Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women) (NCT00499083), a na phase 2 study. The primary outcome is Number of Patients With Pathological Complete Response.

2. Clinical Question

3. Trial Design

This was a phase II study registered as NCT00499083, with University of Nebraska listed as sponsor. The record gives a single-group model, allocation as not applicable, and no masking. Enrollment is listed as 17. The study is marked completed; the listed start date is 2006-05-01 and primary completion date is 2009-07-01.

The treatment sequence was neoadjuvant: chemotherapy and intratumoral autologous dendritic cells were given before definitive surgery. In the arm description, patients with HER-2/neu negative tumors received intratumoral dendritic cells one week after the first three of four cycles of dose-dense paclitaxel, followed by four cycles of dose-dense cyclophosphamide and doxorubicin. The record also lists radiation and hormone therapies among the possible post-surgical treatments, including tamoxifen and aromatase inhibition therapy.

The primary outcome was the number of patients with pathological complete response at definitive surgery. The pathologist assessed response using a four-grade description, ranging from disappearance of tumor on microscopic assessment in the breast and lymph nodes to little or no modification of tumor appearance. The record also lists secondary outcomes concerning inflammatory cell infiltration, antibody-dependent cell-mediated cytotoxicity, and the influence of tumor COX-2 and VEGF expression on dendritic-cell-mediated tumor-specific immunity.

A single-group design can describe outcomes observed among treated participants, but it cannot isolate the effect of the dendritic-cell component from chemotherapy, surgery, or other care. No randomized control group or like-for-like comparator is reported. The registry record does not report a statistical analysis plan, participant flow, or the number who contributed data to the primary endpoint.

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

Reasons for not completing this period:

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.

Population: Numbers are based on number of evaluable participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Pathological Complete Response, measured over At definitive surgery..

The primary endpoint is the number of patients with pathological complete response at definitive surgery. It is a count of participants meeting a response definition, rather than a continuous measurement such as tumor size. The institutional pathologist assessed the surgical findings. The registry describes four pathological grades: Grade 1 denotes disappearance of all tumor on microscopic assessment in the breast and lymph nodes; Grade 2 denotes in situ carcinoma only in the breast, no invasive tumor, and no tumor in the lymph nodes; Grade 3 denotes invasive carcinoma with stromal alteration; and Grade 4 denotes no or few modifications of tumor appearance.

Pathological response is used as an early measure of tumor status after neoadjuvant treatment. It is assessed in tissue removed at surgery and can describe how often a specified response category was observed in the treated group. The record does not state precisely which grades are counted as meeting the primary endpoint, beyond naming the outcome pathological complete response and describing the grades. It also does not post the endpoint count or the number evaluated. Thus neither the observed frequency nor its uncertainty can be characterized from the registry record.

This endpoint is distinct from long-term outcomes such as recurrence or survival. The primary endpoint timeframe is definitive surgery; a later clinical benefit is not established by a surgical pathology count alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is a single-group phase II study. In general, a single-group study observes outcomes among participants who receive a treatment strategy without assigning a concurrent control group. Such a design can describe what happened in the enrolled group, but it does not provide the same protection against confounding as randomized allocation. Here, allocation is listed as not applicable, masking as none, and the model as single group. There is therefore no randomized treatment contrast to interpret.

What does a count endpoint tell us?

The primary outcome is a count of participants with pathological complete response at definitive surgery. For a binary outcome, each participant is classified as having or not having the defined event, provided the endpoint definition and analysis population are specified. A count alone does not give the event proportion unless its denominator is also known. The registry record does not report the primary count, the number assessed, or the analysis population, so neither a proportion nor its precision can be stated.

In general, binomial uncertainty reflects the fact that an observed event count is only one realization from a broader range of outcomes that could occur under similar conditions. A confidence interval expresses uncertainty around an estimated event proportion. Its width depends on factors including the amount of information and the observed event frequency. The record does not post a confidence interval for the primary response.

Why does the design matter?

A control group helps estimate what might have occurred under an alternative treatment strategy during the same study period. Without one, an observed outcome cannot be separated from the natural course of disease, other treatments, participant selection, or other influences. This is particularly relevant when several components are delivered: paclitaxel, cyclophosphamide, doxorubicin, dendritic cells, surgery, and possible post-surgical radiation or hormone therapy. A single-group endpoint cannot identify the independent contribution of each component.

No masking is recorded. In general, masking can reduce the influence of expectations on treatment delivery, assessment, or reporting, although surgical pathology may have features that are assessed using defined criteria. The registry record does not say whether pathology assessment was masked or describe procedures to standardize assessment beyond naming the institutional pathologist and listing grade descriptions.

What can the planning illustrations establish?

The registry record describes sample-size planning illustrations based on the observed effect, rather than the trial's own design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was randomized or that it had a two-arm comparator. The registry record does not report a sample-size justification for this trial. Any planning illustration is not observed power and should not be read as a result of the study.

More generally, power is a design-stage probability of detecting a specified effect under specified assumptions. It does not measure the probability that a result is true, and a post hoc calculation based on an observed effect does not repair the absence of an analysis or comparator. No power calculation for the trial itself is reported in the registry record.

How should statistical significance be read?

A p-value, when reported, measures how incompatible the observed data are with a specified null model under the assumptions of the test. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry lists 0 analyses and does not post a p-value for the primary endpoint. There is consequently no reported significance test to interpret. Statistical significance, even if available, would not resolve the limitations of a single-group design.

What is over-dispersion, and does it apply?

In general, over-dispersion occurs when the variability in count data is greater than a chosen model expects. It can make standard errors too small if a model assumes less variability than the data exhibit. The primary endpoint is specified as a participant count for a binary response, not as a repeated event-rate outcome. The record does not report a fitted count model or evidence about over-dispersion; it would be inappropriate to assert that over-dispersion occurred.

The record also names secondary biological outcomes, but does not report their numerical results or analysis methods. Without estimates, denominators, uncertainty measures, and a defined analysis plan, the secondary outcomes cannot be statistically interpreted from this record.

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("Vaccine")
n      <- c(14)
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  Vaccine  14  2  14.3  1.8  42.8  4.0  39.9  4.3  40.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and three secondary outcomes. It does not report a statistical analysis plan, a hierarchy of hypotheses, or a method for controlling multiplicity. When multiple outcomes or comparisons are tested, the chance of at least one false-positive finding can increase; in general, prespecified priorities or an adjustment strategy can help make the interpretation clear. No correction method is reported, so it cannot be assumed that multiplicity was controlled.

The registry lists 0 analyses and does not post a primary endpoint estimate, confidence interval, or p-value. The record therefore does not permit assessment of whether the primary outcome was analyzed as planned, whether secondary outcomes were exploratory, or how any missing endpoint observations were handled.

Enrollment is listed as 17, but the record does not report participant flow, the number who received treatment, the number who reached definitive surgery, or the number with evaluable pathology. It does not describe missing-data methods, exclusions, withdrawals, or an intention-to-treat or per-protocol analysis population. These details matter because the denominator used for a response count affects its interpretation and precision. No denominator should be inferred from the enrollment entry.

The record also does not state whether any interim analyses were planned or conducted, or how the primary endpoint's response grades were mapped to the endpoint classification. Those elements are not reported in the registry record. Consequently, the available information does not establish how multiplicity, missing data, or analysis populations were addressed.

12. Safety Results

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

Deaths

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: febrile neutropenia (33.3%).

The adverse-event entries list a Vaccine group. For serious adverse events, the registry records 3 at risk and 1 affected; for other adverse events, it records 3 at risk and 3 affected. Deaths are listed as 0. Febrile neutropenia is the leading serious adverse-event term, reported as 33.3%.

These figures should be read as the registry's listed safety counts, not as a complete account of every participant's experience. The recorded at-risk numbers are not the same as the enrollment entry, and the registry record does not explain the safety analysis population, event-collection period, or how participants were selected for these entries. The figures should not be generalized to the full enrolled group without that context.

In general, an adverse-event count describes events observed and recorded under a particular collection and reporting process. It does not establish that treatment caused an event. A small or incompletely described safety denominator also limits how precisely event frequency can be understood. The record does not provide further event-level detail, exposure-adjusted rates, or a comparative safety group. Accordingly, the entries describe what is listed in the registry and do not support a comparative safety conclusion.

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

The registry record documents a completed phase II, single-group study of a neoadjuvant treatment sequence that included chemotherapy and intratumoral autologous dendritic cells, with definitive surgery and possible post-surgical radiation or hormone therapy. It identifies pathological complete response at surgery as the primary outcome and describes the pathology grades used to assess response.

It does not report the number of patients with pathological complete response, the denominator assessed, or an uncertainty interval. The primary result cannot therefore be quantified or characterized as precise or imprecise. Absence of a posted result is not evidence of no response, and it is not evidence of a high response. No conclusion about the frequency of pathological complete response can be drawn from the endpoint title alone.

The design also limits what an observed outcome could mean. With no randomized comparator, the study cannot estimate the difference between the treatment sequence and an alternative. Even a reported response count would describe outcomes in the treated group; it would not isolate the contribution of dendritic cells from chemotherapy or other components of care.

The record's safety entries list serious and other adverse-event counts for the Vaccine group and report febrile neutropenia as the leading serious term. Their denominators and relationship to the full enrollment are not explained. These entries are descriptive and do not establish comparative safety or causation.

In short, the record is informative about the study's design, treatment sequence, and intended endpoint, but lacks the primary numerical outcome and important analysis details. It cannot support a quantified efficacy statement, a causal comparison, or a precise account of safety across the enrolled population.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a registered endpoint and a reported result. Naming pathological complete response as the primary outcome tells readers what the study intended to measure, but without the observed count and denominator it does not permit an estimate of response frequency. Without an uncertainty measure, readers also cannot judge how precisely that frequency was estimated.

It also demonstrates why design is central to interpretation. A single-group study can be useful for describing outcomes under a treatment pathway, but it does not create a concurrent counterfactual. The listed regimen combines multiple treatment components and allows post-surgical therapies, so a group-level result would not identify which component was responsible for an outcome. Randomized comparison is needed to support a treatment contrast that is less vulnerable to differences between groups.

The pathology-based endpoint is measured at surgery and is distinct from outcomes observed over longer follow-up. Statistical interpretation must stay aligned with the endpoint actually specified and the time at which it is assessed. A surgical response count cannot, by itself, establish long-term outcomes.

Finally, the record highlights the importance of reporting analysis populations and missing-data handling. Enrollment does not necessarily equal the number with evaluable pathology. Without participant flow, endpoint denominators, analysis methods, and results, readers cannot fully assess precision, potential selection, or the handling of incomplete observations. These reporting details are essential for interpreting both efficacy and safety information.

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 main limitation for statistical interpretation is that the registry record does not report the primary pathological complete response count, its denominator, or an estimate of uncertainty. The stated enrollment of 17 cannot substitute for the endpoint denominator. Participant flow, pathology evaluability, exclusions, and missing-data handling are not reported.

The single-group design has no randomized comparator. It can describe outcomes under the treatment sequence but cannot estimate a comparative effect or separate the effect of dendritic cells from chemotherapy, surgery, and possible post-surgical treatment. The record states that the dendritic-cell intervention was for patients with HER-2/neu negative tumors; the findings, even if posted, would need to be interpreted in that population context.

The record gives a four-grade pathology description but does not specify how those grades map to the primary endpoint classification. It does not report a statistical analysis plan, the primary analysis population, a confidence interval, a test result, or methods for handling multiple outcomes. Although three secondary outcomes are named, numerical results and analysis methods for them are not reported.

The safety entries use at-risk counts that are not reconciled with the enrollment entry, and the record does not explain the safety population or collection period. This prevents a complete interpretation of the adverse-event figures. The record also does not report whether interim analyses were planned or conducted, or give a trial-specific sample-size justification.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Paclitaxel, Cyclophosphamide & Doxorubicin, Autologous Dendritic Cells & Surgery in Stage II/III Breast Cancer (Women) — NCT00499083.
• Registry record last updated 2023-09-29; status last verified 2023-09.
• Results first posted 2018-07-02.
• 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

NCT00499083 is a completed phase II, single-group study sponsored by University of Nebraska. The registry lists enrollment of 17 and a study population of women with stage II or stage III breast cancer. The treatment sequence included paclitaxel, cyclophosphamide, doxorubicin, intratumoral autologous dendritic cells, and definitive surgery; radiation therapy and hormone therapy could follow surgery.

The primary outcome was the number of patients with pathological complete response at definitive surgery. The registry record describes pathology grades but does not report the primary response count, its denominator, or an uncertainty estimate. It lists three secondary outcomes and 0 analyses. Safety entries list a Vaccine group and febrile neutropenia as the leading serious adverse-event term, but the safety population is not explained. The record supports a description of the study design and planned outcomes, not a quantitative primary result or a comparative treatment conclusion.