A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis (NCT00977379), a randomized phase 2 study. The primary outcome is Percentage of Participants With Best Objective Central Nervous System (CNS) Response, Assessed by Centralized Independent Expert According to Magnetic Resonance Imaging (MRI) - Intent-to-Treat (ITT) Population.

2. Clinical Question

3. Trial Design

This was an open-label, randomized, parallel-group, comparative, multicentre phase II trial. The registry lists an enrollment of 24 and a terminated status. The study start is recorded as 2009-08 and primary completion as 2011-02. The reason for termination and any consequences for recruitment or follow-up are not reported in the registry record.

Participants were assigned to WBRT followed by standard-of-care therapy or to WBRT given concurrently with capecitabine, followed by capecitabine maintenance. The standard-of-care group’s later therapy was at the treating oncologist’s discretion. The radiation schedule described for both groups was 3000 cGy in 10 single daily fractions over 12 to 14 days. The registry’s arm descriptions are truncated, so details beyond the descriptions that are complete are not reported in the registry record.

The primary outcome was the percentage with best objective CNS response according to a centralized independent expert reviewing MRI. The stated assessment period ran from baseline until disease progression, unacceptable toxicity, withdrawal of consent, a change in therapeutic strategy for the standard-of-care group, or death, whichever occurred first. The registry describes the period as up to approximately 1 year 5.5 months overall. The primary outcome was designated for the intent-to-treat population.

Randomization is reported, but the method used to generate the allocation sequence, allocation concealment, stratification factors, and planned group ratio are not reported in the registry record. Masking was absent. The record lists 15 outcome measures and 13 posted secondary outcomes, but no reported analyses for the secondary outcomes. The original statistical plan, sample-size justification, and reason for stopping the trial 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:

Analysis population for the primary outcome, as defined in the registry: ITT population.

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: Intent to treat (ITT) population included all randomized participants except one participant from "WBRT+Capecitabine Followed by Capecitabine Maintenance" arm who was randomized by error.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Best Objective Central Nervous System (CNS) Response, Assessed by Centralized Independent Expert According to Magnetic Resonance Imaging (MRI) - Intent-to-Treat (ITT) Population, measured over Baseline until disease progression (PD), unacceptable toxicity, withdrawal of consent, change of therapeutic strategy (for arm "WBRT Followed by Standard of Care" only), or death, whichever occurred first (up to approximately 1 year 5.5 months overall).

The primary endpoint is the percentage of participants with a best objective CNS response, assessed by a centralized independent expert using MRI. “Best” refers to whether a participant met the response definition during the stated assessment period, rather than only at one fixed scan. The period began at baseline and ended at disease progression, unacceptable toxicity, withdrawal of consent, a change in therapeutic strategy for the standard-of-care group, or death, whichever occurred first.

The registry defines response as complete response (CR) or partial response (PR) for CNS metastasis, assessed using contrast-enhanced MRI and response evaluation criteria in solid tumors (RECIST). CR was defined as disappearance of all CNS lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of CNS lesions, using the baseline sum as the reference.

A percentage endpoint is useful for expressing how often a defined response was recorded in each randomized group. It supports a direct comparison of response proportions, while also making clear that the endpoint is a binary classification: a participant either met the response definition or did not. It does not capture the full course of disease, duration of response, or other outcomes. Those are distinct questions, and the registry lists some of them among the secondary outcomes. The posted primary response percentages do not report the timing, magnitude, or durability of each individual participant’s change.

7. Results Posted in the Registry

• WBRT+Capecitabine Followed by Capecitabine Maintenance: 36.4% (4/11) versus 25.0% (3/12) on control; risk difference 11.4 percentage points (95% CI -26.2 to 48.9), risk ratio 1.45 (0.42–5.10); unadjusted two-proportion z-test p = 0.554.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • WBRT+Capecitabine Followed by Capecitabine Maintenance: 36.4% (4/11) versus 25.0% (3/12) on control; risk difference 11.4 percentage points (95% CI -26.2 to 48.9), risk ratio 1.45 (0.42–5.10); unadjusted two-proportion z-test p = 0.554.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between WBRT+Capecitabine Followed by Capecitabine Maintenance and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • WBRT+Capecitabine Followed by Capecitabine Maintenance: 54.5% (6/11) versus 50.0% (6/12) on control; risk difference 4.5 percentage points (95% CI -36.3 to 45.4), risk ratio 1.09 (0.50–2.38); unadjusted two-proportion z-test p = 0.827.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between WBRT+Capecitabine Followed by Capecitabine Maintenance and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • WBRT+Capecitabine Followed by Capecitabine Maintenance: 72.7% (8/11) versus 83.3% (10/12) on control; risk difference -10.6 percentage points (95% CI -44.3 to 23.1), risk ratio 0.87 (0.56–1.36); unadjusted two-proportion z-test p = 0.538.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between WBRT+Capecitabine Followed by Capecitabine Maintenance and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several related but non-identical questions, including CNS response at a fixed assessment time, investigator-assessed best response, clinical benefit, duration of response, CNS progression, and extra-cranial response. They use different assessment times or assessors, and some address outcomes beyond response proportions. Their results therefore need not move in parallel with the primary endpoint.

Among the secondary results with posted arm-level estimates, the direction of the comparison is not consistent across every outcome: some estimates are higher in the capecitabine group, while another is higher in the standard-of-care group. This variation does not by itself demonstrate a treatment effect or an inconsistency in the trial; endpoints differ in definition and assessment. The fixed-time centralized response result follows the same pattern and values as the primary response result, so it is not an independent confirmation of that finding.

The other listed secondary outcomes are not accompanied by posted analyses in the registry record. In particular, listed measures of response duration, time to CNS progression, and extra-cranial response cannot be interpreted from outcome names alone. Their results and uncertainty are not reported in the registry record.

Unadjusted secondary results generally carry less weight than a prespecified primary analysis because examining multiple outcomes increases the chance that some apparent differences arise by chance. In general, adjustment for multiplicity or a clearly ordered testing strategy can address this concern, but the registry does not report whether either was planned or used. The available secondary findings are best treated as contextual and exploratory; they do not resolve the uncertainty in the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI
• Percentage of Participants With Best Objective CNS Response, Assessed by Investigator According to MRI
• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Centralized Independent Expert According to MRI in 3 Dimension
• Percentage of Participants With Clinical Benefit, Assessed by Investigator According to MRI
• Percentage of Participants With Objective CNS Response at 4 Weeks After Completion of WBRT, Assessed by Investigator According to MRI
• Duration of CNS Response, Assessed by Investigator According to MRI
• Time to CNS Progression, Assessed by Investigator According to MRI
• Percentage of Participants With Best Objective Extra-cranial Disease Response, Assessed by Investigator According to Computed Tomography (CT)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary result is a binary outcome summarized as a percentage in each randomized group. Each participant is classified according to whether the prespecified response definition was met. The registry’s response categories are CR and PR, assessed by contrast-enhanced MRI under RECIST. This kind of endpoint is straightforward to summarize, but it compresses a complex clinical course into a yes-or-no status. It does not describe how long a response lasted or how a participant’s disease changed at other sites.

How to interpret the group proportions

The registry reports 25.0% for WBRT followed by standard of care and 36.4% for WBRT plus capecitabine followed by capecitabine maintenance. The denominators are 12 and 11, respectively. A proportion is the observed share of the analyzed group meeting the endpoint. In groups this small, the status of even a few participants can have a noticeable influence on the percentage. That makes the point estimates sensitive to the particular participants enrolled and supports cautious interpretation.

The posted comparison includes an unadjusted p-value of 0.554. In general, a p-value measures how compatible the observed data are with a specified null model, assuming that model and the test’s assumptions apply. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. An unadjusted result also does not account for other outcomes or multiple testing unless such an adjustment is explicitly part of the method. The statistical plan and any multiplicity procedure are not reported in the registry record.

What a confidence interval adds

In general, a confidence interval gives a range of effect values compatible with the data under a stated statistical procedure. It conveys precision as well as direction: a narrow interval indicates greater precision than a broad one. For this comparison, the posted interval for the risk difference extends across no difference, with values on both sides. The interval is broad, so the observed data do not precisely determine the direction or size of the population difference. The exact confidence-interval method is not reported in the registry record.

For a binary endpoint, the risk difference compares the response proportions on an absolute scale. Other relative measures, such as a risk ratio or odds ratio, answer a related but different question by expressing the comparison relative to the comparator group. The registry contains recalculated unadjusted comparisons, but they are not a substitute for a sponsor-reported analysis. The discrepancy flag is false, so there is no registry-identified disagreement requiring precedence of a sponsor analysis; no sponsor-reported analysis is listed for this endpoint.

Why assessment and allocation matter

Randomization is intended, in general, to make treatment groups comparable at assignment with respect to both measured and unmeasured characteristics. Its protections depend on implementation and follow-up, details that are not fully reported in the registry record. Open-label assignment means the treatment was not masked. The primary outcome was assessed by a centralized independent expert, which may help standardize image-based classification, but the registry does not report the expert’s procedures, blinding to treatment, or handling of ambiguous scans.

The primary population is identified as intent-to-treat (ITT). In general, an ITT approach analyzes participants according to their randomized assignment, whether or not they fully received the assigned treatment. This preserves the randomized comparison when applied consistently. The registry does not give a detailed account of the ITT implementation, participant exclusions, missing MRI assessments, or how missing outcome values were handled. The arm denominators posted for the endpoint are 12 and 11; the record does not explain the relationship between these denominators and the enrollment entry.

Reading the analysis in context

The primary endpoint covers best response over a follow-up period that could extend to approximately 1 year 5.5 months overall, subject to the stated stopping events. The registry does not report the number or timing of MRI assessments per participant, the completeness of follow-up, or a detailed analysis plan. These omissions limit assessment of how consistently participants had the opportunity to demonstrate a best response. They also make it difficult to judge whether the posted summary reflects all randomized participants as intended.

The secondary outcomes include response at a fixed time, investigator-assessed response and clinical benefit, response duration, CNS progression, and extra-cranial response. These outcomes address different aspects of disease and use different assessment approaches. Each can add context, but multiple outcomes create opportunities for chance findings when many comparisons are examined. General statistical practice treats unadjusted secondary findings as exploratory unless the analysis plan establishes how they are prioritized and interpreted. Such a plan is not reported in the registry record.

11. Confidence Intervals and Precision

The primary response proportions are based on small posted denominators: 12 in the WBRT-followed-by-standard-of-care group and 11 in the WBRT-plus-capecitabine group. With limited observations, each participant’s response classification has substantial influence on the group percentage. The estimates should therefore be read as imprecise summaries rather than stable estimates of response in a wider population.

The registry’s confidence interval for the risk difference is broad and includes values on both sides of no difference. In general, an interval that includes no difference does not establish that the groups are equal; it indicates that the data are compatible with no difference as well as with differences in either direction under the interval procedure. Its breadth is important: the observed proportions do not tightly constrain the size of the population effect. The exact interval method is not reported in the registry record.

The unadjusted p-value is 0.554. It is consistent with the uncertainty conveyed by the interval, but the p-value and interval answer different questions and should be considered together with the effect estimate. Neither establishes whether a difference would be clinically important. The registry does not report a prespecified threshold for clinical importance or a formal equivalence or non-inferiority framework.

Precision is also affected by the trial’s status and reporting detail. The registry records termination, while the reason, planned recruitment target, and completeness of follow-up are not reported in the registry record. Those omissions prevent a full assessment of whether the amount of information was expected or whether endpoint ascertainment was complete. The evidence supports a cautious description of the observed group results, not a precise estimate of a general treatment effect.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the original design assumptions for this trial. For these binary outcomes, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a future study to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column uses a higher chance of detection and therefore requires more participants per arm for the same stated effect. These are planning values, not observed power for the completed trial. Observed power is not a useful substitute for interpreting the uncertainty in the result already obtained.

Rows describing planning for 100% of the observed effect use the full observed estimate as the target for a hypothetical study. Rows for 75% and 50% of the observed effect plan for smaller effects. Smaller effects require more participants because they are harder to distinguish from random variation when other assumptions remain the same. The displayed values are therefore sensitive to the effect chosen as the planning target. Since the observed estimate comes from a small trial and is uncertain, it should not be treated as a reliable prediction of the effect a future study will see.

The registry does not report the assumptions used to design the original trial, nor does it state that the posted planning illustrations guided enrollment or termination. These figures should be read only as conditional planning scenarios under the listed assumptions. They do not show that the completed study had a particular probability of detecting an effect, and they do not establish what sample size would be appropriate without a separate design rationale.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.250; treatment proportion p₁ = 0.364; average p̄ = 0.307.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6522 = 1.2783.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6472 = 0.5447.
4. n = (1.2783 + 0.5447)² / (0.1136)² = 257.4, rounded up to 258 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.25                          # control proportion
p1 <- 0.363636363636364                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(977379)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 258 (80% power), 345 (90% power)
 75% of observed effect: n per arm = 447 (80% power), 597 (90% power)
 50% of observed effect: n per arm = 976 (80% power), 1,306 (90% power)
power.prop.test: 257.4 
Simulated power at n = 258 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including a primary endpoint and multiple secondary outcomes. It does not report a multiplicity strategy, such as an adjustment to control the overall chance of false-positive findings or a hierarchy specifying which outcomes would be tested first. Without that information, separate unadjusted results across several endpoints should not be treated as if each were the only comparison planned.

No sponsor-reported analyses are listed for the posted secondary outcomes. The record includes unadjusted recalculations for some binary comparisons, but it does not identify a full statistical analysis plan or indicate how secondary analyses were selected. The significance threshold for the trial’s own planned analyses, any covariate adjustment, subgroup analyses, or interim analyses is not reported in the registry record. No interim analyses or stopping rules should be inferred from the terminated status.

The primary endpoint is identified as applying to the ITT population. In general, ITT analysis retains participants in their randomized groups and helps preserve the benefit of randomization. The registry does not report detailed participant flow, exclusions, treatment adherence, or the analysis population used for each outcome. Although arm denominators are posted for the primary result, the record does not explain their relationship to the enrollment entry.

Missing outcome data can affect a binary response comparison if participants with unavailable assessments differ from those with observed assessments. The registry does not report the number of missing MRI evaluations, reasons for missingness, imputation methods, or sensitivity analyses. These details are important because the primary outcome depends on imaging assessment over follow-up. The record also does not describe whether participants who stopped treatment continued outcome assessment.

The study is recorded as terminated, but its reason and timing relative to recruitment and analysis are not reported in the registry record. Termination alone does not establish that stopping was related to the results. Without the reason, stopping criteria, and planned analysis information, it is not possible to assess whether the termination or incomplete reporting could have influenced the evidence available for interpretation.

15. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: general physical health deterioration (18.2%), colitis (9.1%), depressed level of consciousness (9.1%), epilepsy (9.1%), intracranial pressure increased (9.1%).

The registry reports serious adverse events affecting 6 of 12 participants in the WBRT-followed-by-standard-of-care group and 6 of 11 in the WBRT-plus-capecitabine group. Other adverse events are recorded for 11 of 12 and 10 of 11 participants, respectively. These counts describe the posted safety groups; the registry excerpt does not provide event-level detail for all events or a comparison adjusted for follow-up time.

The listed serious adverse-event terms include general physical health deterioration at 18.2%, and colitis, depressed level of consciousness, epilepsy, increased intracranial pressure, and syncope at 9.1% each. These are registry-listed percentages for the named terms and should not be interpreted as a complete account of the nature, timing, severity, or duration of adverse events. The record does not report deaths in the safety summary.

Safety counts in small groups are descriptive and do not establish comparative risk. The registry does not report exposure-adjusted rates, detailed event timing, or a formal statistical safety comparison. The figures should be read alongside the limitations in follow-up and reporting, not as a complete evaluation of safety.

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

The posted primary result describes the proportion of participants classified as having a best objective CNS response in each randomized group. The observed percentages are 25.0% for WBRT followed by standard of care and 36.4% for WBRT with concurrent capecitabine followed by capecitabine maintenance. The unadjusted p-value is 0.554, and the risk-difference interval spans no difference. Together, these results do not provide a precise or conclusive estimate of the comparative effect.

That interpretation is different from saying the treatments are the same. The data do not establish equivalence, and the wide uncertainty leaves room for differences in either direction. A result that is not statistically significant does not prove absence of an effect. Conversely, the higher observed percentage in one group does not establish that the assigned regimen caused a higher response rate. The small posted denominators and broad interval make both overconfident conclusions inappropriate.

The primary outcome is an MRI-based response classification, not a direct measure of all aspects of health or disease course. It does not, on its own, establish duration of response, time to progression, quality of life, or the balance of benefits and harms. The registry lists some additional outcome questions, but results for many are not reported. The endpoint also does not provide a complete safety comparison.

General interpretation of randomized trials depends on adequate implementation, complete follow-up, prespecified analyses, and transparent reporting. The registry identifies randomization and the ITT population for the primary endpoint, but does not report key details about allocation methods, missing data, the original statistical plan, or the reason for termination. These gaps limit the strength of conclusions that can be drawn from the posted record.

The defensible conclusion is limited to what was observed: response proportions were recorded in both groups, and the available comparison is imprecise. The result does not establish that adding capecitabine improves response, does not establish that it has no effect, and does not support a clinical recommendation. It is one small, terminated phase II trial with incomplete reporting of important design and analysis details.

17. Why This Trial Matters Statistically

This trial illustrates why a response percentage should be interpreted together with its uncertainty. The two posted percentages may appear separated, but the group denominators are small and the confidence interval for the comparison spans no difference. A point estimate alone can give a misleading impression of certainty, particularly when individual outcome classifications have a strong influence on the group summary.

It also demonstrates the distinction between a primary and secondary endpoint. The primary endpoint was assessed centrally, while some secondary outcomes relied on investigator assessment or used different timing and definitions. Such outcomes can contribute context, but they do not all answer the same question. When many outcomes are examined, an unadjusted result should be interpreted cautiously unless the analysis plan explains how multiplicity was handled.

The registry record also highlights the difference between a trial’s own design calculations and later planning illustrations based on an observed effect. The latter depend on assumptions and on an uncertain estimate from the trial; they cannot explain the original enrollment decision or indicate the completed trial’s observed power. Here, original design assumptions are not reported.

Finally, registry entries may identify important limitations that are not resolved by the headline result: termination status, incomplete outcome reporting, absent sponsor-reported analyses, and missing information about missing data and analysis procedures. Those factors do not invalidate the posted observations, but they constrain the claims those observations can support. Statistical interpretation requires attention to both the numerical estimate and the completeness of the evidence record.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry records a terminated trial, but the reason for termination and its timing relative to recruitment, follow-up, or analysis are not reported in the registry record. The overall enrollment entry is 24, while the posted primary arm denominators are 12 and 11; the record does not explain this relationship. Participant flow, exclusions, and the number completing imaging assessments are not reported.

The primary endpoint is specified for the ITT population, but the registry does not describe how ITT was implemented, whether all randomized participants had evaluable MRI results, or how missing endpoint data were handled. It also does not report the allocation-generation method, concealment procedures, stratification, treatment adherence, or whether the central image reviewer was unaware of treatment assignment. Open-label treatment assignment is reported.

The posted comparison is an unadjusted recalculation, and sponsor-reported analyses are not listed. The original statistical analysis plan, sample-size justification, multiplicity approach, interim analyses, and stopping rules are not reported in the registry record. This makes it difficult to assess how closely the posted results correspond to the originally intended analysis.

The registry lists several secondary outcomes, but reports analyses for only a subset. Results for duration of CNS response, time to CNS progression, and extra-cranial response are not reported in the registry record. The safety summary provides selected counts and listed serious-event terms, but not detailed event timing, duration, exposure-adjusted rates, or a complete event-level account. These reporting limitations narrow the conclusions that can be drawn beyond the primary descriptive result.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of Whole Brain Radiation Therapy and Capecitabine in Breast Cancer Participants With Newly Diagnosed Brain Metastasis — NCT00977379.
• Registry record last updated 2016-11-15; status last verified 2016-09.
• Results first posted 2016-11-15.
• 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.

22. Record Summary

This open-label, randomized, parallel-group phase II trial compared WBRT followed by standard-of-care therapy with WBRT plus concurrent capecitabine followed by capecitabine maintenance in breast cancer participants with newly diagnosed brain metastases. The registry records an enrollment of 24 and a terminated status.

The primary outcome was best objective CNS response assessed centrally by MRI in the ITT population. The posted proportions were 25.0% and 36.4%, with an unadjusted p-value of 0.554 and a broad interval spanning no difference. The results are descriptive and imprecise; they do not establish a clear comparative effect.

The reason for termination, original design assumptions, missing-data procedures, and multiplicity plan are not reported in the registry record. Several listed secondary outcomes have no posted analyses. These limitations should inform interpretation of both the efficacy and safety summaries.