Clinical trial NCT00330382: Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
Official title: Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lip and Oral Cavity Cancer
Oral Leukoplakia
Oropharyngeal Cancer
Tongue Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-05-26
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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 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

Primary outcomes:
measure: Relative Percent Change in Total Lesion Area After 6 Months on Study
timeFrame: 6 months
measure: Number of Participants by Category of Clinical Response at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen
timeFrame: Baselie to 6 months
measure: Clinical Impression From Photographs
timeFrame: Baseline to 6 months
measure: Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)
timeFrame: Baseline to 6 months
measure: Relative Percent Change in Serum Neu Protein (ng/ml)
timeFrame: Baseline to 6 months
measure: Relative Percent Change in Protease Activity (Delta RFU/Min/µg)
timeFrame: Baseline to 6 months
measure: Number of Participants Report at Least 1 Adverse Event During the Study
timeFrame: Randomized date to Off-study date, up to 21 months
measure: Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
timeFrame: Baseline to 6 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Medical Center At Irvine-Orange Campus
state: California
Study officials:
affiliation: University of California Medical Center At Irvine-Orange Campus
name: Frank Meyskens
role: PRINCIPAL_INVESTIGATOR
References:
citation: Meyskens FL. Development of Bowman-Birk inhibitor for chemoprevention of oral head and neck cancer. Ann N Y Acad Sci. 2001 Dec;952:116-23. doi: 10.1111/j.1749-6632.2001.tb02732.x.
citation: Meyskens FL Jr. Development of difluoromethyl-ornithine and Bowman-Birk inhibitor as chemopreventive agents by assessment of relevant biomarker modulation: some lessons learned. IARC Sci Publ. 2001;154:49-55.
citation: Armstrong WB, Taylor TH, Kennedy AR, Melrose RJ, Messadi DV, Gu M, Le AD, Perloff M, Civantos F, Goodwin WJ, Wirth LJ, Kerr AR, Meyskens FL Jr. Bowman birk inhibitor concentrate and oral leukoplakia: a randomized phase IIb trial. Cancer Prev Res (Phila). 2013 May;6(5):410-8. doi: 10.1158/1940-6207.CAPR-13-0004.
citation: Armstrong WB, Wan XS, Kennedy AR, Taylor TH, Meyskens FL Jr. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope. 2003 Oct;113(10):1687-702. doi: 10.1097/00005537-200310000-00007.