Study Of SU011248 In Combination With Docetaxel In Patients With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of SU011248 In Combination With Docetaxel In Patients With Metastatic Breast Cancer (NCT00291577), a non-randomized phase 1 study. The primary outcome is Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters.

2. Clinical Question

The stated purpose was to evaluate the safety of combining sunitinib with docetaxel in participants with metastatic or locally recurrent breast cancer who had not received chemotherapy for advanced disease. The primary endpoint is pharmacokinetic rather than a direct measure of tumor response or disease progression. It concerns the timing of peak plasma concentrations for sunitinib, the sunitinib metabolite SU012662, and the combined total drug.

The record also lists progression-free survival, objective response, clinical benefit, and duration of tumor response as secondary outcomes. Those outcomes address different questions from the primary pharmacokinetic endpoint: they concern disease course or tumor response rather than drug concentration over time. Numerical results for those secondary outcomes are not reported in the registry record.

Because all participants were in a single group and there was no randomized comparator, the study can describe observations made during the combination regimen but cannot establish a comparative effect against another treatment. The registry record reports 22 enrolled participants. It does not give numerical primary-endpoint estimates in the record, so the question is defined but its estimated answer cannot be read from the record.

3. Trial Design

This was a phase 1 study with a non-randomized allocation and a single-group model. Masking was listed as none. The registry record lists 22 participants as enrolled and the study status as completed. It identifies Pfizer as the sponsor. The record gives the study start as 2006-07 and primary completion as 2008-10.

The single group received sunitinib in combination with docetaxel. There was no separately assigned control arm, and the arm description field contains no further description. Consequently, the design is suited to recording outcomes and pharmacokinetic observations in the treated group, not to estimating a randomized between-group treatment contrast. Differences from another population, regimen, or study cannot be interpreted as controlled comparisons based on this design.

The primary outcome is time to reach maximum plasma concentration, or Tmax, for sunitinib, its metabolite SU012662, and total drug. The registry describes the endpoint using the median and full range, with sampling at 1, 2, 4, 6, 8, 12, and 24 hours postdose. It identifies paired observations collected at C1D2 and C2D3. These details describe the planned measurement; the numerical Tmax summaries are not reported in the registry record.

The pharmacokinetic evaluable set is defined as participants in the ITT population who completed sampling for pharmacokinetic profiles for both sunitinib and docetaxel. The ITT population is defined as all enrolled participants who received at least one dose of either study medication. These definitions distinguish the population used for the pharmacokinetic endpoint from the broader treated population, but the sizes of those populations are not reported in the registry record.

The record lists 16 outcome measures and 13 analyses. These counts do not, by themselves, reveal which analyses were prespecified, how they were selected, or how any multiplicity was handled. Those details 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.

Before assignment: First 12 subjects evaluable for pharmacokinetic (PK) analysis had full PK profile on Cycle 1, Day 1 (C1D1) and C2D1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable set of subjects for PK analysis is subjects in ITT population who completed sampling for PK profiles for both SU011248 and docetaxel; ITT population = all subjects enrolled in study who received at least 1 dose of study medication (SU011248 or docetaxel).

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 Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters, measured over 1, 2, 4, 6, 8, 12, 24 hours postdose.

The primary endpoint is Tmax, the time taken to reach the maximum plasma concentration, for sunitinib, the metabolite SU012662, and their combined total drug. The registry describes results in terms of the median and full range. It specifies postdose sampling at 1, 2, 4, 6, 8, 12, and 24 hours, with paired observations collected at C1D2 and C2D3. Numerical endpoint estimates and ranges are not reported in the registry record.

As a general pharmacokinetic concept, Tmax characterizes the timing of peak measured drug concentration. It is different from the peak concentration itself, the total exposure over time, and a clinical outcome such as tumor response. The time at which a peak is observed can help describe a concentration profile, but Tmax alone does not establish whether a regimen changes disease outcomes or whether one treatment is better than another.

Using the median gives a measure of the center of the observed Tmax values that is less influenced by unusually high or low observations than the arithmetic mean. The full range describes the span from the lowest to the highest observed value, but it does not show how observations are distributed between those endpoints. With no numerical median or range posted in the registry record, readers cannot assess the observed timing or its variability from this record.

The endpoint is used as a pharmacokinetic description of the combination regimen. It does not answer the safety question on its own. Safety is addressed through adverse-event reporting, while progression-free survival and tumor-response outcomes are listed separately as secondary outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is sufficient to identify the study structure and the form of the primary endpoint, but not to reconstruct a complete analysis. The study is a single-group, non-randomized phase 1 study. Its primary pharmacokinetic outcome is summarized using a median and full range. Numerical endpoint values, confidence intervals, and detailed methods for the listed secondary outcomes are not reported in the registry record.

What does the median describe?

As a general statistical concept, the median is the central value when observations are ordered. It is often useful for measurements that may be asymmetric or have unusually extreme observations, because extreme values do not pull it in the same way they can pull an arithmetic mean. In this study, the median is specified for Tmax. Without the posted median and the number of observations contributing to it, the central observed timing cannot be evaluated from the registry record.

The full range reports the lowest and highest observed values. It makes the endpoints of the observed spread visible, but it does not show how densely observations cluster, whether there are gaps, or whether most values lie near one end. A range can also be sensitive to extreme observations. General statistical interpretation is stronger when a suitable measure of spread and the underlying sample size are available together. The registry record does not give numerical Tmax ranges or the size of the pharmacokinetic evaluable set.

What do the sampling details mean?

The endpoint description identifies measurements after dosing at 1, 2, 4, 6, 8, 12, and 24 hours. In general, sampling times define when concentration measurements are collected and can affect how well a peak is captured. A peak occurring between sampling times may not be directly observed; the precision of a Tmax estimate depends on the sampling schedule and the analysis approach. The registry record specifies the schedule but does not report the concentration profiles or further details of how Tmax was derived.

The record describes paired observations collected at C1D2 and C2D3. In general, paired observations are linked measurements from the same participant or matched observational unit, rather than unrelated measurements from separate groups. Pairing can be useful when the analysis concerns within-participant changes or repeated measurements. The record does not report a numerical paired comparison or a detailed model for those observations, so no such result can be inferred from the endpoint description alone.

How should a confidence interval be read?

As a general explanation, a confidence interval expresses uncertainty around an estimate under a specified statistical procedure. It is not a guarantee that the true value lies within a particular interval. Its width reflects precision: wider intervals indicate more uncertainty than narrower intervals, all else equal. An estimate and its interval together are generally more informative than a significance label alone. No confidence interval for the primary endpoint or the listed tumor-related outcomes is reported in the registry record.

For event outcomes, the observed count and the number of participants at risk give basic context. A comparative effect estimate would require a defined contrast and an appropriate analysis. This study has no randomized comparator group, so its single-group safety counts do not provide a randomized estimate of relative risk. The record also does not report adjusted estimates or uncertainty intervals for those counts.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability in count data exceeds what a chosen model assumes. If a model assumes less variability than the data contain, standard errors can be too small and uncertainty can appear understated. Methods that account for extra variability may be appropriate for some count outcomes. However, the registry record does not report a count model or indicate whether over-dispersion was assessed. This general issue should not be read as evidence that over-dispersion occurred in this study.

The record identifies 16 outcome measures and 13 analyses, but these totals do not specify the statistical tests, models, covariates, or decision rules. The analysis methods for the secondary outcomes, handling of censoring for progression-free survival, and any approach to repeated measurements are not reported in the registry record. It is not appropriate to infer those methods from the outcome names.

Planning sample sizes, when based on an observed effect and stated assumptions, are illustrations of how a future study might be planned. They are not observed power and do not measure the probability that this completed study found a true effect. The stated planning assumptions describe 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 fraction of the observed effect. Those assumptions do not match this study's single-group design as a direct trial comparison. Numerical planning outputs and the study's own sample-size justification are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 16 outcome measures and 13 analyses. Multiple outcomes and analyses can create multiplicity: when many statistical questions are considered, the chance of at least one apparently notable result can increase if each is judged separately. As a general principle, interpretation depends on which outcomes and analyses were prespecified, how they were prioritized, and whether any adjustment or other multiplicity strategy was used. Those details are not reported in the registry record. The counts alone do not establish that a particular adjustment was or was not performed.

The record identifies Tmax as the primary endpoint and lists progression-free survival, objective response, clinical benefit, and duration of tumor response among secondary outcomes. It does not provide numerical results for these endpoints in the record, nor does it explain how multiple endpoint analyses were interpreted. A hierarchy of endpoints, testing procedure, or plan for handling repeated analyses is not reported in the registry record.

The analysis populations are defined in general terms. The ITT population includes enrolled participants who received at least one dose of sunitinib or docetaxel. The pharmacokinetic evaluable set is drawn from that population and requires completed sampling for pharmacokinetic profiles for both drugs. The numbers included in each population and the reasons for any exclusions or missing samples are not reported in the registry record.

The registry record does not describe how missing data were handled for pharmacokinetic measurements, progression-free survival, or tumor-response outcomes. It also does not state whether sensitivity analyses were performed. Missing-data methods can affect estimates when the availability of measurements is related to participant characteristics or outcomes; this is a general concern, not a finding about this study. Without the analysis details and results, the impact of missing data cannot be assessed.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (18.2%), neutropenia (9.1%), leukopenia (4.5%), stomatitis (4.5%), fatigue (4.5%).

The registry record lists 22 participants at risk for serious adverse events and 11 affected. For other adverse events, it lists 22 at risk and 21 affected. These are counts in the study group, not comparisons with another regimen. The record does not report a deaths value.

The listed serious adverse-event terms are febrile neutropenia at 18.2%, neutropenia at 9.1%, and leukopenia, stomatitis, fatigue, and oedema peripheral each at 4.5%. These percentages describe the terms as recorded; they do not show duration, severity beyond the serious-event classification, timing, management, or whether an individual experienced more than one listed event. The registry record does not provide that additional detail.

Serious adverse events and other adverse events are separate reporting categories in the record. The counts should not be added together: a participant may have contributed to more than one category, and the record does not specify the overlap. In general, adverse-event counts describe what was reported during a study and do not by themselves establish that a study drug caused an event. With no comparator group, these figures also cannot quantify a comparative safety difference.

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

The record establishes that a phase 1 study evaluated sunitinib in combination with docetaxel in a single group of participants with advanced breast cancer. It defines a primary pharmacokinetic endpoint and reports selected safety figures. It does not report numerical results for the primary endpoint or the listed secondary tumor-related outcomes in the record. As a result, the study's observed Tmax values, progression-free survival estimates, and tumor-response results cannot be described from this record.

The safety figures show that 11 of 22 participants were listed as affected by serious adverse events and 21 of 22 were listed as affected by other adverse events. Selected serious-event terms are reported with percentages. These are descriptive observations among participants in this study; they do not establish causation or compare the regimen with an alternative. The deaths value is not reported in the registry record.

The study's single-group design is central to what can be concluded. Without a randomized comparison group, outcomes observed during the study cannot be attributed to the combination through a controlled treatment contrast. The record therefore does not support a causal claim about comparative effectiveness or comparative safety. This limitation remains even when an outcome is clearly defined or a count is available.

General statistical interpretation distinguishes an estimate from its precision and from its clinical meaning. A numerical estimate with an uncertainty interval can show both the direction and plausible range of an association under the analysis assumptions. The registry record does not report such estimates or intervals for the primary and listed tumor-related outcomes. Neither the absence of posted numerical results nor the study's completion status establishes whether a treatment effect was present.

The stated planning illustrations, if consulted, should be understood as design calculations based on an observed effect and specified assumptions. They are not observed power and do not demonstrate that the study was adequately powered for a particular outcome. The registry record does not report the study's own sample-size justification. Overall, the record supports a description of the design, endpoint definitions, and posted safety counts, while leaving the numerical pharmacokinetic and tumor-outcome findings unavailable.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is pharmacokinetic, while several listed secondary outcomes concern tumor response or disease progression. Those endpoint types answer different questions. Tmax describes the timing of a peak plasma concentration; progression-free survival and response outcomes describe clinical events or tumor status. A pharmacokinetic endpoint cannot stand in for a tumor outcome, and the outcome names alone do not provide results.

The single-group design also illustrates the difference between describing an outcome and estimating a comparative treatment effect. Counts and measurements can characterize what was recorded among participants receiving the combination. A randomized control group is not present, so the design does not provide a randomized estimate of how outcomes differ from another treatment or from no study treatment.

The registry definitions of the ITT and pharmacokinetic evaluable populations show why analysis populations matter. The ITT definition requires receipt of at least one dose, while pharmacokinetic evaluation additionally requires completed sampling for both study drugs. In general, results can differ across populations if inclusion depends on treatment exposure or availability of measurements. The population sizes and any missing-data handling are not reported in the registry record, limiting assessment of that issue.

The record also highlights that outcome definitions and analysis details are not interchangeable. Naming 16 outcome measures and 13 analyses does not explain the statistical models, multiplicity strategy, or uncertainty around estimates. Those details are not reported in the registry record. A complete statistical interpretation needs results and methods together, not endpoint labels alone.

Finally, planning calculations must be separated from evidence observed in the completed study. Sample-size illustrations based on observed effects are for planning, not observed power. They cannot supply missing primary or secondary results, and they do not provide a substitute for the study's own design justification, which is not reported in the registry record.

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 most direct limitation for interpretation is that numerical results for the primary pharmacokinetic endpoint are not reported in the registry record. The endpoint is defined by measure, summary, sampling schedule, and collection occasions, but no median or full range is available. The record also does not report numerical results for the listed secondary outcomes concerning progression-free survival and tumor response.

The study has one non-randomized group and no comparator. As a result, posted observations cannot support a controlled estimate of the difference between the combination and another regimen. This design limitation applies to both efficacy interpretation and comparative safety interpretation, regardless of the number of outcome measures listed.

The registry record reports 22 enrolled participants and provides safety counts with 22 listed at risk, but does not report the sizes of the ITT and pharmacokinetic evaluable populations. It does not describe missingness, reasons for incomplete pharmacokinetic sampling, or methods used to handle missing data. The effect of exclusions or unavailable measurements therefore cannot be assessed.

Other methodological details are also not reported in the registry record: the sample-size justification, a complete statistical analysis plan, the models and tests used for secondary outcomes, confidence intervals, and any multiplicity strategy. The counts of outcome measures and analyses do not resolve these gaps. These limitations constrain assessment of precision, analytic choices, and the consistency between planned and reported analyses.

The serious adverse-event information is descriptive. The record gives selected terms and percentages but does not supply additional detail about timing, duration, participant-level overlap, or attribution. The deaths field has no reported value. These absences should not be interpreted as evidence that no events occurred; the corresponding details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Of SU011248 In Combination With Docetaxel In Patients With Metastatic Breast Cancer — NCT00291577.
• Registry record last updated 2009-12-23; status last verified 2009-11.
• Results first posted 2009-12-23.
• 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.

18. Record Summary

NCT00291577 is a completed phase 1, non-randomized, single-group study of sunitinib with docetaxel in women with advanced breast cancer. The registry lists 22 enrolled participants, no masking, and Pfizer as sponsor. The primary endpoint is Tmax for sunitinib, SU012662, and total drug, summarized by median and full range using the stated postdose sampling schedule.

The record defines the ITT and pharmacokinetic evaluable populations and lists secondary outcomes for progression-free survival and tumor response. Numerical results for those outcomes and the primary endpoint are not reported in the registry record. Safety information lists 11 of 22 participants with serious adverse events and 21 of 22 with other adverse events, along with selected serious-event terms and percentages. No randomized comparator is present, and the deaths value is not reported.