Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia (NCT00330382), a randomized phase 2 study. The primary outcome is Relative Percent Change in Total Lesion Area After 6 Months on Study.

2. Clinical Question

The trial’s stated aim was to study whether Bowman-Birk inhibitor concentrate could help prevent cancer in patients with oral leukoplakia. The primary outcome measured change in lesion area, rather than cancer incidence. It therefore addresses a change in a lesion measure over the study period, not whether cancer was prevented or how often cancer developed.

The registry describes a randomized Phase II trial and its official title identifies it as Phase IIb. The clinical question is framed around a six-month comparison of the intervention and placebo groups. The reported primary endpoint is a mean, so its group summaries describe average relative lesion-area change among participants with complete data. The registry record does not report a primary cancer-incidence result.

3. Trial Design

This was a randomized, double-masked, parallel-group trial. The registry lists an enrollment of 325 and identifies the study as Phase II; its official title calls it a randomized Phase IIb trial. The study status is completed. The listed start is 1999-01 and the primary completion date is 2010-07. The sponsor was the National Cancer Institute (NCI).

One group received oral Bowman-Birk inhibitor concentrate twice daily for six months, and the other received oral placebo on the same schedule. The primary endpoint timeframe was six months. Randomization, masking, and the parallel-arm structure describe the overall design, but details such as the random-sequence method, allocation concealment, and who was masked are not reported in the registry record.

The primary outcome was analyzed among participants with complete data. Its posted group summaries include 43 participants in the concentrate arm and 46 in the placebo arm. Those outcome-specific counts are distinct from the registry’s enrollment figure; the reason for the difference and a full accounting of participant flow are not reported in the registry record. The reported safety groups have different at-risk counts from the primary outcome groups.

The registry includes seven named secondary outcomes, covering malignancy rating, photograph-based clinical impression, biomarker measures, and adverse events. Numerical results are available for two secondary outcomes in addition to the primary outcome. The registry record does not report the protocol’s planned sample-size assumptions or a detailed statistical analysis plan.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Of 325 consented, 157 (48%) completed the run-in period but 25 declined to continue, resulting in 132 randomized patients.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The participants who have complete data are analyzed in this outcome measure.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Relative Percent Change in Total Lesion Area After 6 Months on Study, measured over 6 months.

The primary endpoint was relative percent change in total lesion area after six months on study. It was defined as 100 times the difference between post-treatment and pretreatment area, divided by pretreatment area. A negative value therefore represents a reduction from the pretreatment lesion area, while a positive value represents an increase. The endpoint is expressed as percentage change, and the registry reports the mean and standard deviation for each group.

Measuring a change in lesion area provides a way to compare the average course of the measured lesions between the two randomized groups over the stated timeframe. It is not itself a count of cancers or a direct measure of cancer prevention. The registry’s rationale describes chemoprevention as an effort to keep cancer from forming, growing, or returning, but the primary endpoint posted for this comparison is lesion-area change.

The analysis population is described as participants who had complete data for this outcome. The registry record does not report how many participants lacked the required measurements, why any data were incomplete, or how missing measurements were handled. Interpretation is consequently limited to the endpoint definition and the complete-data summaries that are posted.

7. Results Posted in the Registry

• Arm I (Bowman-Birk Inhibitor Concentrate): mean -20.60 versus -17.10 on control; difference -3.50 (95% CI -28.27 to 21.27), standardized effect d = -0.06; z-test p = 0.782.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm I (Bowman-Birk Inhibitor Concentrate): mean 1.20 versus 3.60 on control; difference -2.40 (95% CI -10.89 to 6.09), standardized effect d = -0.12; z-test p = 0.579.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm I (Bowman-Birk Inhibitor Concentrate) and the control. The interval gives the range of effects that remain compatible with the data.

Clinical Impression From Photographs

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Arm I (Bowman-Birk Inhibitor Concentrate): mean 4.00 versus 3.60 on control; difference 0.40 (95% CI 0.01 to 0.79), standardized effect d = 0.42; z-test p = 0.045.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Arm I (Bowman-Birk Inhibitor Concentrate) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry names secondary outcomes spanning a change in rated degree of malignancy, clinical impression from photographs, buccal-cell and serum Neu protein, protease activity, adverse events, and a combined biomarker change. Numerical results are posted for two secondary outcome comparisons. The estimates do not point uniformly in one direction: the two comparisons differ in the direction and strength of their statistical evidence. This mixed pattern does not provide a consistent secondary-outcome signal that resolves the uncertainty in the primary lesion-area result.

Secondary endpoints can help describe other aspects of the study, but they do not replace the primary question. Some are measures of clinical appearance or lesion rating, while others are laboratory biomarkers. A change in a biomarker is not automatically equivalent to a change in cancer incidence, and a photograph-based score is not the same measure as total lesion area. The registry’s primary endpoint remains the relative percent change in lesion area after six months.

The two numerical secondary comparisons have unadjusted results. When multiple outcomes are examined, a nominally notable result can occur by chance even if there is no true difference for that outcome. Without a reported multiplicity strategy, secondary findings should be treated as exploratory rather than as definitive confirmation. The registry record does not report whether the investigators designated particular secondary results for confirmatory testing.

Several named secondary outcomes do not have numerical comparison results in the posted material described by the registry record. Their absence should not be interpreted as evidence of no difference. The full set of secondary outcomes also cannot be treated as a complete picture of all measured results when numerical results are not reported for each one. Taken together, the secondary information adds context but does not remove the primary result’s broad uncertainty or establish a cancer-prevention effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• The Difference in Rated Degree of Malignancy Between Randomization and 6-month Specimen
• Clinical Impression From Photographs
• Relative Percent Change in Buccal-Cell Neu Protein (ng/mg)
• Relative Percent Change in Serum Neu Protein (ng/ml)
• Relative Percent Change in Protease Activity (Delta RFU/Min/µg)
• Number of Participants Report at Least 1 Adverse Event During the Study
• Combined Percentage Change From Baseline in Proteolytic Activity, Buccal-cell Erb-B2 (Neu) and Serum Levels of Neu at 6 Months

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean summarize? The primary endpoint is continuous, and the registry reports a mean for each treatment group. A mean represents the arithmetic average of the observed values in that group. For this endpoint, each value is a relative percent change in total lesion area. The mean does not describe every participant’s result, and a group average can coexist with substantial variation among participants.

The reported standard deviation describes how dispersed the observed values are around the group mean. The standard deviations were 52.4 in the concentrate group and 66.4 in the placebo group. A larger standard deviation indicates more spread in the observed values, but it does not by itself indicate whether the group mean is estimated precisely. The number of observations also affects precision.

What is the mean difference? The comparison is the mean in the concentrate group minus the mean in the placebo group. The posted estimate is -3.5. Its negative sign indicates that the concentrate-group mean was lower on this change scale. Because negative relative change represents a decrease in lesion area, the estimate’s direction is toward a larger average decrease in the concentrate group. This describes the direction of the estimate, not proof of a treatment effect.

What does a confidence interval express? General explanation: a confidence interval gives a range of values compatible with the data under the statistical method used. It communicates uncertainty around an estimate rather than a guarantee that the true value lies within the particular interval. The interval for the primary mean difference is -28.27 to 21.27. Because it spans zero, the data are compatible with no mean difference as well as differences in either direction. The method used to construct this interval is not reported in the registry record.

How should the p-value be read? The unadjusted p-value for the primary comparison is 0.782. General explanation: a p-value measures how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The exact test and model used for this reported p-value are not reported in the registry record.

The word unadjusted matters because the value has not been described as corrected for examining multiple outcomes or comparisons. The registry lists several secondary outcomes, and multiple analyses can increase the chance that at least one result appears notable by chance. Whether the investigators used a multiplicity procedure in their planned analysis is not reported in the registry record. The posted p-value should therefore be read as an unadjusted result, not as a documented multiplicity-controlled finding.

Why can spread affect a comparison? General explanation: when participant outcomes vary widely, a group mean can be difficult to estimate precisely, particularly when the number of observations is limited. Over-dispersion, meaning variability greater than assumed by a particular model, can make model-based uncertainty estimates too small if the model does not account for it. The registry reports standard deviations but does not report a distributional assessment or a specific model for the primary comparison, so no claim about over-dispersion or model adequacy can be made from the registry record.

The endpoint population is participants with complete data. This identifies who was included by the stated outcome description, but it does not explain whether missingness was related to treatment, outcome, or other factors. The registry record does not report imputation, sensitivity analyses, an intention-to-treat analysis, or other missing-data methods. Nor does it report the exact statistical analysis plan or whether the analysis was prespecified in the form posted.

Randomization is intended to support a fair comparison between assigned groups, while masking can reduce certain forms of expectation or assessment bias. General explanation: these design features do not remove uncertainty from a small endpoint analysis or resolve missing-data concerns. The registry identifies the study as randomized and double-masked, but does not report the procedures used to implement those features. The estimates and uncertainty should be interpreted with that level of methodological detail in mind.

11. Confidence Intervals and Precision

The primary mean difference was -3.5, with a confidence interval from -28.27 to 21.27. This interval is broad and includes zero. It allows for a range of plausible group differences, including a decrease in lesion area that is larger on average in the concentrate group, little or no mean difference, or a difference in the opposite direction. The point estimate alone does not convey this uncertainty.

The interval’s breadth should be considered alongside the primary endpoint group sizes: 43 participants in the concentrate group and 46 in the placebo group. The group standard deviations, 52.4 and 66.4, indicate substantial variation in the observed relative changes. Together, these features help explain why the estimated difference is not precise enough to distinguish among a wide range of possible effects. The registry record does not report a prespecified threshold for a clinically important difference, so the interval cannot be judged against such a threshold from the posted information.

The unadjusted p-value of 0.782 is consistent with the interval’s inclusion of zero, but a p-value and a confidence interval answer different questions. The p-value summarizes evidence against a specified null under a statistical model; the interval displays uncertainty about the size and direction of the difference. Neither result proves equivalence or rules out meaningful differences. The confidence-interval method and test method are not reported in the registry record.

Precision is also relevant to the interpretation of the complete-data analysis. The registry does not report why endpoint data were unavailable for participants outside the analysis groups or whether missingness could affect the estimated difference. Uncertainty from missing outcomes is not captured merely by the confidence interval around the reported complete-data comparison.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. These assumptions describe the illustration; the trial’s own original sample-size assumptions are not reported in the registry record.

For the primary outcome, the figures are participants per arm, not total participants or total events. For example, planning for 100% of the observed effect gives 4,621 participants per arm for 80% power and 6,187 participants per arm for 90% power. The 80% column represents a design that would detect the specified effect in 80% of repeated studies under the stated assumptions if that effect were the true one. The 90% column represents a higher chance of detecting that same specified effect, again under those assumptions.

Rows for 75% and 50% of the observed effect ask what would be needed to detect smaller effects relative to the observed estimate. Smaller effects are harder to distinguish from random variation, so the planning figures require more participants per arm. The sample-size curve is another way to read this relationship between the assumed effect and the corresponding planning requirement; it does not change the assumptions underlying the figures.

These are planning illustrations, not observed power. They do not describe the power the completed trial actually had, and they are not evidence that a result is true or false. In particular, the illustrations use an observed effect as their starting point, so they should not be mistaken for the study’s prospectively chosen design target.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -3.500; pooled standard deviation σ = 60.050.
2. n = 2 × (1.96 + 0.842)² × 60.050² / -3.500² = 4,621.0, rounded up to 4,621 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3.5                      # observed difference in means
sigma <- 60.0502777851108                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(330382)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 4,621 (80% power), 6,187 (90% power)
 75% of observed effect: n per arm = 8,216 (80% power), 10,998 (90% power)
 50% of observed effect: n per arm = 18,484 (80% power), 24,745 (90% power)
power.t.test: 4621.9 
Simulated power at n = 4,621 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists seven secondary outcomes, in addition to the primary outcome, and reports nine outcome measures overall and three analyses. Numerical secondary comparisons are available for two outcomes. Examining several outcomes raises a multiplicity issue: the more statistical comparisons made, the greater the possibility that at least one will look unusual by chance, even when no true effect exists for the measures being tested.

The posted secondary p-values are unadjusted. The registry record does not report whether the original analysis plan specified a correction for multiple comparisons, a hierarchy of outcomes, or another strategy to control the overall error rate. It also does not report whether the posted outcome set reflects all planned outcomes or all analyses performed. Consequently, the strength of the secondary evidence cannot be assessed as if a prespecified multiplicity procedure had been documented.

The primary endpoint description states that participants with complete data were analyzed. The registry record does not report the amount or reasons for missing primary endpoint data, the handling of missing values, or sensitivity analyses testing the effect of missingness. It does not report whether participants were analyzed according to randomized assignment for this outcome. The outcome-specific analysis groups are therefore best understood as the reported complete-data groups, not assumed to be a full intention-to-treat population.

The registry identifies randomization, double masking, and a parallel-group design, but the sequence-generation procedure, allocation concealment, masking implementation, and analysis methods are not reported in the registry record. The exact test underlying the p-value, the confidence-interval method, and any covariate adjustment are also not reported. These omissions limit the ability to evaluate the analysis beyond the summary estimates and design labels.

The original trial sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record. The planning illustrations based on the observed effect are not substitutes for those original design details. Without the original plan and complete participant-flow information, it is not possible to determine from the registry alone how closely the posted analyses followed the investigators’ intended procedures.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: admission for oral surgery on floor mouth (1.5%), c/o "lump" to rt. lower gum (1.5%), cold (1.5%), epigastric pain (1.5%), finger infection - left ring (1.5%).

The serious adverse event figures are reported for groups of 67 participants at risk in the Bowman-Birk inhibitor concentrate arm and 65 at risk in the placebo arm. Five participants in the concentrate group and zero in the placebo group were reported as having at least one serious adverse event. These are counts of participants affected, not counts of all serious-event episodes. Deaths are not reported in the registry record.

The record also reports other adverse events in 30 participants at risk in the concentrate group and 25 in the placebo group. The serious and other adverse-event figures are separate categories and should not be combined. The listed serious-event terms each have a reported frequency of 1.5%: admission for oral surgery on floor mouth, complaint of a lump to the right lower gum, cold, epigastric pain, left ring finger infection, and heart problems.

These figures describe events reported during the study; they do not establish that an event was caused by the assigned intervention. The registry record does not provide a causal assessment for these terms or the detailed event-level context needed to interpret them. Safety counts also use different at-risk group sizes from the complete-data primary endpoint groups, so the denominators should not be interchanged.

16. What the Result Does, and Does Not, Mean

The primary estimate describes the average difference in relative lesion-area change between the concentrate and placebo groups among participants with complete data. Its direction favors a larger average decrease in the concentrate group, but its confidence interval is broad and includes differences in either direction. The unadjusted p-value does not provide strong evidence against a zero mean difference. Together, these statistics leave substantial uncertainty about the size and direction of the group difference.

That statistical reading is narrower than the trial’s cancer-prevention aim. The primary outcome was lesion area after six months, not the occurrence of cancer. A lesion-area change can be informative about the measured outcome, but it cannot by itself establish whether cancer was prevented. The registry record does not report a primary cancer-incidence result, and the posted material does not establish longer-term effects beyond the six-month endpoint.

The result also does not establish that the groups are equivalent. Failure to find strong evidence of a difference is not the same as demonstrating that any difference is sufficiently small to be unimportant. The confidence interval contains a wide range of possibilities, and the registry record does not report a threshold for a clinically important difference against which to judge that range.

Secondary outcomes include clinical ratings and biomarkers, but unadjusted findings across several measures have a higher risk of chance-positive results. The secondary pattern does not resolve the primary uncertainty, and missing numerical results for some named outcomes should not be read as evidence of no effect. Safety event counts describe what was reported, not whether the intervention caused those events.

Overall, the posted data support a cautious description of an uncertain six-month comparison in lesion-area change. They do not support a broader claim that the intervention does or does not prevent cancer, and they do not answer questions about effects outside the measured population, outcome, and timeframe.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated difference should be read together with its uncertainty. The primary point estimate has a direction, but the confidence interval spans zero and extends to differences in both directions. A single mean difference cannot show how precisely the study distinguishes a real group difference from variation in participant outcomes.

The outcome also highlights the difference between a clinical aim and the endpoint used to evaluate it. The stated aim concerns cancer prevention, while the primary endpoint is relative change in total lesion area over six months. These are related in the broad context of oral leukoplakia, but they are not interchangeable statistical outcomes. A result for lesion area should not be presented as a direct estimate of cancer prevention.

Participant counts require careful reading as well. The registry lists enrollment of 325, whereas the complete-data primary outcome groups contain 43 and 46 participants. The registry record does not account for this difference. A reader should not treat enrollment as the number contributing to every outcome or assume that the endpoint groups represent all enrolled participants.

The registry also names a range of secondary clinical and biomarker measures. Their mixed pattern and unadjusted status demonstrate why multiple outcomes need an interpretable analysis plan. Without a reported multiplicity strategy, individual secondary findings have limited confirmatory weight. The posted sample-size illustrations offer another statistical lesson: planning requirements depend strongly on the effect size one wants to detect, and illustrations based on an observed effect are not the trial’s original design justification.

These issues are common in clinical-trial interpretation: distinguish endpoint from clinical aim, estimate from precision, enrollment from analysis population, and exploratory findings from confirmatory evidence. Applying those distinctions keeps the conclusions aligned with what the registry actually reports.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for interpreting the primary result is the broad confidence interval around the mean difference. It includes zero and allows for differences in either direction. The registry record does not report a clinically important difference threshold, so the practical importance of the range cannot be judged from a prespecified benchmark.

The primary analysis includes only participants described as having complete data. The registry lists enrollment of 325, while the endpoint groups contain 43 and 46 participants. Participant flow, reasons for missing endpoint data, and missing-data methods are not reported in the registry record. This prevents assessment of whether the complete-data analysis could differ from an analysis of all randomized participants.

The outcome is a six-month change in total lesion area, not cancer incidence. The registry record does not report a primary result for cancer development or a longer-term outcome that would directly answer the prevention question. The available endpoint therefore limits conclusions to the measured change over the stated period.

The registry names multiple secondary outcomes, but numerical secondary comparisons are available for only two in addition to the primary outcome. The reported secondary p-values are unadjusted, and the multiplicity plan is not reported. The statistical test, interval-construction method, detailed analysis plan, original sample-size justification, and any interim analyses are also not reported in the registry record.

Safety reporting gives counts of affected participants and selected event terms, but does not provide event-level causal assessments in the information reported. The safety at-risk counts differ from the primary endpoint analysis counts. These features limit cross-comparison and causal interpretation of the adverse-event summaries.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Bowman-Birk Inhibitor Concentrate in Preventing Cancer in Patients With Oral Leukoplakia — NCT00330382.
• Registry record last updated 2014-12-19; status last verified 2014-02.
• Results first posted 2014-12-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

The registry describes a completed randomized, double-masked, parallel Phase II trial sponsored by the National Cancer Institute. Its official title identifies it as a Phase IIb trial. Enrollment was 325; the listed start was 1999-01 and primary completion was 2010-07.

Participants received oral Bowman-Birk inhibitor concentrate or oral placebo twice daily for six months. The primary endpoint was mean relative percent change in total lesion area among participants with complete data. The posted mean difference was -3.5, with a confidence interval from -28.27 to 21.27 and an unadjusted p-value of 0.782.

The registry lists seven secondary outcomes, with numerical comparisons posted for two. The primary result is imprecise and does not directly measure cancer incidence. Details on participant flow, missing-data handling, multiplicity, and the original statistical plan are not reported in the registry record.