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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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 comp
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Relative Percent Change in Total Lesion Area After 6 Months on Study [ Time Frame: 6 months ]
  Relative percent change in total lesion area was defined as 100 times (area posttreatment minus area pretreatment) all divided by pretreatment area.
• Number of Participants by Category of Clinical Response at 6 Months [ Time Frame: 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.

Original Primary Outcome:

Current Secondary Outcome:

• The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen [ Time Frame: Baselie to 6 months ]
  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.
• Clinical Impression From Photographs [ Time Frame: Baseline to 6 months ]
  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.
• Relative Percent Change in Buccal-Cell Neu Protein (ng/mg) [ Time Frame: Baseline to 6 months ]
  100% x (Posttreatment value - pretreatment value)/(pretreatment value)
• Relative Percent Change in Serum Neu Protein (ng/ml) [ Time Frame: Baseline to 6 months ]
  100% x (Posttreatment value - pretreatment value)/(pretreatment value)
• Relative Percent Change in Protease Activity (Delta RFU/Min/µg) [ Time Frame: Baseline to 6 months ]
  100% x (Posttreatment value - pretreatment value)/(pretreatment value)
• Number of Participants Report at Least 1 Adverse Event During the Study [ Time Frame: Randomized date to Off-study date, up to 21 months ]
  The onset of adverse event is between the randomizaiton date and off-study date
• Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months [ Time Frame: Baseline to 6 months ]

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 25, 2006
Date Started: January 1999
Date Completion:
Last Updated: December 16, 2014
Last Verified: February 2014