Imiquimod for Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imiquimod for Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases (NCT00899574), a na phase 2 study. The primary outcome is Objective Response (Complete Clinical Response+ Partial Response).

2. Clinical Question

The registry describes a phase II evaluation of imiquimod, a topical Toll-like receptor 7 agonist, for breast cancer involving the chest wall or skin. Its stated purpose is to assess safety and efficacy in this setting. The primary endpoint is objective response, defined as the percentage of patients who achieved complete clinical response or partial response after the first cycle.

This is a single-group question rather than a comparison of imiquimod with another treatment or with a control group. The endpoint therefore describes response in the patients assessed; it cannot, by itself, distinguish a treatment-associated change from other explanations for what happened during the study. The registry enrollment is 10, while the primary endpoint population is specifically limited to patients who completed the cycle and the week 9 evaluation. The number meeting that endpoint population definition is not reported in the registry record.

The response assessment uses lesion surface area, described as the region of interest, before and after treatment. The endpoint is expressed as a percentage of patients meeting the response criteria, not as an average change in lesion area. The registry identifies the primary assessment timeframe as 9 weeks.

3. Trial Design

This is a phase II, single-group trial sponsored by NYU Langone Health. The registry lists an enrollment of 10 and a completed status. The recorded start is 2009-05, and primary completion is recorded as 2011-04. The allocation field is NA, and the trial is unmasked. There is no randomized or like-for-like control comparison.

The intervention is imiquimod, listed as a drug. The arm description specifies topical imiquimod 5% cream: 1 packet is applied overnight on days 1–5 of each week, with days 6–7 as a rest period. The treatment cycle lasts 8 weeks. The description also says patients with responding or stable local disease, termed non-progressors, may continue on the same schedule; the continuation wording in the registry record is incomplete, so further details are not available.

The primary endpoint is assessed at the end of cycle 1, with the registry specifying a 9-week timeframe. Its stated population consists of patients who completed 1 cycle and had response evaluation at week 9. This definition matters: the enrollment count does not establish how many participants completed treatment or had an evaluable response. Those counts are not reported in the registry record.

The registry lists Clinical Benefits as a secondary outcome and indicates 2 outcome measures, but it does not give results for those measures in the information recorded. It also lists no analyses. A sample-size justification, details of any interim analyses, and a full statistical analysis plan are not reported in the registry record. Consequently, the design description supports an account of the treatment schedule and endpoint, but not a reconstruction of the study’s full analysis procedures.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Patients who completed 1 cycle of treatment (8 weeks) and response evaluation at week 9.

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 Objective Response (Complete Clinical Response+ Partial Response), measured over 9 weeks.

The primary endpoint is the percentage of patients who achieved complete clinical response or partial response at the end of cycle 1. The registry describes the assessment as occurring at 9 weeks, after an 8-week treatment cycle. The endpoint population is patients who completed the cycle and response evaluation at week 9; the number of participants in that population is not reported in the registry record.

Response is assessed using lesion surface area, referred to as the region of interest (ROI), comparing the post-treatment measurement with the pre-treatment measurement. Complete clinical response is defined as absence of any detectable residual disease. Partial response is described as less than 50% of ROI change. The registry attributes these criteria to European Organisation for Research and Treatment of Cancer definitions for chest wall tumors. It does not provide further detail on how individual measurements were converted into the response categories.

A percentage of participants meeting a prespecified response definition can describe how often that outcome occurred in the assessed group. It is different from reporting the average change in ROI: the endpoint counts patients meeting the clinical categories rather than presenting a continuous area-change estimate. The registry identifies a 95% confidence interval as the measure of uncertainty for the percentage, but its numerical limits and the observed response percentage are not reported in the registry record. Without those results, the endpoint’s observed value and precision cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

The primary outcome is a binary response measure at the participant level: a patient either meets the combined complete-or-partial-response definition or does not. The reported quantity is intended to be the percentage of patients with that outcome in the endpoint population. The registry defines that population as patients who completed 1 cycle and response evaluation at week 9. The recorded enrollment of 10 is not necessarily the denominator for this endpoint, because the number completing treatment and evaluation is not reported in the registry record.

General statistical explanation: for a binary outcome, an estimated percentage is based on the number of participants meeting the outcome relative to the number assessed. The estimate is more informative when its denominator is known. In this record, neither the observed response percentage nor the endpoint denominator is reported, so no numerical estimate can be interpreted.

What does the confidence interval add?

The registry identifies a 95% confidence interval as the dispersion measure for the primary percentage, but gives no interval limits. General statistical explanation: a confidence interval presents a range of values compatible with the data under the method used to calculate it. It helps readers judge precision; an estimate alone can conceal whether the underlying data are relatively informative or highly uncertain. A confidence interval does not prove that a result is clinically important, and it does not establish causation.

The calculation method for the interval is not reported in the registry record. Without the interval limits and without the endpoint denominator, it is not possible to evaluate the reported precision or independently check the interval. No recalculated response estimate is available from the registry information.

How should the response definition be read?

The registry describes lesion surface area as the region of interest (ROI) and says response is evaluated as a function of post-treatment over pre-treatment ROI, expressed in percentage. Complete clinical response means absence of any detectable residual disease. Partial response is written as less than 50% of ROI change. The source also says the criteria are based on European Organisation for Research and Treatment of Cancer definitions for chest wall tumors. The record does not give additional operational detail about measurement procedures, how the categories were adjudicated, or how missing measurements were handled.

General statistical explanation: converting measurements into categories can make an endpoint easier to interpret as the proportion of patients meeting a defined response threshold. Categorization also discards information about the degree of change within each category. The registry reports the categorical endpoint, not a distribution of individual ROI changes, so those continuous changes cannot be assessed from this information.

What can a single-group design establish?

The trial is listed as single group, with allocation NA and no masking. There is no concurrent control group in the recorded design. General statistical explanation: a single-group outcome estimate can describe the participants observed, but a comparison group is needed to estimate a between-group treatment contrast directly. Without one, changes over time cannot be separated from other influences using a randomized comparison. Lack of masking can also matter when outcomes involve clinical assessment, although the registry does not report how response assessments were conducted or whether assessors were independent.

The stated sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Those assumptions describe a planning framework, not observed power. The corresponding effect values and participant estimates are not included in the registry information, and the trial itself is single group rather than an equal-allocation, two-arm comparison. A sample-size justification for this trial is not reported in the registry record.

What analysis details remain unknown?

The registry indicates 0 analyses. The specific statistical method used for the response percentage, any adjustment, handling of missing response assessments, and analysis-population rules beyond the stated endpoint population are not reported in the registry record. The record also does not describe interim analyses. General statistical explanation: these choices can affect which observations contribute to an estimate and how uncertainty is quantified. Their absence from the record means the reported endpoint cannot be independently reconstructed from the available information.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Imiquimod")
n      <- c(10)
events <- c(2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Imiquimod  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies Clinical Benefits as a secondary outcome. It does not report the results for the primary or secondary outcomes in the information recorded. It also indicates 0 analyses. The full list of outcome measures, their analysis details, and any relation among their hypotheses are not described.

Multiplicity concerns arise when several outcomes or statistical tests are considered, because the chance of at least one apparently notable result can depend on how many comparisons are made and how they are handled. General statistical explanation: researchers may specify a hierarchy, adjustment, or other strategy to address multiple testing. Whether this trial used such a strategy is not reported in the registry record. A significance level appears among the sample-size planning assumptions, but that alone does not establish the analysis plan or any multiplicity procedure.

The registry defines the primary endpoint population as patients who completed 1 cycle and response evaluation at week 9. It does not report how many participants met that definition, whether any response assessments were missing, or how missing assessments were treated. It also does not give a broader analysis-population definition or specify whether participants who stopped treatment were included in the primary endpoint analysis.

These omissions prevent a reader from determining whether the observed endpoint, if reported elsewhere, would use all enrolled participants or only those with completed assessments. They also prevent assessment of whether missingness could influence the response estimate. The registry record does not report a protocol-based missing-data strategy, an interim-analysis plan, or the statistical analysis plan.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry records 0 participants with serious adverse events among 10 at risk in the imiquimod group. It records 10 participants with other adverse events among 10 at risk. These are participant counts, not a description of the number of individual events, their types, or their severity beyond the serious-versus-other classification.

No serious adverse-event terms are listed. The death count is not reported in the registry record. The other adverse-event count indicates that the registry records affected participants, but it does not specify which events occurred, when they occurred, how long they lasted, or whether they were considered related to imiquimod. Those details are not reported in the registry record.

General statistical explanation: safety counts are most useful when their definitions, observation period, event descriptions, and denominators are clear. The at-risk count gives a denominator for these participant counts, but the registry information does not provide a fuller account of safety follow-up or event-level data. The serious-event count should therefore be read as the recorded count for this group, not as a complete account of every aspect of safety.

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

The registry record describes a phase II evaluation of topical imiquimod in breast cancer patients with chest wall recurrence or skin metastases. It specifies a single-group design, an 8-week treatment cycle, and an objective-response endpoint assessed at week 9. It also records adverse-event participant counts. These registry entries describe the question the trial set out to address and parts of the information collected.

The posted information does not report the observed primary response percentage, its confidence-interval limits, or the number of patients included in the endpoint population. Consequently, it does not establish how often complete or partial response occurred among those assessed, or how precise that estimate was. The enrollment of 10 cannot substitute for the missing endpoint denominator.

Even if a response percentage were available, a single-group result would describe outcomes in the assessed participants rather than estimate a randomized treatment difference. With no control group, the design does not establish what would have happened to comparable patients without imiquimod or under another treatment. The registry information therefore cannot establish that imiquimod caused any observed response or change.

The safety counts indicate that the record lists 0 participants with serious adverse events among 10 at risk and 10 with other adverse events among 10 at risk. Without event names, timing, and further follow-up details, these figures are a limited summary rather than a full characterization of safety. They should be kept separate from the unreported primary efficacy result.

Overall, the record supports a careful account of the trial’s design, endpoint definitions, and recorded event counts. It does not support a conclusion about the magnitude or precision of objective response, a comparison with another treatment, or a complete benefit-and-risk assessment.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how much a registry entry can reveal about a study question while leaving key results unavailable in the record. The population, intervention schedule, endpoint definition, timeframe, and broad design are described. In contrast, the primary response percentage, its confidence interval, the endpoint denominator, and analyses are not reported. That distinction matters: knowing what was planned to be measured is not the same as knowing what was observed.

The single-group design also clarifies the difference between an outcome description and a comparative treatment effect. A response proportion in one group can summarize the experience of the assessed participants, but it does not provide a randomized comparison. Readers need the design context before interpreting any outcome as evidence of a treatment difference or a causal effect.

The endpoint definition illustrates another important statistical issue: a clinical response category depends on how measurements are defined and assessed. The record names lesion surface area, the ROI, and response categories, but does not provide detailed measurement or adjudication procedures. Such details can be important for evaluating reproducibility and understanding what the endpoint captures.

Finally, safety counts and efficacy outcomes answer different questions. The registry records counts for serious and other adverse events, yet those counts do not supply the missing response estimate. Keeping endpoint types, denominators, and missing analysis details distinct helps prevent a limited record from being read as a complete trial report.

15. 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 trial enrolled 10 participants and has a single-group design, with no like-for-like control comparison. This limits the design’s ability to estimate a treatment contrast directly. The registry lists no masking, and the record does not describe who performed response assessments or how assessments were standardized.

The primary endpoint result is not reported in the registry record. Neither its observed percentage nor the numerical limits of the stated 95% confidence interval are available. The number of participants who completed treatment and the week 9 assessment is also not reported, despite that being the endpoint population. Thus, the endpoint denominator and precision cannot be evaluated.

The registry indicates 0 analyses and does not report the statistical analysis plan, missing-data handling, interim analyses, or a sample-size justification. It lists 2 outcome measures but does not provide results for them in the information recorded. The response criteria are described, but further details on ROI measurement, classification, and assessment procedures are not reported.

Safety reporting is limited to participant counts. No serious-event terms are listed, other-event descriptions are not reported, and the death count is not reported in the registry record. The intervention description notes possible continuation for patients with responding or stable local disease, but its wording is incomplete. These limitations leave important questions about endpoint completion, analysis, follow-up, and event detail unresolved.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Imiquimod for Breast Cancer Patients With Chest Wall Recurrence or Skin Metastases — NCT00899574.
• Registry record last updated 2015-12-07; status last verified 2015-11.
• Results first posted 2012-05-11.
• 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.

19. Record Summary

NCT00899574 is a completed phase II, single-group trial sponsored by NYU Langone Health. It enrolled 10 participants with breast cancer involving chest wall recurrence or skin metastases. The intervention was topical imiquimod 5% cream, with an 8-week cycle and response assessment specified at week 9.

The primary endpoint was the percentage of patients achieving complete or partial clinical response among those completing the cycle and evaluation. The registry record does not report the response percentage, confidence-interval limits, or endpoint population size. It records 0 participants with serious adverse events among 10 at risk and 10 with other adverse events among 10 at risk. Further event details, the death count, and analysis procedures are not reported in the registry record.