Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00330382
First received: May 25, 2006
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

This randomized phase II trial is studying how well Bowman-Birk inhibitor concentrate works in preventing cancer in patients with oral leukoplakia. Chemoprevention is the use of certain substances to keep cancer from forming, growing, or coming back. The use of Bowman-Birk inhibitor concentrate, a substance made from soy, may keep cancer from forming in patients with oral leukoplakia


Condition Intervention Phase
Lip and Oral Cavity Cancer
Oral Leukoplakia
Oropharyngeal Cancer
Tongue Cancer
Drug: Bowman-Birk inhibitor concentrate
Other: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Comparison of proportion responding in treatment and placebo arms after six months on drug [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The primary analysis will be intent-to-treat (Theresa et al, 2000). Secondary analyses of proportion responders will be by logistic regression (e.g., Hosmer & Lemeshow, 1989) to relate probability of clinical response to models including treatment and other categorical or continuous variables, such as sex, age, use of tobacco and alcohol (should these show variability), dietary elements, and biomarkers. Models fitting these covariates to relative percent change in total lesion area, as a continuous measure, will be assessed via multiple-regression techniques (e.g., Zar, 1984).

  • Histologic response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be primarily analyzed as a categorical variable. Fisher's exact test will be used to determine if histologic response varies with treatment arm, in an intent-to-treat analysis. Secondary analyses of histologic response will parallel those described for clinical response: logistic regression will be used to fit models of categorical response to sets of covariates, and multiple-regression techniques will be used to fit models of covariates to histologic response as a continuous measure.


Secondary Outcome Measures:
  • Effects on intermediate marker endpoint levels [ Time Frame: Up to 3 months post-treatment ] [ Designated as safety issue: No ]
    Will accommodate the repeated-measures nature of the data, and be embodied by t-test within an arm, linear mixed modesl (Davis 2002).

  • Correlation of clinical and histologic response with cellular levels of proteolytic activity, erb-B2 (neu), retinioc acid receptor β, bcl-2, and mutant p53 expression, and serum levels of neu [ Time Frame: Up to 3 months post-treatment ] [ Designated as safety issue: No ]
    Will involve logistic or multiple regression and/or contingency-table analyses, as appropriate (Freeman, 1987).

  • Differential occurrence of side effects between arms [ Time Frame: Up to 3 months post-treatment ] [ Designated as safety issue: Yes ]
    Will be evaluated by contingency-table methods.


Enrollment: 210
Study Start Date: January 1999
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (Bowman-Birk inhibitor concentrate)
Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months
Drug: Bowman-Birk inhibitor concentrate
Given orally
Other Name: BBIC
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive oral placebo twice daily for 6 months
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine if chemoprevention by the Bowman-Birk inhibitor concentrate (BBIC) can prevent cancer in patients with oral leukoplakia (OL).

II. Determine the clinical and histologic response rate of OL to BBIC.

SECONDARY OBJECTIVES:

I. Measure the effect of BBIC on intermediate marker endpoint levels. II. Correlate the clinical and histologic responses of OL with cellular levels of proteolytic activity, erb-B2 (neu), retinioc acid receptor β, bcl-2, and mutant p53 expression, and serum levels of neu.

III. Determine the individual and group side effects of BBIC.

OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled, study. Prior to randomization, all patients receive oral placebo for 4 weeks. Patients who show good compliance (> 75% packet count) are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oral placebo twice daily for 6 months in the absence of disease progression or unacceptable toxicity.

Patients complete questionnaires about diet, tobacco, and alcohol usage at baseline and at the completion of study treatment. Blood, urine, and biopsy tissue are collected at baseline and at the completion of study treatment. Oral mucosal cells are collected at baseline, during the run-in phase, at randomization, after completion of study treatment, and at 3 months after completion of study treatment. Samples are examined for protease activity, levels of bcl-2 and erbB-2, mutant p53 oncogene expression and epidermal growth factor receptor, and retinoic acid receptor-β expression.

After completion of study treatment, patients are followed at 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically and clinically confirmed oral leukoplakia and/or erythroplakia
  • Bidimensionally measurable disease (≥ 100 mm^2 for total area of all lesions) after biopsy
  • No presence of obvious head and neck aerodigestive tract cancer, carcinoma in situ, or previously treated head and neck cancer within the past 2 years
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reaction to soybeans, sorbitol, sucrose, artificial flavorings, aspartame, saccharin, or lidocaine
  • At least 6 months since prior Bowman-Birk inhibitor concentrate
  • At least 6 months since prior participation in another randomized clinical trail
  • At least 3 months since prior systemic steroids or topical oral steroid preparations

    • Topical nasal steroid sprays or cutaneous preparations with minimal systemic absorption for nasal or dermatologic disorders allowed
  • More than 6 months since prior beta carotene capsules
  • At least 2 years since prior retinoid or other beta carotene therapy, including > 25,000 IU of vitamin A for any reason

    • Up to 2 multivitamins per day allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330382

Locations
United States, California
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
Sponsors and Collaborators
Investigators
Principal Investigator: Frank Meyskens University of California Medical Center At Irvine-Orange Campus
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00330382     History of Changes
Other Study ID Numbers: NCI-2009-00888, 98-34, U01CA072294
Study First Received: May 25, 2006
Last Updated: March 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukoplakia
Leukoplakia, Oral
Lip Neoplasms
Mouth Neoplasms
Oropharyngeal Neoplasms
Head and Neck Neoplasms
Lip Diseases
Mouth Diseases
Neoplasms
Neoplasms by Site
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Pathological Conditions, Anatomical
Pharyngeal Diseases
Pharyngeal Neoplasms
Precancerous Conditions
Stomatognathic Diseases

ClinicalTrials.gov processed this record on October 23, 2014