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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial

Conditions
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Lip and Oral Cavity Cancer, Oral Leukoplakia, Oropharyngeal Cancer, Tongue Cancer

Intervention / Treatment
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* Drug: Bowman-Birk inhibitor concentrate
* Other: placebo
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (Bowman-Birk inhibitor concentrate)<br>Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months | Drug: Bowman-Birk inhibitor concentrate<br>* Given orally<br>* Other names: BBIC;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive oral placebo twice daily for 6 months | Other: placebo<br>* Given orally<br>* Other names: PLCB;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Percent Change in Total Lesion Area After 6 Months on Study | Relative percent change in total lesion area was defined as 100 times (area posttreatment minus area pretreatment) all divided by pretreatment area. | 6 months | 
| Number of Participants by Category of Clinical Response at 6 Months | Category of clinical response was based on the magnitude of relative percent change in total lesion area. A complete response (CR) was declared if the relative percent change in total lesion area was minus 100 percent. A partial response (PR) was a relative percent decrease in total lesion area of 50% or more, without being a CR. Disease progression was a relative percent increase in total lesion area of at least 50%. Remaining cases were declared to be stable disease. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen | The reviewer was blinded to study-arm assignment (drug or placebo), but not to time point of specimen. For each specimen, the reviewer marked a continuum to indicate degree of tissue abnormality. The continuum was 140 mm long, and anchored by the word 'Normal' on the left and 'Malignant' on the right. The distance from the left edge of the continuum to the reviewer's mark, in mm, was determined. For analyses, a score was formed by subtracting the pretreatment value from the 6-month value. Thus, a retreat from 'Malignancy' over time produces a negative score, a score of zero denotes no change, and a positive score denotes a worsening situation. Positive values indicate histologic worsening, whereas negative scores denote improvement over the 6-month study period. | Baselie to 6 months | 
| Clinical Impression From Photographs | A secondary clinical response measure was bsaed on blinded, comparative judgments of pairs of photographs of the same lesion at baseline and 6 months on study. Picture pairs were assigned to album page, one pair per page, at random. Five physicians experienced with evaluation of oral mucosal tissue abnormalities, but blinded to study arm and time point, independently compared the pictures in each pair using a 7-point scale. The scale ranged from, top photo shows a complete response relative to the bottom photo, through, the same degree of disease is shown by top photo and bottom photo, to bottom photo shows a complete response relative to the top photo. Raw scores were transformed to account for relative position of the earlier and later photo, and averaged across the 5 reviewers. Final scores ranged from one, denoting a CR at 6 months, to 4, which indicated no change, through 7, which indicated that the 6-month photo depicted a much worse situation than the pretreatment photo. | Baseline to 6 months | 
| Relative Percent Change in Buccal-Cell Neu Protein (ng/mg) | 100% x (Posttreatment value - pretreatment value)/(pretreatment value) | Baseline to 6 months | 
| Relative Percent Change in Serum Neu Protein (ng/ml) | 100% x (Posttreatment value - pretreatment value)/(pretreatment value) | Baseline to 6 months | 
| Relative Percent Change in Protease Activity (Delta RFU/Min/µg) | 100% x (Posttreatment value - pretreatment value)/(pretreatment value) | Baseline to 6 months | 
| Number of Participants Report at Least 1 Adverse Event During the Study | The onset of adverse event is between the randomizaiton date and off-study date | Randomized date to Off-study date, up to 21 months | 
| Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months |  | Baseline to 6 months |