments

Dietary Supplement: Sugar Pill

Dietary Supplement: multi-herbal agent ACAPHA

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00522197

BCCA-H02-61177-A002

U01CA096109 (U.S. NIH Grant/Contract)

BCCA-R02-1177

CDR0000562055

Details and patient eligibility

About

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.

Full 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.

Enrollment

90 patients

Sex

All

Ages

45 to 74 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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