This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate Corrected QT Interval and Drug-Drug Interaction of Trastuzumab on Carboplatin in the Presence of Docetaxel in Patients With HER2-Positive Metastatic or Locally Advanced Inoperable Cancer (NCT00927589), a na phase 1 study. The primary outcome is Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00927589 |
| Phase | Phase 1 |
| Condition | Solid Cancers |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with HER2-positive metastatic or locally advanced inoperable cancer. The registry also lists solid cancers as the condition. The primary endpoint population is described as ECG-evaluable participants: those who received trastuzumab and had interpretable ECG measurements at baseline and at a steady-state assessment. The registry record’s description of the population ends mid-sentence, so further eligibility details are not reported in the registry record.
Intervention
Participants received trastuzumab, docetaxel, and carboplatin. The study was open-label, and the intervention is described as a single group rather than as randomized treatment arms.
Comparator
There was no concurrent comparison group. Allocation is listed as not applicable, and the registry describes a single-group study. Therefore, the design does not provide a like-for-like control group for comparing QT interval changes or other outcomes.
Primary question
The primary endpoint asks for the mean change from baseline in Fridericia-corrected QT interval (QTcF) at trastuzumab steady state. ECG measurements were planned at baseline, Cycle 1 Day 8, and Cycle 2 Day 1. The study’s description also identifies the evaluation of trastuzumab’s effect on QTcF and its effects on carboplatin pharmacokinetics. Numerical primary endpoint results are not reported in the registry record.
3. Trial Design
This is a Phase 1b, multicenter, single-arm, open-label clinical trial. The registry lists an enrollment of 59 and a completed status. The recorded study start is 2009-07, and primary completion is recorded as 2013-02. The sponsor is Genentech, Inc. No random allocation or masking is described; allocation is listed as not applicable and masking as none.
The treatment group is described as trastuzumab plus docetaxel plus carboplatin. Participants were assessed for changes in corrected QT interval and for the effects of trastuzumab on carboplatin pharmacokinetics. The stated primary endpoint focuses on mean change in QTcF at trastuzumab steady state, defined as the average of ECG measurements collected on Cycle 1 Day 8 and Cycle 2 Day 1 after the trastuzumab infusion.
For the primary endpoint, ECG recordings were triplicate 12-lead measurements, with each recording separated by approximately 2 minutes. The average was calculated, and QT was corrected for the RR interval using Fridericia’s formula. The stated assessment times include baseline, Cycle 1 Day 8, and Cycle 2 Day 1. The registry lists additional ECG-related secondary outcomes, including QTcB, PR interval, QRS duration, heart rate, QT interval categories, and ECG waveform abnormalities.
A single-group design can describe changes observed during treatment, but without a concurrent comparison group it cannot isolate treatment-related changes from other influences or establish how outcomes would have differed under another treatment. Protocol details such as the sample-size justification, planned interim analyses, and full statistical analysis plan are not reported in the registry record.
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
| Stage | Trastuzumab + Docetaxel + Carboplatin |
|---|---|
| STARTED | 59 |
| COMPLETED | 43 |
| NOT COMPLETED | 16 |
Reasons for not completing this period:
| Reason | Trastuzumab + Docetaxel + Carboplatin |
|---|---|
| Death | 1 |
| Physician Decision | 1 |
| Withdrawal by Subject | 3 |
| Adverse Event | 2 |
| Disease Progression | 8 |
| Non-compliance | 1 |
Analysis population for the primary outcome, as defined in the registry: ECG-evaluable participant population: received any trastuzumab, had at least 1 interpretable baseline ECG measurement recorded on C1D2 prior trastuzumab exposure, had at least 1 interpretable ECG measurement recorded on C1D8 or C2D1 corresponding to time of steady-state trastuzumab concentration, and no infusion reaction requiring drug treatments.
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: All enrolled participants
| Characteristic | Unit | Trastuzumab + Docetaxel + Carboplatin |
|---|---|---|
| Participants analysed | 59 | |
| Age, Continuous | years | 59.0 (SD 12.1) |
| Sex: Female, Male: Female | Participants | 33 |
| Sex: Female, Male: Male | Participants | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State, measured over Baseline, Cycle 1 Day 8 and Cycle 2 Day 1.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 90% Confidence Interval |
| Unit | milliseconds (msec) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is mean change from baseline in QTcF, measured in milliseconds. The QT interval represents the time from the start of ventricular depolarization to the end of ventricular repolarization on an ECG. Because the QT interval varies with heart rate, it is adjusted for the RR interval, the interval between heartbeats. The study specifies Fridericia’s correction: QT divided by the cube root of RR.
Correction is used to make QT measurements more comparable when heart rates differ. The endpoint focuses on change from baseline rather than only the measured QTcF at follow-up, so it describes how the average corrected interval differs from the participant’s baseline measurement. The endpoint uses ECG-evaluable participants who had trastuzumab exposure and interpretable ECG measurements at baseline and at a steady-state time point, according to the registry description.
Steady state is defined in the record using the average of measurements on Cycle 1 Day 8 and Cycle 2 Day 1 after trastuzumab infusion. Repeated ECG recordings were averaged as described in the protocol summary. The registry specifies a 90% confidence interval as the measure of dispersion for the mean. However, the mean change and its confidence interval are not reported in the registry record, so the magnitude and precision of the primary endpoint cannot be assessed from the recorded information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a study designed to examine QTcF change during treatment with trastuzumab, docetaxel, and carboplatin, and to characterize trastuzumab’s effects on carboplatin pharmacokinetics. It identifies a primary ECG endpoint and several secondary ECG outcomes. It does not report numerical results for the primary endpoint in the record summarized for this analysis. Accordingly, neither the direction nor the size of the mean QTcF change can be described, and its statistical precision cannot be evaluated.
A confidence interval would ordinarily show the range of values compatible with the observed data under the analysis assumptions. Its width conveys precision: a narrower interval generally indicates a more precise estimate, while a wider interval indicates greater uncertainty. The registry specifies a 90% confidence interval for the primary endpoint, but its limits are not reported in the registry record. No conclusion about the estimated QTcF change or the uncertainty around it can therefore be drawn from that specification alone.
The design is single-arm and open-label, with no randomized comparator. Any observed before-and-after change would be a description of the study group over time, not a controlled estimate of what the treatment caused. Changes might also reflect factors other than treatment, including time-related changes or measurement variability. The design therefore limits causal interpretation even if numerical outcomes were available.
The registry records an enrollment of 59, while the primary endpoint population is defined by ECG evaluability and treatment exposure. The number of participants included in that endpoint analysis is not reported in the registry record. Enrollment and an analysis population are not interchangeable: participants may not all have the measurements required for a particular outcome.
The registry lists 20 outcome measures and zero analyses. This does not provide a statistical analysis plan or numerical results. The planned secondary outcomes include QTcB change, baseline-adjusted ECG intervals and heart rate, and counts of participants within QTc categories or with ECG changes. Their results are not reported in the registry record. The listed safety information includes serious and other adverse-event figures, but these are descriptive reports and do not establish comparative risks in the absence of a control group.
The record gives assumptions for planning illustrations, including a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of an observed effect. Those assumptions describe planning calculations, not an observed power analysis for this single-arm trial. No numerical planning results or observed primary effect are reported in the registry record, so the illustrations cannot be evaluated as evidence about the study’s findings.
9. Statistical Methods Explained
The primary endpoint is a mean change, a summary of the average difference between baseline and the specified follow-up assessment for the ECG-evaluable participants. A mean can be useful when the clinical question concerns the average shift in a continuous measurement. It does not, by itself, describe how individual participants’ measurements were distributed. The registry record does not report the primary endpoint mean, the number of participants analyzed, or the confidence interval limits.
Why correct QT for heart rate?
The QT interval varies with heart rate, so a raw interval can be difficult to compare across ECGs recorded at different rates. The study uses Fridericia’s correction, which adjusts QT using RR. The registry also lists secondary outcomes using Bazett’s correction. These are distinct correction methods; the registry does not report numerical results that would allow their estimates to be compared. In general, a correction formula is a statistical adjustment, not a direct measurement of a separate physiological process. The adjusted result depends in part on the formula used.
The protocol description states that triplicate 12-lead ECG recordings were made, with each recording separated by approximately 2 minutes, and an average was calculated. Repeated readings can help represent the measurement at an assessment time while reducing the influence of a single reading. Averaging does not remove all measurement error or biological variation. The registry does not provide the variability among repeated readings or details of how incomplete recordings were handled.
What does a confidence interval convey?
The primary endpoint specifies a 90% confidence interval around the mean. In general, a confidence interval expresses uncertainty about an estimated quantity under the statistical model and analysis procedure. It is not a guarantee that the true value falls within a particular interval, and it is not a description of the range of individual participant responses. A reported interval would need to be interpreted together with the point estimate and the analysis population. Neither the point estimate nor the limits are reported in the registry record.
The confidence level alone does not show whether the estimate is precise. Precision depends on the observed data and analysis, including the amount of variation and the number of observations contributing to the estimate. The number enrolled is listed as 59, but the count contributing to the primary analysis is not reported in the registry record. It would therefore be inappropriate to infer the endpoint’s precision from enrollment alone.
How should a single-group change be understood?
In a single-group study, a before-and-after estimate describes change over time among participants who meet the analysis criteria. Without a concurrent comparison group, the estimate cannot separate a treatment-associated change from changes that might have occurred for other reasons. This limitation applies even when the measurement is objective and collected using a stated procedure. Open-label status means masking is not used, as recorded in the registry; the record does not describe further procedures to limit measurement or analysis bias.
The primary endpoint population is defined in part by receipt of trastuzumab and interpretable ECG measurements at baseline and at a steady-state assessment. This eligibility definition can make the analyzed group differ from everyone enrolled. The registry description of the population is incomplete, and the number meeting the criteria is not reported in the registry record. The record also does not report how missing or uninterpretable ECG measurements were handled.
What do the planning assumptions mean?
In general, power calculations estimate how often a statistical procedure would detect an effect of a specified size under stated assumptions. The planning assumptions recorded for the illustrations refer to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of the observed effect. These are planning assumptions and do not show the probability that this completed study detected an effect. They should not be read as observed power.
The record’s planning description refers to two arms, whereas the clinical trial itself is recorded as single-group. Such planning illustrations are hypothetical design calculations rather than a description of the study’s allocation. The numerical planning results and the observed effect used for those calculations are not reported in the registry record. The trial’s own sample-size justification is also not reported in the registry record.
What about multiple outcomes?
The registry lists multiple ECG outcomes, including different QT corrections, other ECG intervals, heart rate, and counts of ECG findings. In general, examining multiple outcomes or multiple statistical tests can increase the chance of at least one apparently notable result arising by chance. A prespecified testing strategy or adjustment can address some multiplicity concerns, but the registry does not report a multiplicity procedure or a complete statistical analysis plan. The record’s listing of outcome measures does not establish which tests, if any, were formally conducted.
The registry reports zero analyses. Thus, it does not supply estimates, test statistics, or p-values for the listed endpoints. Recalculation from summary statistics is not possible when the relevant numerical summaries are absent. Any numerical conclusion about an endpoint would require results not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, including a primary QTcF endpoint and secondary ECG outcomes such as QTcB change, baseline-adjusted PR and QRS intervals, heart rate, QT categories, and ECG waveform findings. It records zero analyses. A full account of which outcomes were tested, the order of testing, or whether any multiplicity adjustment was planned is not reported in the registry record. In general, when many outcomes are examined, the chance of at least one result appearing notable by chance can increase. The record does not establish that any particular adjustment was used.
The primary endpoint population is defined by trastuzumab exposure and interpretable ECG measurements at baseline and at a steady-state assessment. The record does not report the number of participants included in the primary endpoint analysis or describe how missing, uninterpretable, or incomplete ECG data were handled. It does not state whether any imputation, exclusion rule, or sensitivity analysis was used. These details are important because the analysis population and missing-data approach can affect the interpretation of an estimate.
The registry’s population description ends mid-sentence, so additional eligibility or analysis-population details are not reported in the registry record. A protocol-level statistical analysis plan, the sample-size justification, and interim-analysis procedures are also not reported in the registry record. The listed enrollment of 59 does not establish how many participants contributed to each outcome.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Trastuzumab + Docetaxel + Carboplatin | 26 | 58 | 44.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Trastuzumab + Docetaxel + Carboplatin | 56 of 58 |
Most frequent serious adverse event terms
| Event term | Organ system | Trastuzumab + Docetaxel + Carboplatin |
|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 5 of 58 |
| Small intestinal obstruction | Gastrointestinal disorders | 3 of 58 |
| Pneumonia | Infections and infestations | 3 of 58 |
| Colitis | Gastrointestinal disorders | 2 of 58 |
| Dehydration | Metabolism and nutrition disorders | 2 of 58 |
| Constipation | Gastrointestinal disorders | 1 of 58 |
| Diarrhoea | Gastrointestinal disorders | 1 of 58 |
| Diverticular perforation | Gastrointestinal disorders | 1 of 58 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 58 |
| Haematemesis | Gastrointestinal disorders | 1 of 58 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Trastuzumab + Docetaxel + Carboplatin |
|---|---|---|
| Neutrophil count decreased | Investigations | 37 of 58 |
| Nausea | Gastrointestinal disorders | 34 of 58 |
| Haemoglobin decreased | Investigations | 33 of 58 |
| Fatigue | General disorders | 31 of 58 |
| Diarrhoea | Gastrointestinal disorders | 30 of 58 |
| Platelet count decreased | Investigations | 23 of 58 |
| Vomiting | Gastrointestinal disorders | 22 of 58 |
| Alopecia | Skin and subcutaneous tissue disorders | 18 of 58 |
| Decreased appetite | Metabolism and nutrition disorders | 17 of 58 |
| White blood cell count decreased | Investigations | 16 of 58 |
Serious events with the highest arm-level rate: febrile neutropenia (8.6%), small intestinal obstruction (5.2%), pneumonia (5.2%), colitis (3.4%), dehydration (3.4%).
The registry lists one treatment group, titled trastuzumab plus docetaxel plus carboplatin. Serious adverse events are recorded for 58 participants at risk, with 26 participants affected. Other adverse events are recorded for 58 participants at risk, with 56 participants affected. These are descriptive figures for the study group; there is no concurrent control group for a like-for-like safety comparison.
The most frequently listed serious adverse-event terms are febrile neutropenia at 8.6%, small intestinal obstruction at 5.2%, pneumonia at 5.2%, colitis at 3.4%, dehydration at 3.4%, and constipation at 1.7%. The registry record does not give additional detail in these figures about severity grades, timing, duration, or whether each event was judged related to a particular drug. The death figure is not reported in the registry record.
Adverse-event figures describe events recorded during the study and should not be treated as proof of cause. Because the design has no comparison group, these data cannot establish how event frequency compares with another treatment or with what would have occurred without the regimen.
12. What the Result Does, and Does Not, Mean
The registry identifies the clinical question and the measurement approach: mean change from baseline in Fridericia-corrected QT interval at trastuzumab steady state, assessed using ECGs at the stated study times. It also describes the regimen and lists secondary ECG outcomes and adverse-event information. These details explain what the trial was designed to assess, but they are not a report of the primary endpoint’s numerical outcome.
Without the primary mean change, its 90% confidence interval, and the number of participants analyzed, the size and precision of any observed QTcF change cannot be evaluated. The record also does not report numerical results for the secondary ECG outcomes or the stated carboplatin pharmacokinetic objective. No conclusion about the direction, magnitude, or statistical uncertainty of those outcomes can be drawn from the registry information.
Even if a numerical before-and-after change were available, the single-arm design would limit causal interpretation. It would describe a change in the analyzed group over time, without showing what would have happened under a concurrent alternative. The open-label design and the ECG-evaluable population are also relevant when considering how the study was conducted and which participants contribute to an endpoint.
The safety figures document adverse events among participants in the treatment group, including the listed serious-event terms. They do not provide a comparative estimate of safety, and the registry record does not report whether individual events were attributed to a specific study drug. The figures should therefore be read as descriptive study information rather than as evidence of a causal or comparative effect.
Overall, the record supports a description of the study design, endpoint definitions, and selected safety counts. It does not report the outcome estimates needed to judge the observed QTcF change or its precision. A missing result is not evidence that no change occurred; it means that the result is not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between defining an endpoint and reporting its result. The registry specifies a continuous primary outcome, describes how QT is corrected for heart rate, identifies the ECG assessment times, and states that a 90% confidence interval was intended to accompany the mean change. Those details make the measurement question explicit. Without the estimate and interval, however, readers cannot assess the magnitude or precision of the change.
It also highlights why the analysis population matters. The primary endpoint applies to participants with the required exposure and interpretable ECG measurements, rather than automatically to everyone enrolled. The enrollment figure alone does not reveal how many contributed to the endpoint or whether missing ECG data could affect the estimate. Transparent reporting of the analyzed population and missing-data handling is important for interpreting continuous outcomes.
The single-arm, open-label design makes the study suitable for describing observations within the treatment group, but it does not offer a randomized comparison. Statistical estimates from such a design should not be mistaken for controlled treatment effects. A clear distinction between observed change and causal attribution is essential when interpreting early-phase research.
Finally, the registry’s many listed outcomes make multiplicity and reporting choices relevant. The record does not describe a complete statistical plan or multiplicity procedure, and it records zero analyses. This means the outcome list cannot be used to infer which statistical tests were completed or how their results were handled. The study is therefore a useful example of how design, endpoint specification, analysis-population reporting, and complete numerical results all contribute to statistical interpretability.
14. 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 interpreting the primary endpoint is that its numerical result is not reported in the registry record. The mean change, 90% confidence interval limits, and number analyzed are unavailable, so neither the observed magnitude nor its precision can be assessed. The registry also records zero analyses, and numerical results for the listed secondary outcomes are not reported in the registry record.
The single-group, open-label design has no concurrent control. Any observed change would not, by itself, separate treatment-associated effects from other changes over time or measurement variation. The record describes a defined ECG procedure, including triplicate recordings, but does not report the variation among repeated recordings or additional measures used to address potential bias.
The primary endpoint population depends on trastuzumab exposure and interpretable ECG measurements at specified times. The registry description of that population is incomplete, and the number of participants who met the criteria is not reported in the registry record. The approach to missing or uninterpretable ECG data is also not reported in the registry record, leaving uncertainty about how the analysis population was formed.
The record lists multiple ECG and safety outcomes but does not report a full statistical analysis plan, a multiplicity strategy, an interim-analysis plan, or the trial’s sample-size justification. Although planning assumptions are described for hypothetical two-arm calculations, numerical planning results and the observed effect used for them are not reported in the registry record. The planning illustrations should not be interpreted as observed power or as the trial’s own design justification.
Safety information is descriptive for one treatment group. The record does not report deaths, and it does not provide additional detail about event timing, severity, or attribution to individual drugs in the figures summarized. Without a comparison group, these counts do not establish comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Corrected QT Interval and Drug-Drug Interaction of Trastuzumab on Carboplatin in the Presence of Docetaxel in Patients With HER2-Positive Metastatic or Locally Advanced Inoperable Cancer — NCT00927589.
- Registry record last updated 2015-12-10; status last verified 2015-11.
- Results first posted 2015-12-10.
- 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.
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18. Record Summary
NCT00927589 is a completed Phase 1b, multicenter, single-arm, open-label study of trastuzumab, docetaxel, and carboplatin in patients with HER2-positive metastatic or locally advanced inoperable cancer. The registry records enrollment of 59, a start of 2009-07, and primary completion in 2013-02.
The primary endpoint is mean change from baseline in QTcF at trastuzumab steady state, with a 90% confidence interval specified. The record also describes secondary ECG outcomes and an objective to characterize trastuzumab’s effects on carboplatin pharmacokinetics. Numerical primary and secondary outcome results are not reported in the registry record.
The safety record lists adverse-event figures for a treatment group with 58 participants at risk and gives selected serious adverse-event terms. The single-group design does not provide a concurrent comparator, and protocol details such as the sample-size justification, interim analyses, full statistical plan, and missing-data methods are not reported in the registry record.