Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
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
Lip and Oral Cavity Cancer
Drug: Bowman-Birk inhibitor concentrate
Other: laboratory biomarker analysis
|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|
- 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.
- 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.
|Study Start Date:||January 1999|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Arm I (Bowman-Birk inhibitor concentrate)
Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months
Drug: Bowman-Birk inhibitor concentrate
Other Name: BBICOther: laboratory biomarker analysis
Placebo Comparator: Arm II (placebo)
Patients receive oral placebo twice daily for 6 months
Other Name: PLCBOther: laboratory biomarker analysis
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.
|United States, California|
|University of California Medical Center At Irvine-Orange Campus|
|Orange, California, United States, 92868|
|Principal Investigator:||Frank Meyskens||University of California Medical Center At Irvine-Orange Campus|