A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia
45 Years
74 Years
Both
Lung Cancer, Precancerous Condition
Trial Information
A Phase II Trial of ACAPHA in Former Smokers With 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.
Inclusion 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
PRIOR CONCURRENT THERAPY:
- Not specified
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Outcome Measure:
Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
Outcome Time Frame:
12 months
Safety Issue:
Yes
Principal Investigator
Stephen Lam, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
British Columbia Cancer Agency
Authority:
United States: Federal Government
Study ID:
CDR0000562055
NCT ID:
NCT00522197
Start Date:
September 2002
Completion Date:
November 2008
Related Keywords:
- Lung Cancer
- Precancerous Condition
- non-small cell lung cancer
- small cell lung cancer
- squamous lung dysplasia
- Neoplasms
- Lung Neoplasms
- Precancerous Conditions
- Carcinoma in Situ
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