Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer (NCT00542191), a na phase 2 study. The primary outcome is 1) Pathologic Response.

2. Clinical Question

3. Trial Design

This was a phase II, single-group trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer. The arm description names metronomic AC followed by weekly TC and then surgery. The listed interventions include doxorubicin, cyclophosphamide, paclitaxel and carboplatin, along with definitive surgery and radiotherapy. The record does not establish the full treatment schedule, doses, eligibility criteria, or the timing and use of each listed intervention.

The registry lists allocation as not applicable, masking as none, and the study model as single group. Thus, the design has no randomized control arm and does not support a randomized between-group estimate. The intended role described in the brief summary was to gather information about primary-tumor and axillary lymph-node response to primary chemotherapy, alongside disease-free and overall survival outcome data, for use in building subsequent trials. The posted primary outcome, however, is pathologic response; survival results are not reported in the registry record.

Enrollment is listed as 30. That figure should not be read as the number who received the full regimen, underwent surgery, or had an evaluable primary outcome: the registry does not report those analysis counts. The primary-outcome population description states that the study closed to accrual because there were not enough participants to participate. The status is terminated. The record gives a start of 2007-07 and a primary completion date of 2016-08-02, but does not report the reason for termination beyond the accrual statement.

The registry lists one outcome measure and no analysis entries. It does not report a protocol-level statistical plan, a sample-size justification, or whether any interim analyses were planned or conducted. Those omissions limit what can be inferred about how the study was designed to estimate response or how investigators intended to interpret the results.

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:

Analysis population for the primary outcome, as defined in the registry: Study closed to accrual - not enough participants to participate.

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: Slow accrual

6. Primary Endpoint

The registry lists the primary outcome as 1) Pathologic Response, measured over Upon completion therapy after surgery.

The primary endpoint is titled pathologic response. It is recorded as a count of participants and described as a pathologic measurement of viable primary tumor mass after surgery, with assessment upon completion of therapy after surgery. In neoadjuvant treatment, surgery makes it possible to examine the tumor remaining after systemic treatment. A pathologic measure can therefore describe tumor findings at the time of operation rather than relying only on symptoms or imaging.

The registry does not define a threshold for classifying a participant as having a response, specify whether the measure is a continuous tumor mass or a categorical outcome, or explain how lymph-node findings contribute to the primary endpoint. Although the brief summary mentions primary-tumor and axillary lymph-node response, the primary-outcome description refers specifically to viable primary tumor mass. The record does not clarify this difference.

The outcome is listed as a participant count, but no response count or analysis result is posted. The outcome population description says the study closed to accrual because there were not enough participants to participate. Therefore, the registry record identifies the intended endpoint but does not provide the result needed to describe the observed response rate or the distribution of tumor measurements. No estimate of precision can be drawn from the posted primary-outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines which statistical conclusions are available. This study is listed as a single-group phase II trial, with allocation not applicable and no masking. A single-group design can describe outcomes among participants who receive the study regimen, if those outcomes and their denominators are reported. It cannot provide a randomized comparison with an alternative regimen. A before-and-after interpretation would also require measurements and analysis details that are not reported in the registry record.

What a participant count can tell readers

The primary outcome is categorized as a count of participants. For a binary outcome, a count is interpretable only with a clear definition of the event and an appropriate denominator. Here, the endpoint description refers to viable primary tumor mass, but the registry does not state a categorical response definition or post an outcome count. It also does not report how many participants were eligible for, received, or completed the relevant assessment. Without those elements, the outcome cannot be converted into a response proportion or otherwise summarized from the record.

A confidence interval, in general, describes the uncertainty around an estimate under a specified statistical model. It does not show the range of individual participant outcomes, and it does not correct for bias or missing information. No confidence interval or endpoint estimate is posted for this primary outcome, so its statistical precision cannot be assessed.

Why the comparator matters

In a randomized comparison, treatment groups can be compared using a prespecified outcome and analysis, subject to the design and limitations of the trial. In this single-group study, there is no randomized control group. An observed pathologic finding could characterize the treated group if it were reported, but without a comparator it would not establish how that finding differs from an outcome under another treatment. The registry does not provide an adjusted or unadjusted comparative estimate.

Planning calculations and power

General sample-size illustrations can show how a hypothetical study might be planned under stated assumptions. They are not observed power, do not recover results that are absent, and do not demonstrate that a study was adequately sized. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect specified as a fraction of an observed effect. Time-to-event illustrations are described in terms of total events; other illustrations are described in participants per arm. Those assumptions describe planning illustrations, not the design of this single-group trial. The registry record does not report the trial's own sample-size justification or a result from which an observed effect for these illustrations could be evaluated.

In general, over-dispersion occurs when variability in the data is greater than a model assumes. Ignoring it can make uncertainty appear too small. The registry does not report an analysis model, dispersion estimate, or evidence that over-dispersion was relevant to this endpoint. No conclusion about model fit can therefore be drawn.

What the analysis record contains

The registry lists one outcome measure and no analysis entries. This means no analysis result is posted in the registry; it does not establish whether an analysis was conducted outside the record. Statistical methods, covariate adjustments, confidence intervals, hypothesis tests, and any prespecified decision rule are not reported in the registry record. Likewise, the record does not state whether analyses were interim or final, or whether any sensitivity analyses were performed. The dates and status alone do not supply those missing methods.

These distinctions matter because an outcome label, a study design, and an analysis result are different kinds of information. The endpoint describes what investigators intended to measure; the design describes how participants were allocated; and an analysis would quantify the observed data using specified methods. The registry record contains the first two types of information but no posted primary-outcome analysis. Statistical interpretation should therefore stop short of estimating response or treatment effect.

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("Single Arm Study; Taxol, XRT, Gemzar and Carbo")
n      <- c(18)
events <- c(15)
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  Single Arm Study; Taxol, XRT, Gemzar and Carbo  18  15  83.3  58.6  96.4  60.8  94.2  60.4  93.9

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when several outcomes, comparisons, time points, or analyses create more than one opportunity to identify a result as statistically notable. The registry lists one outcome measure and no analysis entries. It does not report whether other outcomes were prespecified in a protocol, whether multiple tests were planned, or whether any adjustment for multiplicity was used. The brief summary mentions disease-free and overall survival data as aims, but the posted results do not include those outcomes. A multiplicity strategy is not reported in the registry record.

Missing-data handling is also not described. The record does not say how participants without surgery, without a pathologic assessment, or with incomplete follow-up would be treated in an analysis. It does not provide an endpoint denominator, the number assessed, or reasons for any missing outcome data. The statement that the study closed to accrual because there were not enough participants to participate provides context about accrual, but it does not define the analysis population or explain missingness at the participant level.

The record does not name an intention-to-treat, per-protocol, safety, or other analysis population for the primary outcome. It also does not describe sensitivity analyses to examine the effect of missing data. These details should not be inferred from the listed enrollment or trial phase. Because no primary analysis is posted, there are no multiplicity adjustments or missing-data assumptions to evaluate against an observed result.

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 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: sepsis (9.5%), pulmonary embolus (4.8%).

The registry reports safety figures for a group labeled “Single Arm Study; Taxol, XRT, Gemzar and Carbo.” It lists 21 participants at risk for serious adverse events and 3 affected; for other adverse events, it lists 21 at risk and 0 affected. It also lists 3 deaths. The most frequently listed serious terms are sepsis at 9.5% and pulmonary embolus at 4.8%.

These figures should be read as registry counts and listed percentages, not as proof that a treatment caused an event. The record does not provide event narratives, timing, severity details beyond the serious-event category, or an assessment of attribution. It does not say whether participants could have more than one event or whether the listed terms overlap with the overall affected count. The cause of the deaths is not reported in the registry record.

The safety group label differs from the arm description, which names metronomic AC followed by weekly TC and surgery. The registry does not explain the label difference or establish how the safety population relates to the described treatment sequence. The figures therefore require caution when linking them to a particular regimen component. The record also does not report a comparative safety analysis, and the single-group design has no control arm for estimating relative risk.

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

The record establishes that this was a phase II, single-group trial focused on neoadjuvant chemotherapy for triple-negative breast cancer, and that pathologic response was the primary listed outcome. It also records that the study was terminated and that the primary-outcome population description attributes closure to insufficient participant accrual. These are important details about the study's design and status.

The record does not establish the number of participants with a pathologic response, the magnitude of viable tumor remaining, or the precision of any endpoint estimate. Enrollment is listed as 30, but the number with evaluable outcome data is not reported. No primary-outcome analysis is posted. Consequently, the registry information does not support a conclusion about the observed response in the study group.

Nor does the record establish a comparative treatment effect. The trial has no randomized comparator, and no control-group result or comparative estimate is reported. An outcome in one group, even if available, would not by itself show what would have occurred under another regimen. The registry does not post disease-free or overall survival results, despite their mention as data-gathering aims in the brief summary.

The safety entries describe reported counts and terms, but their group label differs from the stated treatment arm and the record does not establish causation. The counts should not be interpreted as a complete comparison of harms or as a definitive attribution to the regimen. In short, the posted record describes a research question, design, and limited safety information; it does not provide the primary efficacy result needed to quantify response or determine a treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a registry record needs more than a named endpoint to support interpretation. The primary outcome is identifiable, and the single-group design is explicit, but no outcome analysis is posted. Readers can distinguish the intended measurement from evidence about the observed result: the former is present, while the latter is not.

The accrual statement also matters. A planned or listed enrollment figure is not automatically the number of participants who contribute to an endpoint. The record lists enrollment as 30 while noting that accrual closed because there were not enough participants to participate. Without an analyzed denominator, outcome completeness, or a reported estimate, readers cannot assess how much information the study generated for its primary question.

The design illustrates another basic principle: a single-group study can provide descriptive information, but it does not create a randomized contrast. The brief summary describes a goal of gathering response and survival data to inform later trials. That intended role is distinct from demonstrating a treatment effect, and the registry does not post the data needed to assess either response or survival.

Finally, the difference between the stated treatment arm and the safety-group label highlights the value of clear population and intervention reporting. When records do not explain how safety data map to a regimen, readers should avoid assuming that the entries describe precisely the same treatment exposure. These limitations are not repaired by statistical calculation; they identify what information a complete report would need to clarify.

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.

Several trial-specific limitations constrain interpretation. The study is single group, so it has no randomized comparator. The registry lists allocation as not applicable and masking as none. Without a control arm, the record cannot support a randomized estimate of how outcomes differ from another treatment strategy.

The primary endpoint is not fully operationalized in the posted record. It is described as pathologic response and as viable primary tumor mass after surgery, but no response threshold, measurement scale, or role for axillary lymph-node findings is specified. The brief summary mentions both primary-tumor and axillary lymph-node response, leaving the relationship between those aims and the posted primary endpoint unclear.

The record lists enrollment as 30, but does not report the number treated, the number undergoing surgery, or the number with evaluable outcome data. The population description notes insufficient participant accrual, while the study status is terminated. The registry does not explain the termination in further detail or report whether an outcome analysis was completed elsewhere. It gives no primary result, analysis entries, or estimate of precision.

The intervention information is also incomplete for interpreting exposure. The arm description names metronomic AC followed by weekly TC and surgery, while the intervention list includes multiple drugs, definitive surgery and radiotherapy. Exact schedules, doses, adherence, treatment modifications, and radiotherapy timing are not reported in the registry record. The safety-group label differs from the arm description, with no explanation of the difference.

Finally, the record does not report eligibility details, a statistical analysis plan, a sample-size justification, interim analyses, missing-data procedures, analysis populations, or longer-term outcome results. These are specific gaps in the posted information, not grounds to assume that a particular method or result was used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer — NCT00542191.
• Registry record last updated 2021-05-26; status last verified 2021-05.
• Results first posted 2019-09-10.
• 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

The registry record describes a phase II, single-group trial of neoadjuvant metronomic chemotherapy for triple-negative breast cancer. Its arm description specifies metronomic AC followed by weekly TC and surgery. The record lists enrollment as 30, identifies pathologic response after therapy and surgery as the primary outcome, and states that the study was terminated. The primary-outcome population description says accrual closed because there were not enough participants to participate.

No primary-outcome result or analysis is posted. The record does not report an evaluable denominator, response definition, confidence interval, or survival result. Safety entries list 21 at risk and 3 affected for serious adverse events, 21 at risk and 0 affected for other adverse events, and 3 deaths; the safety-group label differs from the stated arm description. These data describe the registry entries but do not establish comparative effects or causal attribution.