Lip and Oral Cavity CancerPhase 2NCT00330382
Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia
A Phase 2 study testing Bowman-Birk inhibitor concentrate and laboratory biomarker analysis in people with Lip and Oral Cavity Cancer and Oral Leukoplakia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lip and Oral Cavity Cancer, Oral Leukoplakia, Oropharyngeal Cancer
- What is being tested?
- Bowman-Birk inhibitor concentrate and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 325 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1999to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Medical Center At Irvine-Orange Campus
Orange, California, 92868
About this study
Official title: Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
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
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- Bowman-Birk inhibitor concentrate, placebo, laboratory biomarker analysis
- Medical subject headings
- Mouth Neoplasms, Leukoplakia, Oral, Oropharyngeal Neoplasms, Tongue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bowman-Birk inhibitor concentrateDrug
Also called BBIC
Given orally
placeboOther
Also called PLCB
Given orally
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Bowman-Birk inhibitor concentrate) | Experimental | Patients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months Receives: Drug: Bowman-Birk inhibitor concentrate; Other: laboratory biomarker analysis |
| Arm II (placebo) | Placebo comparator | Patients receive oral placebo twice daily for 6 months Receives: Other: placebo; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Percent Change in Total Lesion Area After 6 Months on Study
Relative percent change in total lesion area was defined as 100 times (area posttreatment minus area pretreatment) all divided by pretreatment area.
Measured: 6 months
Number of Participants by Category of Clinical Response at 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.
Measured: 6 months
Secondary outcomes (7)
The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen
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.
Measured: Baselie to 6 months
Clinical Impression From Photographs
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.
Measured: Baseline to 6 months
Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)
100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Measured: Baseline to 6 months
Relative Percent Change in Serum Neu Protein (ng/ml)
100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Measured: Baseline to 6 months
Relative Percent Change in Protease Activity (Delta RFU/Min/µg)
100% x (Posttreatment value - pretreatment value)/(pretreatment value)
Measured: Baseline to 6 months
Number of Participants Report at Least 1 Adverse Event During the Study
The onset of adverse event is between the randomizaiton date and off-study date
Measured: Randomized date to Off-study date, up to 21 months
Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2006 (estimated)
- Study startJan 1999
- Primary completionJul 2010
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Lip and Oral Cavity CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 325 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Frank Meyskens, Principal investigator, University of California Medical Center At Irvine-Orange Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00330382
- Sponsor's protocol ID
- NCI-2009-00888
- Other IDs
- 98-34, U01CA072294
- Status last verified
- Feb 2014
- First submitted
- 25 May 2006
- Last updated
- 19 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 11795430Meyskens 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.
PubMed 11220668Armstrong 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.
PubMed 23639862Armstrong 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.
PubMed 14520092
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bowman Birk Inhibitor Concentrate and Oral Leukoplakia: A Randomized Phase IIb Trial
- ClinicalTrials.gov ID
- NCT00330382
- Acronym / sponsor ID
- NCI-2009-00888
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 325 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 1999
- Primary completion
- Jul 2010 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 26 May 2006 (estimated)
- Results
- Posted 19 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (Bowman-Birk inhibitor concentrate) | Experimental | Drug: Bowman-Birk inhibitor concentrate, Other: laboratory biomarker analysisPatients receive oral Bowman-Birk inhibitor concentrate twice daily for 6 months |
| Arm II (placebo) | Placebo comparator | Other: placebo, Other: laboratory biomarker analysisPatients receive oral placebo twice daily for 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bowman-Birk inhibitor concentrateAlso: BBICGiven orally | Drug | Arm I (Bowman-Birk inhibitor concentrate) |
| placeboAlso: PLCBGiven orally | Other | Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (Bowman-Birk inhibitor concentrate), Arm II (placebo) |
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.
7 secondary outcomes
The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen
Time frame: Baselie to 6 months
Clinical Impression From Photographs
Time frame: Baseline to 6 months
Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)
Time frame: Baseline to 6 months
Relative Percent Change in Serum Neu Protein (ng/ml)
Time frame: Baseline to 6 months
Relative Percent Change in Protease Activity (Delta RFU/Min/µg)
Time frame: Baseline to 6 months
Number of Participants Report at Least 1 Adverse Event During the Study
Time frame: Randomized date to Off-study date, up to 21 months
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11795430Meyskens 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.
- Background: PubMed 11220668Meyskens 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.
- Results publication: PubMed 23639862Armstrong 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.
- Results publication: PubMed 14520092Armstrong 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Meyskens principal investigator
University of California Medical Center At Irvine-Orange Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bowman-Birk inhibitor concentrate and laboratory biomarker analysis in people with Lip and Oral Cavity Cancer and Oral Leukoplakia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Percent Change in Total Lesion Area After 6 Months on Study (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00330382, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2014.