Bowman-Birk Inhibitor Concentrate in Preventing Cancer 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|
- Relative Percent Change in Total Lesion Area After 6 Months on Study [ Time Frame: 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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.
- The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen [ Time Frame: Baselie to 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]100% x (Posttreatment value - pretreatment value)/(pretreatment value)
- Relative Percent Change in Serum Neu Protein (ng/ml) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]100% x (Posttreatment value - pretreatment value)/(pretreatment value)
- Relative Percent Change in Protease Activity (Delta RFU/Min/µg) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]
|Study Start Date:||January 1999|
|Study Completion Date:||May 2013|
|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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00330382
|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|