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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00330382
First received: May 25, 2006
Last updated: December 16, 2014
Last verified: February 2014
  Purpose
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

Condition Intervention Phase
Lip and Oral Cavity Cancer
Oral Leukoplakia
Oropharyngeal Cancer
Tongue Cancer
Drug: Bowman-Birk inhibitor concentrate
Other: placebo
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 325
Study Start Date: January 1999
Study Completion Date: May 2013
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (Bowman-Birk inhibitor concentrate)
Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months
Drug: Bowman-Birk inhibitor concentrate
Given orally
Other Name: BBIC
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive oral placebo twice daily for 6 months
Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00330382

Locations
United States, California
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Frank Meyskens University of California Medical Center At Irvine-Orange Campus
  More Information

Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00330382     History of Changes
Other Study ID Numbers: NCI-2009-00888  98-34  U01CA072294 
Study First Received: May 25, 2006
Results First Received: October 3, 2014
Last Updated: December 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Mouth Neoplasms
Lip Neoplasms
Tongue Neoplasms
Leukoplakia
Leukoplakia, Oral
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Mouth Diseases
Lip Diseases
Tongue Diseases
Precancerous Conditions
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on July 28, 2016