ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00330382
Recruitment Status : Completed
First Posted : May 26, 2006
Results First Posted : December 19, 2014
Last Update Posted : December 19, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions: Lip and Oral Cavity Cancer
Oral Leukoplakia
Oropharyngeal Cancer
Tongue Cancer
Interventions: Drug: Bowman-Birk inhibitor concentrate
Other: placebo
Other: laboratory biomarker analysis

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 513 people were screened for participation across all 8 performance sites, of which 188 (37%) were ineligible and 325 were consented.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 325 consented, 157 (48%) completed the run-in period but 25 declined to continue, resulting in 132 randomized patients.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Participant Flow:   Overall Study
    Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo)
STARTED   67   65 
COMPLETED   43   48 
NOT COMPLETED   24   17 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies

Total Total of all reporting groups

Baseline Measures
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo)   Total 
Overall Participants Analyzed 
[Units: Participants]
 67   65   132 
Age 
[Units: Years]
Mean (Standard Deviation)
 58.25  (13.63)   60.64  (12.01)   59.42  (12.87) 
Gender 
[Units: Participants]
     
Female   26   25   51 
Male   41   40   81 


  Outcome Measures

1.  Primary:   Relative Percent Change in Total Lesion Area After 6 Months on Study   [ Time Frame: 6 months ]

Measure Type Primary
Measure Title Relative Percent Change in Total Lesion Area After 6 Months on Study
Measure Description Relative percent change in total lesion area was defined as 100 times (area posttreatment minus area pretreatment) all divided by pretreatment area.
Time Frame 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   43   46 
Relative Percent Change in Total Lesion Area After 6 Months on Study 
[Units: Percentage change]
Mean (Standard Deviation)
 -20.6  (52.4)   -17.1  (66.4) 

No statistical analysis provided for Relative Percent Change in Total Lesion Area After 6 Months on Study



2.  Primary:   Number of Participants by Category of Clinical Response at 6 Months   [ Time Frame: 6 months ]

Measure Type Primary
Measure Title Number of Participants by Category of Clinical Response at 6 Months
Measure Description 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.
Time Frame 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   43   46 
Number of Participants by Category of Clinical Response at 6 Months 
[Units: Participants]
   
Complete response (CR)   2   2 
Partial response (PR)   10   12 
Stable disease   27   26 
Disease progression   4   6 

No statistical analysis provided for Number of Participants by Category of Clinical Response at 6 Months



3.  Secondary:   The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen   [ Time Frame: Baselie to 6 months ]

Measure Type Secondary
Measure Title The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen
Measure Description 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.
Time Frame Baselie to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   41   47 
The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen 
[Units: Score]
Mean (Standard Deviation)
 1.2  (23.7)   3.6  (15.4) 

No statistical analysis provided for The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen



4.  Secondary:   Clinical Impression From Photographs   [ Time Frame: Baseline to 6 months ]

Measure Type Secondary
Measure Title Clinical Impression From Photographs
Measure Description 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.
Time Frame Baseline to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   45   46 
Clinical Impression From Photographs 
[Units: Score]
Mean (Standard Deviation)
 4.0  (1.0)   3.6  (0.9) 

No statistical analysis provided for Clinical Impression From Photographs



5.  Secondary:   Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)   [ Time Frame: Baseline to 6 months ]

Measure Type Secondary
Measure Title Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)
Measure Description 100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Time Frame Baseline to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   21   24 
Relative Percent Change in Buccal-Cell Neu Protein (ng/mg) 
[Units: Percentage change]
Median (95% Confidence Interval)
 -10.1 
 (-52.3 to 24.6) 
 -4.2 
 (-33.6 to 36.7) 

No statistical analysis provided for Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)



6.  Secondary:   Relative Percent Change in Serum Neu Protein (ng/ml)   [ Time Frame: Baseline to 6 months ]

Measure Type Secondary
Measure Title Relative Percent Change in Serum Neu Protein (ng/ml)
Measure Description 100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Time Frame Baseline to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   19   22 
Relative Percent Change in Serum Neu Protein (ng/ml) 
[Units: Percentage change]
Median (95% Confidence Interval)
 -3.9 
 (-13.5 to 8.1) 
 -8.1 
 (-15.3 to 6.6) 

No statistical analysis provided for Relative Percent Change in Serum Neu Protein (ng/ml)



7.  Secondary:   Relative Percent Change in Protease Activity (Delta RFU/Min/µg)   [ Time Frame: Baseline to 6 months ]

Measure Type Secondary
Measure Title Relative Percent Change in Protease Activity (Delta RFU/Min/µg)
Measure Description 100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Time Frame Baseline to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants who have complete data are analyzed in this outcome measure.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   21   24 
Relative Percent Change in Protease Activity (Delta RFU/Min/µg) 
[Units: Percentage change]
Median (95% Confidence Interval)
 15.7 
 (-23.8 to 74.9) 
 17.2 
 (-10.3 to 30.9) 

No statistical analysis provided for Relative Percent Change in Protease Activity (Delta RFU/Min/µg)



8.  Secondary:   Number of Participants Report at Least 1 Adverse Event During the Study   [ Time Frame: Randomized date to Off-study date, up to 21 months ]

Measure Type Secondary
Measure Title Number of Participants Report at Least 1 Adverse Event During the Study
Measure Description The onset of adverse event is between the randomizaiton date and off-study date
Time Frame Randomized date to Off-study date, up to 21 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Arm I (Bowman-Birk Inhibitor Concentrate)

Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally

laboratory biomarker analysis: Correlative studies

Arm II (Placebo)

Patients receive oral placebo twice daily for 6 months

placebo: Given orally

laboratory biomarker analysis: Correlative studies


Measured Values
   Arm I (Bowman-Birk Inhibitor Concentrate)   Arm II (Placebo) 
Participants Analyzed   67   65 
Number of Participants Report at Least 1 Adverse Event During the Study 
[Units: Participants]
   
Yes: report at least 1 AE   33   25 
No: no AE reported   34   40 

No statistical analysis provided for Number of Participants Report at Least 1 Adverse Event During the Study



9.  Secondary:   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 ]

Measure Type Secondary
Measure Title Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
Measure Description No text entered.
Time Frame Baseline to 6 months  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The participants whose data are available and complete are included in the analysis.

Reporting Groups
  Description
Combined Bowman-Birk Inhibitor Concentrate and Placebo Groups

Patients receive oral Bowman-Birk inhibitor concentrate or Placebo twice daily for 6 months

Bowman-Birk inhibitor concentrate: Given orally Placebo: Given orally laboratory biomarker analysis: Correlative studies


Measured Values
   Combined Bowman-Birk Inhibitor Concentrate and Placebo Groups 
Participants Analyzed   45 
Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months 
[Units: Percentage change]
Median (95% Confidence Interval)
 
Buccal-Cell New   -8.9 
 (-24.5 to 18.5) 
Protease Activity   16.2 
 (-10.0 to 27.0) 
Serum Neu (n=41)   -4.1 
 (-11.3 to 0.7) 


Statistical Analysis 1 for Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
Groups [1] Combined Bowman-Birk Inhibitor Concentrate and Placebo Groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Spearman Rank Correlation
P Value [4] >0.45
Correlation Coefficient [5] 0.11
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Correlation of percent change in buccal-cell Neu with relative percent change in total lesion area
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
Groups [1] Combined Bowman-Birk Inhibitor Concentrate and Placebo Groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Spearman Rank Correlation
P Value [4] > 0.88
Correlation Coefficient [5] 0.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Correlation of percent change in protease activity with relative percent change in total lesion area
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
Groups [1] Combined Bowman-Birk Inhibitor Concentrate and Placebo Groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Spearman Rank Correlation
P Value [4] > 0.66
Correlation Coefficient [5] 0.07
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Correlation of percent change in serum Neu with relative percent change in total lesion area
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[5] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Frank Meyskens, Jr.
Organization: University of California, Irvine
phone: 714-456-6310
e-mail: flmeyske@uci.edu


Publications of Results:
Other Publications:

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00330382     History of Changes
Other Study ID Numbers: NCI-2009-00888
98-34
U01CA072294 ( U.S. NIH Grant/Contract )
First Submitted: May 25, 2006
First Posted: May 26, 2006
Results First Submitted: October 3, 2014
Results First Posted: December 19, 2014
Last Update Posted: December 19, 2014