Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer (NCT00820872), a na phase 2 study. The primary outcome is Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0.

2. Clinical Question

The trial is described as a phase II safety study. Its stated purpose is to study side effects of the four-drug regimen in early stage breast cancer. That makes the primary question a safety question about the frequency of a specified adverse event, rather than a comparison of treatment effects against another regimen or a control group.

The registry lists an enrollment of 30, but does not report how many participants were evaluable for the primary endpoint. Nor does it report the number who experienced grade 3 or 4 diarrhea. Without the numerator and the relevant evaluable denominator, the posted record does not permit a direct estimate of the endpoint proportion or its precision. The separate adverse-event summary reports event counts, but those entries do not supply the missing primary-endpoint result.

3. Trial Design

This is a phase II study with a single-group model. The registry marks allocation as not applicable and masking as none. Accordingly, the record describes an open-label, nonrandomized study without a concurrent control arm. Its design is not suitable for a randomized comparison between the regimen and another treatment.

The listed enrollment is 30. The study status is completed, with a start date of 2009-02 and a primary completion date of 2010-12. The sponsor is the Alliance for Clinical Trials in Oncology. The condition listed is breast cancer, and the study title and brief description focus on patients with early stage disease.

Participants in the described regimen received docetaxel and carboplatin intravenously on day 1, trastuzumab intravenously on days 1, 8, and 15, and oral lapatinib ditosylate on days 1–21. Treatment is described as repeating every 3 weeks for 6 courses. The regimen description is truncated after its reference to disease progression, so further details about treatment discontinuation are not reported in the registry record.

The primary outcome listing concerns the proportion of patients experiencing grade 3 or 4 diarrhea, measured by NCI CTCAE v3.0, with a timeframe of up to 10 years. The specified population is all evaluable patients. The record lists one outcome measure, but does not post a result or an analysis for that endpoint. The enrollment count should therefore not be treated as the endpoint denominator, and the record does not establish how many participants contributed to the endpoint assessment.

A single-group safety study can describe events observed during treatment and follow-up, but it cannot by itself separate events associated with the regimen from events that might also occur without it or under another treatment. That limitation follows from the absence of a concurrent comparator, not from a statistical adjustment that could be applied to the reported event counts.

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: All evaulable patients

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 Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0, measured over Up to 10 years.

The primary endpoint is the proportion of patients experiencing grade 3 or 4 diarrhea, measured using NCI CTCAE v3.0. It is a binary outcome at the participant level: a participant either meets the specified event definition during the assessment period or does not. Expressing the result as a proportion is intended to describe how often this defined safety event occurred in the endpoint population.

Severity grading makes the endpoint narrower than a count of any diarrhea. In general, adverse-event grading systems classify events by severity; this endpoint focuses on the stated higher grades rather than all reported diarrhea. The registry’s timeframe is up to 10 years, but the record does not provide further detail about the timing of assessments or how follow-up was handled.

A proportion is interpretable only alongside its numerator, denominator, and uncertainty. The denominator should correspond to the population assessed for the endpoint, which the record calls all evaluable patients. The number evaluable, the number meeting the endpoint, and a confidence interval are not reported in the registry record. The enrollment count alone cannot fill in those details.

This endpoint fits the stated safety purpose because it focuses on a defined adverse event and its severity. It does not measure tumor response, disease control, or comparative benefit. The posted registry record does not report the primary endpoint result, so the frequency and precision of grade 3 or 4 diarrhea cannot be assessed from that outcome listing.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted record contains a single-group design and a binary primary endpoint, but no primary endpoint analysis. General statistical concepts can clarify what would ordinarily be needed to interpret such an outcome, while not filling in results that are absent from the registry record.

How is a binary endpoint summarized?

For a binary endpoint, the basic summary is the number of participants meeting the event definition divided by the number assessed for that endpoint. The resulting proportion describes the observed frequency in the defined analysis population. Here, the endpoint is grade 3 or 4 diarrhea under NCI CTCAE v3.0, and the stated population is all evaluable patients. Neither the endpoint numerator nor the evaluable denominator is reported in the registry record, so the endpoint proportion cannot be recovered from the outcome listing.

The enrollment count and the denominator are not interchangeable by default. Enrollment describes the number entered into the study; an endpoint denominator describes participants with information contributing to that endpoint under the analysis approach. The registry record does not report whether all enrolled participants were evaluable, why any participant might not have been evaluable, or how incomplete observations were handled.

What does uncertainty add?

A confidence interval is a range of values that reflects the statistical uncertainty around an estimate under a specified method. For an event proportion, its width depends in part on the number of observations and the observed event frequency. A point estimate alone would not show how precisely the frequency is estimated. The record does not report a confidence interval for the primary endpoint, and its missing numerator and denominator prevent a reader from assessing that precision.

In a single-group study, the proportion would describe the observed event frequency in that study population and observation context. It would not be a treatment effect relative to a control group. A between-group risk difference or ratio requires a comparison group and corresponding outcome data. Neither is part of the listed trial design.

What does the design permit?

Allocation is marked not applicable, masking is none, and the model is single group. These features identify a nonrandomized, unmasked study without a concurrent control arm. A descriptive safety summary may be useful for documenting events, but potential differences in participant characteristics, background event rates, observation, and reporting cannot be disentangled through a randomized comparison that this design does not include. The registry record does not report a statistical plan for adjusting for such factors.

Blinding can sometimes reduce the influence of knowledge about treatment on assessment or reporting. In this study masking is listed as none. That fact alone does not show that assessments were biased; it identifies a design feature relevant to interpretation. The record does not report procedures intended to limit or assess possible influence on event evaluation.

How should the adverse-event counts be read?

The adverse-event summary separates serious events from other events and gives participants at risk and affected for each category. Such counts describe the registry’s categorized event data. They do not give the primary endpoint result unless the endpoint definition and population match, and the record does not establish that match. A serious adverse event is a classification based on seriousness criteria; a grade 3 or 4 event is a severity classification under the named grading system. These classifications answer different questions and should not be treated as equivalent.

The serious-event terms are reported as percentages. The registry does not provide associated event-specific numerators in the listed summary, and participants can experience more than one event term. Consequently, term percentages should not be summed to create a total or translated into counts without information that the record does not report. The absence of a death count is also not evidence of no deaths; the death field is not reported in the registry record.

What do the planning illustrations mean?

The sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. The record labels non-time-to-event planning outputs as participants per arm for 80% power or other stated power levels, while time-to-event outputs use a total event count.

These assumptions are hypothetical planning choices and do not turn the single-group study into a two-arm trial. A planning sample size is not observed power, and it does not establish that the completed study had a particular probability of detecting an effect. No numerical planning results are included in the registry entries for interpretation. In addition, the primary endpoint estimate that might anchor an observed-effect illustration is not reported in the registry record. The planning assumptions therefore cannot replace the missing endpoint result or serve as evidence about the regimen’s observed safety.

More generally, a sample-size calculation depends on the outcome scale, the effect considered important to detect, the expected variability or event frequency, the analysis method, and the chosen error and power criteria. Those inputs are not all reported as trial design choices in this record. The planning illustration assumptions should not be mistaken for a documented protocol calculation or evidence of the study’s original rationale.

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("Group 1")
n      <- c(30)
events <- c(13)
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  Group 1  30  13  43.3  25.5  62.6  27.4  60.8  27.3  60.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the proportion of patients experiencing grade 3 or 4 diarrhea. It does not report an analysis of that endpoint. The existence of a single listed outcome does not establish that there were no additional analyses or outcomes in the full study; a multiplicity strategy is not reported in the registry record.

Multiplicity arises when several outcomes, comparisons, time points, or subgroup analyses are examined. Testing many questions can increase the chance of at least one apparently notable result by chance. Statistical plans may address this through prespecified outcome hierarchies or adjustment procedures. The record does not report whether such procedures were planned or used, so the handling of multiplicity cannot be assessed.

The endpoint population is described as all evaluable patients. The registry does not give the evaluable count, define evaluability, report missing endpoint observations, or state how missing data were handled. It is therefore not possible to determine whether every enrolled participant contributed to the primary endpoint, or whether exclusions or incomplete follow-up affected the result.

For a safety endpoint, follow-up and event ascertainment matter: participants need an opportunity for events to be observed, and the analysis needs a clear rule for classifying events and handling incomplete observation. The timeframe is listed as up to 10 years, but details of assessment schedules, censoring, missingness, or follow-up completeness are not reported in the registry record.

These omissions do not show that the study lacked a statistical plan or that data were missing. They mean the registry record does not contain enough information to assess those issues. Without the primary result, analysis population details, and missing-data methods, readers cannot evaluate the robustness of the endpoint estimate.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (23.3%), platelet count decreased (10.0%), hemoglobin decreased (6.7%), nausea (6.7%), bone pain (6.7%).

The registry’s adverse-event summary reports 10 affected participants among 30 at risk for serious adverse events. For other adverse events, it reports 30 affected among 30 at risk. These categories should be read as separate registry summaries; they do not provide the missing result for the primary endpoint of grade 3 or 4 diarrhea.

The serious-event terms are reported as diarrhea, 23.3%; platelet count decreased, 10.0%; hemoglobin decreased, 6.7%; nausea, 6.7%; bone pain, 6.7%; and abdominal pain, 3.3%. These are term-level percentages. The record does not provide the corresponding counts for each term or clarify overlap between people with different terms, so the percentages should not be added together or converted into counts.

Seriousness and severity are different classifications. A serious adverse event is not automatically a grade 3 or 4 event, and the serious-event listing cannot be used to infer the primary endpoint frequency. The death count is not reported in the registry record. The adverse-event summaries describe what is posted; without a comparator, they do not establish that the regimen caused the events or permit a comparative safety estimate.

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

The record establishes that this completed phase II study evaluated a four-drug regimen in a single group of patients with early stage breast cancer. Its listed primary safety question concerns the proportion experiencing grade 3 or 4 diarrhea, measured using NCI CTCAE v3.0. The registry also reports summary counts for serious and other adverse events, along with selected serious-event terms.

The primary endpoint result itself is not reported in the registry record. As a result, the posted information does not show the observed frequency of grade 3 or 4 diarrhea, the precision of that estimate, or how many evaluable patients contributed. No primary endpoint analysis is listed. This is a limit on what can be concluded from the record, not evidence that the endpoint was absent or that no analysis was done elsewhere.

The serious-event and other-event summaries are descriptive. They do not answer the primary endpoint question, and they do not compare this regimen with another option. Since there is no concurrent control group, the study cannot estimate a comparative treatment effect from its design. The event summaries also cannot establish that each reported event was caused by the regimen.

The record does not report tumor-response results or other evidence that would support conclusions about efficacy. The stated purpose is safety-focused, and the listed primary endpoint is an adverse event. No conclusion that the regimen works or does not work follows from these registry entries.

Interpretation should therefore remain limited to the study design and the adverse-event summaries actually posted. A fuller assessment of the primary safety question would require the endpoint numerator and denominator, an analysis method, and information about endpoint ascertainment and missing observations. Those details are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically relevant because it asks a defined safety question about a combination regimen rather than relying only on a broad account of adverse events. Specifying grade 3 or 4 diarrhea under NCI CTCAE v3.0 identifies an event category and severity threshold that can, in principle, be summarized as a participant proportion. The endpoint’s usefulness depends on the result being reported with its analysis population and uncertainty.

The single-group design is important to the interpretation. It can describe events recorded among participants receiving the regimen, but it does not provide a concurrent estimate of what would have occurred under another treatment. That distinction is central when moving from event description to comparative conclusions. The registry’s allocation and masking entries make clear that no randomized, masked comparison is described.

The record also illustrates why outcome labels are not enough on their own. An endpoint name and timeframe do not reveal the event frequency, denominator, precision, or handling of missing information. Here, the primary result and its analysis are not reported, so readers cannot quantify the main safety outcome named by the study. The adverse-event summary contributes information but is not a substitute for that endpoint.

Finally, planning illustrations and observed results answer different statistical questions. Planning assumptions can describe how a hypothetical design might be sized under stated conditions, but they do not establish what happened in this completed single-group study. Keeping those distinctions clear prevents design calculations, event summaries, and primary outcome estimates from being treated as interchangeable evidence.

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 primary limitation for interpreting this trial from the registry record is that the listed primary endpoint has no posted result or analysis. The record does not give the number of evaluable participants, the number experiencing grade 3 or 4 diarrhea, or an uncertainty interval. The enrollment count cannot be assumed to be the endpoint denominator.

The study is single group, unmasked, and has no concurrent comparator. Its safety summaries are therefore descriptive and cannot quantify a comparative difference or establish causation. The registry does not report a statistical plan, adjustment methods, or procedures for event assessment that would clarify how these design features were addressed.

Information about the analysis population and missing data is also limited. Although the endpoint population is described as all evaluable patients, the criteria for evaluability, follow-up completeness, and handling of incomplete observations are not reported. The timeframe is listed as up to 10 years, but the record does not detail the assessment schedule or duration of observation for individual participants.

The serious adverse-event summary provides group-level counts and selected term percentages, but it does not report event-specific counts or clarify overlap between terms. The death count is not reported in the registry record. The regimen description is truncated, limiting what can be said about treatment discontinuation details. These limitations concern interpretation of the registry record and do not establish what information may be available elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Docetaxel, Carboplatin, Trastuzumab, and Lapatinib in Treating Patients With Early Stage Breast Cancer — NCT00820872.
• Registry record last updated 2019-10-21; status last verified 2019-10.
• Results first posted 2017-03-22.
• 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

NCT00820872 is a completed phase II, single-group study of docetaxel, carboplatin, trastuzumab, and lapatinib ditosylate in early stage breast cancer. The registry lists enrollment of 30, no masking, and allocation marked not applicable. The study start is listed as 2009-02 and primary completion as 2010-12.

The primary endpoint is the proportion of evaluable patients experiencing grade 3 or 4 diarrhea under NCI CTCAE v3.0, with a timeframe of up to 10 years. The primary outcome result and analysis are not reported in the registry record. The adverse-event summary reports 10 affected among 30 at risk for serious events and 30 affected among 30 at risk for other events. These descriptive summaries do not replace the missing primary endpoint result or provide a comparison with another treatment.