Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
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.
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention
Comparison of proportion responding in treatment and placebo arms after six months on drug
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).
University of California Medical Center At Irvine-Orange Campus
United States: Food and Drug Administration
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