Brain Mets - Capecitabine Plus Sunitinib and WBRT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brain Mets - Capecitabine Plus Sunitinib and WBRT (NCT00570908), a na phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

This clinical question concerns the course of disease after a treatment sequence rather than a direct comparison between alternative regimens. The endpoint definition includes progression in either the CNS or outside the CNS, as well as death, so the outcome is broader than control of brain metastases alone. That definition is important when interpreting the measure: a progression event at an extra-CNS site can count even if CNS progression has not been documented.

The study is recorded as phase 2 and single group, with 12 enrolled. Its stated purpose included both efficacy and safety, but the registry record gives no comparative efficacy estimate. It also does not report the primary endpoint's observed median or confidence interval. Therefore, the clinical question can be described from the intended regimen and endpoint, but the posted record does not establish how the endpoint turned out or how precisely it was estimated.

3. Trial Design

The registry describes a phase 2, single-group study with 12 enrolled. Allocation is listed as not applicable, and masking is listed as none. The single study group received capecitabine concurrently with whole brain radiotherapy, followed by capecitabine and sunitinib. The listed interventions include both drugs and radiation. There is no like-for-like control arm in the record, so the design is not a randomized comparison.

The study is titled “Brain Mets - Capecitabine Plus Sunitinib and WBRT.” Its official title describes capecitabine given with whole brain radiotherapy, followed by capecitabine and sunitinib, for CNS metastases in breast cancer. The registry lists the condition as breast cancer and the sponsor as Baylor Breast Care Center. The recorded start is 2009-02, primary completion is 2013-09, and status is terminated. The reason for termination is not reported in the registry record.

The primary outcome is progression-free survival, with a stated timeframe of 2 years. The record defines the interval as beginning at initiation of whole brain radiotherapy with capecitabine and ending at the first documented progression at any site or death from any cause. It identifies five patients as having progressed during study treatment. It also reports that seven patients stopped study treatment early because of an adverse event or withdrawal; six of them were followed for the survival outcome, while one was lost to follow-up after 3.5 months of observation and described as censored.

These design features affect what the results can establish. A single-group study can describe outcomes among people receiving the regimen, but without a concurrent control it cannot isolate the regimen's effect from other explanations for the observed course. The registry record does not report a statistical analysis plan, the reason the study was terminated, or a primary endpoint estimate.

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: 5 patients progressed during the study treatment. 7 patients were off study treatment early due to AE or withdrawal but 6 of them were followed for the survival outcome, 1 was lost to follow up after 3.5 months observation (censored data).

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: 12 patients were enrolled and started treatment

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival, measured over 2 years.

Progression-free survival measures the time from a defined starting point to a specified event. In this trial, the clock begins at initiation of whole brain radiotherapy with capecitabine. The event is the first documented progression at any site or death from any cause. The definition therefore includes CNS and extra-CNS progression rather than restricting the event to brain metastases.

Time-to-event outcomes are useful when the timing of an event matters and participants may have different lengths of observation. A median is a summary of the event-time distribution: it marks the point by which half of the relevant outcome distribution has reached an event, subject to the estimation method and available follow-up. The registry lists the median and a 95% confidence interval as the planned form of the primary outcome, but it does not report the estimate or interval.

The endpoint is clinically interpretable as a measure of time without documented progression or death, but it is not a direct measure of symptom relief, quality of life, or control of CNS disease alone. Because progression at an extra-CNS site qualifies, the endpoint combines disease events across locations. The stated timeframe is 2 years; that timeframe does not, by itself, supply an observed result or show that every participant had that length of follow-up.

For participants who have not had a recorded event by the end of their available observation, or whose outcome follow-up ends for another reason, time-to-event methods can retain their observed event-free follow-up through censoring. The registry specifically describes one participant as censored after loss to follow-up. The record does not provide the median progression-free survival or its precision, so the endpoint's value cannot be interpreted from this record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a time-to-event outcome. The registry defines the event as first documented progression at any site or death from any cause, with time measured from initiation of whole brain radiotherapy with capecitabine. This definition determines which observations count as events and when the outcome clock begins. The stated timeframe is 2 years. The registry lists a median and 95% confidence interval as the outcome format, but neither the median nor the interval is reported.

What does a median time-to-event estimate describe?

In general, the median time-to-event estimate describes the point in the estimated event-time distribution by which half of the distribution has experienced the event. It is not an average, and it does not state that every participant experienced an event at that time. A confidence interval communicates uncertainty around an estimated quantity: it reflects the range of values reasonably compatible with the data under the statistical method and its assumptions. It is not a guarantee that the true value lies within the interval. Because the registry record gives no estimate or interval, neither the event-time summary nor its precision can be assessed.

How does censoring enter the analysis?

In general, censoring occurs when a participant's event time is not observed in full, although the participant contributes follow-up up to a known point. This differs from observing an event at the censoring time. Time-to-event methods can use the available event-free follow-up without treating the participant as if the event had occurred. The registry reports that one participant was lost to follow-up after 3.5 months of observation and describes the data as censored. It also says six of the seven people who stopped treatment early were followed for the survival outcome. The record does not report a complete accounting of censoring times or the method used to estimate the endpoint.

A common general method for describing time-to-event data is the Kaplan–Meier estimator. It updates the estimated probability of remaining event-free as events occur, while accounting for participants who are censored. This description is general; the registry record does not name the method used for its primary outcome. The endpoint's listed median and confidence interval are compatible with common time-to-event reporting, but the record does not specify how either would have been calculated.

What would a hazard ratio mean?

In general, a hazard ratio compares event rates over time between groups, subject to the model and assumptions used. It is not the same as a ratio of medians or a direct measure of the absolute difference in time without an event. A hazard ratio usually needs a comparison group to have a treatment contrast interpretation. This trial is recorded as single group, and the registry reports zero analyses; no sponsor-reported hazard ratio value is present. The general meaning of a hazard ratio therefore does not create a comparative result for this study.

The registry's statistical-method description says that only sponsor-reported hazard ratios are used for time-to-event outcomes. Since no analyses or hazard ratio results are reported, there is no basis for a recalculated hazard ratio. More generally, a simple re-calculation from summary statistics cannot reproduce a full time-to-event analysis when the necessary event-time and censoring information is absent. If an independently recalculated value differed from a sponsor's analysis, the sponsor's own analysis would take precedence, but no such discrepancy is reported in this record.

How should planning illustrations be read?

Sample-size calculations are planning exercises, not evidence about what a completed study demonstrated. The assumptions described for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. For time-to-event outcomes, the planning convention is to give a total event count. These are illustrations based on an observed effect, not the trial's own design justification, and they are not observed power. They should not be read as the actual design of this single-group study, which has no control arm. The registry record does not report its sample-size justification or a protocol-based statistical plan.

Over-dispersion is a general concern for some count-data models: it occurs when the observed variability exceeds what a model assumes and can make uncertainty estimates too small if ignored. It is not the central issue for this trial's primary time-to-event endpoint. The registry record does not report a count-model analysis, so no conclusion about over-dispersion or its handling is possible. The key methods limitation is more direct: no primary outcome estimate, confidence interval, or analysis method is reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It identifies progression-free survival as the primary endpoint, but does not report its median estimate or 95% confidence interval. There is no reported statistical analysis plan explaining how the primary endpoint would be estimated or how additional outcomes, if any, would be handled. A multiplicity adjustment or strategy is not reported in the registry record.

Multiplicity refers generally to the interpretive problem that can arise when several outcomes, time points, subgroups, or statistical tests are examined. The more opportunities there are to find an apparently notable result, the more important it becomes to explain which analyses were planned and how they were interpreted. This general issue cannot be evaluated from the posted record because it does not describe a testing strategy or provide analyses. The absence of a reported multiplicity method should not be taken to mean that a particular adjustment was or was not used outside the registry record.

The record reports that five patients progressed during study treatment. It also states that seven stopped treatment early due to an adverse event or withdrawal, that six of those were followed for the survival outcome, and that one was lost to follow-up after 3.5 months and censored. This is relevant to missing outcome information, but it is not a complete account of missingness: the record does not give all follow-up durations, the event status of each participant, or the approach used for missing data beyond the stated censoring description.

The registry record does not identify a formal analysis population, such as an intention-to-treat or per-protocol population. It also does not explain how withdrawals were handled in the primary analysis. Without those details and the endpoint estimate, the potential impact of missing follow-up on the result 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: cardiac - chf (8.3%), dyspnea (sob) (8.3%), hypercalcemia (8.3%), diabetetic ketoacidosis (8.3%).

The safety record lists a group titled WBRT + Capecitabine + Sunitinib, with 12 at risk for serious adverse events and 4 affected. For the other adverse-event category, it lists 12 at risk and 12 affected. These are registry group summaries; the record does not provide a comparator group, so they cannot support a relative safety comparison against another regimen or usual care.

The listed serious adverse-event terms with reported percentages are Cardiac - CHF, Dyspnea (SOB), Hypercalcemia, and Diabetetic Ketoacidosis. Each is reported as 8.3%. These are the terms identified among the top serious-event entries, not a complete narrative of every possible event or its timing. The record does not give additional information about severity grades, duration, resolution, relatedness to treatment, or whether individuals experienced more than one term.

The deaths field is not reported in the registry record. That absence should not be interpreted as evidence that no deaths occurred. Serious adverse-event counts and listed percentages are descriptive, and the record does not give the detail needed to assess comparative risk or attribute an event to a specific component of the treatment sequence.

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

The record establishes what investigators set out to study: a phase 2, single-group regimen for breast cancer with CNS metastases, using capecitabine concurrently with whole brain radiotherapy and then capecitabine with sunitinib. It also specifies a clinically relevant time-to-event endpoint that includes progression at CNS or extra-CNS sites and death. These design and endpoint details help define the intended question.

The posted record does not establish the primary outcome result. It lists progression-free survival as the primary outcome, with a median and 95% confidence interval as the reporting format, but it does not provide either value. It reports zero analyses. The participant-flow description notes five progressions during treatment and follow-up information for people who stopped treatment early, but those details cannot be converted into a median or a treatment effect without the analysis and relevant follow-up data.

The design cannot establish comparative efficacy because there is no concurrent comparator. Outcomes in a single group can be described, but they cannot show what would have happened under another treatment. The registry record also does not report a hazard ratio, and a general explanation of that statistic is not a substitute for an observed comparative analysis.

The safety entries indicate serious adverse events were recorded, including four affected in the listed safety group and four terms reported at 8.3% each. These summaries do not establish comparative safety, attribution, or the full clinical course of the events. Deaths are not reported in the registry record.

Accordingly, the record supports an understanding of the study's intended regimen, eligibility context, endpoint definition, and selected safety summaries. It does not support a conclusion that the regimen did or did not improve outcomes, nor does it provide enough information to judge the precision of the primary outcome. Absence of a reported result is not itself evidence of benefit, lack of benefit, or harm.

13. Why This Trial Matters Statistically

This study illustrates why design and outcome reporting have to be considered together. The registry names a time-to-event primary endpoint and defines what constitutes progression, including CNS and extra-CNS disease as well as death. That specificity helps readers understand what the planned outcome means. At the same time, without a reported median or confidence interval, the endpoint cannot answer how long participants remained free of progression or death in the study.

The single-group design also clarifies the limits of interpretation. A treatment sequence can be associated with outcomes observed among its participants, but a comparison group is needed to estimate a contrast against an alternative under comparable conditions. The record explicitly lacks a like-for-like control comparison. This matters especially for an outcome affected by disease course and follow-up, where an observed duration alone would not identify a causal treatment effect.

The follow-up description demonstrates why censoring and early treatment discontinuation matter in time-to-event research. The record notes both early treatment discontinuation and a participant lost to follow-up who was censored. Those details indicate that treatment exposure and outcome observation are not identical: stopping study treatment does not necessarily mean outcome follow-up stopped. But the record does not provide enough information to reconstruct the analysis or understand the full pattern of follow-up.

Finally, the registry contains safety summaries but no reported primary analysis. This separation underscores that safety counts and an efficacy endpoint answer different questions and require different interpretation. A registry entry can identify an intended clinical question and selected observations while still leaving key statistical results unavailable. For this trial, the missing primary estimate and lack of a comparator are central to understanding what can be concluded from the posted 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 is that the primary outcome estimate is not reported. Although the registry specifies a median progression-free survival and 95% confidence interval as the outcome format, it gives neither value and lists zero analyses. The result's magnitude and precision therefore cannot be evaluated from the registry record.

The study is single group, with allocation listed as not applicable and no masking. There is no concurrent control arm for a direct comparison. This means the record cannot separate outcomes associated with the regimen from other influences on disease course or care. The sample size is listed as 12 enrolled, but the registry does not report the rationale for that enrollment target or a protocol-based sample-size justification.

Follow-up information is incomplete for interpretation. The registry describes five progressions during study treatment, seven early treatment stops due to an adverse event or withdrawal, six of those followed for the survival outcome, and one person lost after 3.5 months and censored. It does not give individual event times, complete observation durations, or a full account of missing outcome data. A complete analysis population and the method for handling withdrawals are not reported.

The record also does not report the reason for termination, a statistical analysis plan, multiplicity handling, or a detailed analysis method for progression-free survival. The safety summary does not include a comparator, event timing, severity grades, treatment attribution, or a reported deaths value. These omissions constrain interpretation of both efficacy and safety and should not be filled by assumptions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Brain Mets - Capecitabine Plus Sunitinib and WBRT — NCT00570908.
• Registry record last updated 2014-09-18; status last verified 2014-08.
• Results first posted 2014-08-12.
• 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

This phase 2 trial studied capecitabine given concurrently with whole brain radiotherapy, followed by capecitabine and sunitinib, for breast cancer with CNS metastases. It is recorded as single group, with no masking, 12 enrolled, and no like-for-like control comparison. The registry lists the study status as terminated, with start recorded as 2009-02 and primary completion as 2013-09.

The primary outcome is progression-free survival, defined from initiation of whole brain radiotherapy with capecitabine to first documented progression at any site or death. The registry gives a 2-year timeframe but does not report the median estimate or 95% confidence interval. It notes five progressions during study treatment and describes early treatment discontinuation and censoring, but lists zero analyses.

The safety record lists 4 affected by serious adverse events and four serious-event terms at 8.3% each. Deaths are not reported in the registry record. The available information describes the intended question and selected safety observations, but does not provide a primary efficacy result or a comparative estimate.