STAR Cape+BKM120 MBC With Brain Met: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for STAR Cape+BKM120 MBC With Brain Met (NCT02000882), a na phase 2 study. The primary outcome is Clinical Benefit Rate (CBR).

2. Clinical Question

The registry describes a phase II multicenter single-arm study of BKM120 plus capecitabine for breast cancer patients with brain metastases. Its stated purpose was to determine safety and effectiveness in this population. The regimen description allows trastuzumab for patients with HER2+ metastatic breast cancer only, so the treatment details were not identical for every participant.

The primary question is a within-group question: what proportion of evaluable patients met the clinical benefit definition after the specified treatment? It is not a randomized comparison of the combination against another treatment, and the record does not support a causal comparison with a control group. The primary endpoint description specifies assessment following WBRT or SRS, or both, and refers to RECIST 1.1 for response assessment.

Although the registry gives the endpoint definition and an enrollment of 10, it does not report the observed clinical benefit rate, the number of evaluable patients, or a confidence interval. Therefore, the record does not show how many patients met the primary endpoint or how precisely that proportion was estimated. Results for the listed secondary outcomes are also not reported in the registry record.

3. Trial Design

This was a phase II, multicenter, single-group study sponsored by US Oncology Research. The registry lists the study as completed, with a start date of 2014-05-29 and a primary completion date of 2019-03-29. Enrollment was 10. The allocation is listed as not applicable, and masking is listed as none; these entries are consistent with the stated single-group design rather than a blinded randomized comparison.

The treatment group is described as BKM120 plus capecitabine. BKM120 was to be administered orally at 100 mg daily. Capecitabine was to be administered orally at 1000 mg/m2 twice a day, rounded down to the nearest 500 mg pill, on a schedule of 14 days on and 7 days off. For patients with HER2+ metastatic breast cancer only, the description includes standard every-3-weekly trastuzumab at 6 mg/kg IV. The trastuzumab description ends mid-instruction in the registry record, so additional administration details are not reported in the registry record.

The primary endpoint was clinical benefit rate, with response assessed by RECIST 1.1. The stated observation period continued until disease progression, unacceptable toxicity, death, or discontinuation for another reason, up to 2 years from patient registration. The endpoint definition refers to patients following WBRT or SRS, or both.

A single-group design can describe outcomes among people receiving a regimen, but it does not directly estimate how outcomes would differ under another treatment or under no treatment. No random allocation or concurrent control is reported. The registry does not report the protocol’s sample-size justification, eligibility details beyond the stated condition and endpoint context, or an analysis plan. The record lists secondary outcomes, including objective response rate, median time to progression, median overall survival, and treatment-related serious adverse events, but their results 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

Reasons for not completing this period:

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 Clinical Benefit Rate (CBR), measured over until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration.

The primary endpoint is clinical benefit rate. It is defined as the number of evaluable patients with a complete response, partial response, or stable disease lasting at least 24 weeks, divided by the total number of evaluable patients. Response is assessed by RECIST 1.1. A complete response requires disappearance of all target lesions, with pathological lymph nodes reduced to less than 10 mm in short axis. A partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to the baseline sum.

This endpoint combines tumor shrinkage with sustained disease stability. That can be useful when the clinical question includes whether disease is controlled for a specified period, rather than counting only complete or partial responses. The stable-disease component is time-dependent: a patient must meet the stability criterion for at least 24 weeks to count toward clinical benefit. The endpoint is a proportion, so its interpretation depends on the number of patients who were evaluable as well as the number who met the definition.

The registry specifies a 90% confidence interval for the endpoint and an assessment period that can extend up to 2 years from registration, ending earlier for progression, unacceptable toxicity, death, or other discontinuation. However, the observed clinical benefit rate, the evaluable denominator, and the confidence interval are not reported in the registry record. The record therefore defines what was intended to be measured, but does not provide the result needed to describe the observed clinical benefit rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary patient-level outcome: each evaluable patient either meets the clinical benefit definition or does not. The registry defines a patient as meeting that definition through complete response, partial response, or stable disease lasting at least 24 weeks. The clinical benefit rate is the proportion meeting the definition among evaluable patients. This is distinct from a continuous measure such as a change in tumor size, and it is distinct from a time-to-event measure such as time to progression.

What does the confidence interval describe?

The registry specifies a 90% confidence interval for clinical benefit rate. In general, a confidence interval expresses the uncertainty associated with an estimate under the statistical method used. For a proportion, the interval depends on the observed number meeting the endpoint and the denominator assessed. Wider intervals indicate less precision; narrower intervals indicate greater precision under the method’s assumptions. The registry record does not report the observed proportion, the evaluable denominator, or the method used to calculate the interval. It therefore does not allow the interval’s width or coverage method to be evaluated.

A confidence interval is not a guarantee that the true value lies within its particular limits, and it does not substitute for the estimate itself. In a small study, each participant can have a substantial influence on a proportion, so the denominator and the uncertainty interval are important context. The enrollment of 10 is reported, but the endpoint denominator may be the evaluable population rather than all enrolled participants. The number evaluable is not reported in the registry record, so the relationship between enrollment and the primary endpoint denominator is unknown.

How does the design shape interpretation?

In a single-group study, the primary endpoint can be described as an outcome proportion in the treated group. There is no randomized comparison to estimate a between-group treatment contrast. A proportion from this design cannot by itself distinguish the effects of the regimen from other explanations for observed outcomes. This is a feature of the design, not a calculation problem that can be resolved by a confidence interval.

RECIST 1.1 supplies the stated response framework. The complete response definition concerns disappearance of target lesions and reduction of pathological lymph nodes to less than 10 mm in short axis. The partial response definition concerns a decrease in the sum of target-lesion diameters relative to baseline. Stable disease contributes to clinical benefit only when it lasts at least 24 weeks. Thus, the endpoint combines an assessment of tumor response with a duration requirement for stable disease. The registry does not report further operational details about assessment timing, independent review, or handling of ambiguous assessments.

What can be inferred from planning illustrations?

The planning assumptions described for sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe detecting a stated fraction of an observed effect; for time-to-event outcomes, the stated quantity is a total number of events, while other outcomes use participants per arm. These are planning illustrations based on an observed effect, not the trial’s own design justification. They do not turn this single-group study into a two-arm comparison, and they are not observed power. The registry does not report the study’s own sample-size justification.

Planning calculations answer a different question from the trial’s observed result. They can illustrate how assumptions about an effect and statistical criteria relate to a future study’s size, but they do not establish that an effect is real, clinically important, or precisely estimated in the trial under review. No additional assumptions about the trial’s design should be inferred from the planning framework.

What analysis details remain unknown?

The record lists no analyses. The statistical method for the primary confidence interval, the rule for classifying patients with incomplete assessments, and the treatment of missing endpoint information are not reported in the registry record. The analysis population definition beyond evaluable patients is not reported in the registry record. The record also does not state whether any interim analyses were planned or conducted, or whether the endpoint analysis was adjusted for other outcomes. These omissions limit reproducibility and make it impossible to determine how endpoint availability or analysis choices may have affected the result.

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("BKM120 Plus Capecitabine")
n      <- c(10)
events <- c(0)
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  BKM120 Plus Capecitabine  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses more than one outcome or performs several statistical tests. The registry lists clinical benefit rate as the primary endpoint and lists objective response rate, median time to progression, median overall survival, and treatment-related serious adverse events as secondary outcomes. It does not report a strategy for controlling multiplicity, such as a hierarchy among outcomes or an adjustment to statistical testing. Such a strategy is not reported in the registry record. The registry also reports no analyses, and results for the listed secondary outcomes are not reported in the registry record.

Missing data can affect a proportion when some enrolled patients do not have an evaluable endpoint. The primary endpoint is defined using evaluable patients, but the number evaluable and the handling of patients without sufficient assessment are not reported in the registry record. The record does not specify whether missing assessments were excluded, treated as failures, imputed, or handled by another rule. No assumptions about the reasons for missingness or its consequences can therefore be checked.

The analysis population is also not fully described. The registry gives enrollment as 10 and defines the endpoint denominator as evaluable patients, but it does not report the endpoint denominator or a detailed population definition. The record does not state whether the primary analysis included all enrolled participants or only those satisfying additional analysis criteria. It does not report a sensitivity analysis for missing outcomes.

These omissions matter because the estimated proportion and its uncertainty depend on who is included and how unavailable outcomes are handled. Without the denominator, missing-data rules, and multiplicity plan, the reported design and endpoint definition are not enough to reconstruct or assess the planned analysis. The observed primary result itself is not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (20.0%), urinary tract infection (20.0%), colitis (10.0%), dysphagia (10.0%), nausea (10.0%).

For the BKM120 plus capecitabine group, the registry reports 10 participants at risk for serious adverse events and 7 affected. For other adverse events, it reports 10 at risk and 10 affected. The listed death count is 7. These are descriptive counts in a group with an enrollment of 10. The registry does not establish from these figures alone whether each event or death was caused by study treatment.

The serious adverse-event terms listed are seizure and urinary tract infection, each at 20.0%, and colitis, dysphagia, nausea, and vomiting, each at 10.0%. These percentages describe the listed terms in the registry record; they should not be treated as a complete account of the severity, duration, timing, recurrence, or clinical course of each event. The record does not provide patient-level detail or a comparison group for interpreting relative risk.

Serious adverse events are not interchangeable with all adverse events. The registry separately reports affected counts for serious and other adverse events, and it lists treatment-related serious adverse events as a secondary outcome. The specific causal attribution for the group counts is not established by the summary figures. The listed death count should likewise be read as a reported count, not as proof that the deaths were treatment-related.

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

The record establishes that a phase II multicenter single-group study evaluated a regimen of BKM120 plus capecitabine in breast cancer patients with brain metastases, with trastuzumab included for patients with HER2+ metastatic breast cancer only. It specifies clinical benefit rate as the primary endpoint and gives the response criteria and observation period. It also reports selected adverse-event counts and serious adverse-event terms.

Those details describe what the study intended to assess and some of the safety information recorded. They do not provide the observed clinical benefit rate, its 90% confidence interval, the number of evaluable patients, or results for the listed secondary outcomes. Consequently, the record does not show the magnitude or precision of the primary endpoint result. It also does not permit a quantitative assessment of objective response, time to progression, overall survival, or treatment-related serious adverse events.

The single-group design limits what any observed outcome could establish. Without a concurrent comparator, the record cannot provide a randomized estimate of how outcomes differ between the regimen and another approach. A descriptive outcome in the treated group is not equivalent to a treatment effect relative to a control group. The record does not contain information that resolves this design limitation.

The adverse-event counts should be interpreted as descriptive reports. They do not by themselves establish causation, comparative safety, or the full clinical details of individual events. The registry does not report enough information to evaluate the timing or duration of events, or how reported deaths relate to treatment.

The central statistical conclusion is therefore about the limits of the registry record: it documents the study design, planned endpoint, regimen, and some safety counts, but it does not report the primary endpoint result. No conclusion about the observed clinical benefit rate or a comparative treatment effect can be drawn from the information recorded.

14. Why This Trial Matters Statistically

This study raises several useful statistical issues for reading small single-group clinical trials. First, the distinction between enrollment and the endpoint denominator is important. Enrollment was 10, while clinical benefit rate is defined among evaluable patients. Because the evaluable count is not reported in the registry record, readers cannot determine the denominator for the intended primary estimate or judge how much endpoint information was available.

Second, the endpoint combines response categories with a duration criterion. Complete and partial response are based on RECIST 1.1 criteria, while stable disease counts only when it lasts at least 24 weeks. That structure makes the endpoint more than a simple snapshot of tumor status: it incorporates time under observation. Clear reporting of the assessment schedule and the handling of patients who discontinue or lack sufficient follow-up is therefore important, but those details are not reported in the registry record.

Third, a single-group proportion has a different interpretation from a randomized treatment contrast. It can describe outcomes in the treated group, but it does not isolate what would have happened under another treatment. Statistical precision, even when reported through a confidence interval, would not remove that design limitation.

Finally, the record illustrates why outcome definitions and outcome results must both be available. The primary endpoint is defined in detail, but its estimate and interval are absent. Without those results, readers cannot assess the observed proportion or its precision. The safety counts remain useful descriptive information, but they cannot substitute for the missing primary efficacy result or create a comparison that the design does not contain.

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 registry record has several trial-specific reporting limitations. Most importantly, it does not report the observed clinical benefit rate, the 90% confidence interval, or the number of evaluable patients. Although the endpoint definition states that the denominator is the evaluable population, the record does not provide that population’s size or explain how evaluability was determined.

The study is single-group, with no allocation and no masking. There is no concurrent control group described, so outcomes cannot be interpreted as a randomized comparison. The record also does not report the protocol’s sample-size justification, a detailed statistical analysis plan, a confidence-interval calculation method, or a strategy for handling multiplicity.

Missing-data procedures are not reported in the registry record. It is not stated how patients without adequate endpoint assessment were handled, whether sensitivity analyses were conducted, or whether analysis populations differed from the evaluable population. Interim analyses are not reported in the registry record.

The registry lists several secondary outcomes but does not report their results. Safety reporting includes affected counts, a death count, and selected serious adverse-event terms, but does not provide patient-level timing or duration, detailed event narratives, or a comparative safety assessment. The registry’s treatment description for trastuzumab ends mid-instruction, so additional administration details are not reported in the registry record.

These gaps restrict independent assessment of the primary endpoint, the analysis population, and the relation between observed events and treatment. They also mean that the completed status of the study should not be mistaken for complete reporting of its planned results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: STAR Cape+BKM120 MBC With Brain Met — NCT02000882.
• Registry record last updated 2022-02-07; status last verified 2022-01.
• Results first posted 2022-02-01.
• 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

NCT02000882 is a completed phase II multicenter single-group study sponsored by US Oncology Research. It enrolled 10 breast cancer patients with brain metastases and evaluated BKM120 plus capecitabine, with trastuzumab included for patients with HER2+ metastatic breast cancer only. The registry lists no allocation and no masking.

The primary endpoint was clinical benefit rate, defined as complete response, partial response, or stable disease lasting at least 24 weeks among evaluable patients, with response assessed by RECIST 1.1. The registry specifies a 90% confidence interval and an observation period up to 2 years from registration. The observed endpoint result, confidence interval, and evaluable denominator are not reported in the registry record.

The record reports 7 serious adverse-event-affected participants among 10 at risk, 10 participants affected by other adverse events among 10 at risk, and 7 deaths. It lists seizure and urinary tract infection at 20.0% each, and colitis, dysphagia, nausea, and vomiting at 10.0% each. Results for the listed secondary outcomes are not reported in the registry record.