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

Phase 2
45 Years
74 Years
Not Enrolling
Lung Cancer, Precancerous Condition

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Trial Information

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


- 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

- 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

- 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


- 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


- 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


- Not specified

Type of Study:


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:


Principal Investigator

Stephen Lam, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

British Columbia Cancer Agency


United States: Federal Government

Study ID:




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