Clinical trial NCT00522197: ACAPHA in Preventing Lung Cancer in Former Smokers With Bronchial Intraepithelial Neoplasia
Official title: A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Precancerous Condition
Keywords: non-small cell lung cancer
small cell lung cancer
squamous lung dysplasia
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-08-29
Enrollment: 90
Sex: ALL
Minimum age (years): 45
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility 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

Primary outcomes:
measure: Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions
timeFrame: 12 months
Secondary outcomes:
measure: Changes in the severity of dysplasia by bronchial biopsy
timeFrame: 6 months
measure: Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL)
timeFrame: 12 months
measure: MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies
timeFrame: 12 months
measure: Methylation biomarkers in the sputa, oral brush, and BAL cells
timeFrame: 12 months
measure: Gene expression analysis of RNA from bronchial brush cells
timeFrame: 12 months
measure: Volumetric measurement of CT scan-detected lung nodules before and after treatment
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: British Columbia Cancer Agency
name: Stephen Lam, MD
role: PRINCIPAL_INVESTIGATOR
References: