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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
British Columbia Cancer Agency
ClinicalTrials.gov Identifier:
NCT00522197
First received: August 28, 2007
Last updated: March 7, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Precancerous Condition
Dietary Supplement: multi-herbal agent ACAPHA
Dietary Supplement: Sugar Pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase II Trial of ACAPHA in Former Smokers With Intraepithelial Neoplasia

Resource links provided by NLM:


Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:
  • Efficacy and safety of multi-herbal agent ACAPHA as measured by combined histopathology and nuclear morphometry of intraepithelial neoplasia lesions [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in the severity of dysplasia by bronchial biopsy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in the morphometric index of sputum cells, bronchial biopsies, and epithelial cells in the bronchoalveolar lavage fluid (BAL) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • MIB-1, bcl-2, and TUNEL immunostaining in the bronchial biopsies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Methylation biomarkers in the sputa, oral brush, and BAL cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Gene expression analysis of RNA from bronchial brush cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Volumetric measurement of CT scan-detected lung nodules before and after treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 90
Study Start Date: September 2002
Study Completion Date: November 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ACAPHA Dietary Supplement: multi-herbal agent ACAPHA
Placebo Comparator: Sugar Pill 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.

  Eligibility

Ages Eligible for Study:   45 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00522197

Sponsors and Collaborators
British Columbia Cancer Agency
Investigators
Principal Investigator: Stephen Lam, MD British Columbia Cancer Agency
  More Information

Additional Information:
No publications provided

Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT00522197     History of Changes
Other Study ID Numbers: CDR0000562055, U01CA096109, BCCA-H02-61177-A002, BCCA-R02-1177
Study First Received: August 28, 2007
Last Updated: March 7, 2012
Health Authority: United States: Federal Government

Keywords provided by British Columbia Cancer Agency:
non-small cell lung cancer
small cell lung cancer
squamous lung dysplasia

Additional relevant MeSH terms:
Neoplasms
Lung Neoplasms
Precancerous Conditions
Carcinoma in Situ
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on April 15, 2014