Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer (NCT01023958), a na phase 2 study. The primary outcome is Objective Tumour Response According to RECIST Criteria.

2. Clinical Question

3. Trial Design

This was an open-label, single-arm Phase II trial of intravenous BI 6727 (volasertib). The registry describes the intended population as patients with locally advanced, metastatic or recurrent urothelial cancer after failure of prior chemotherapy. The official title specifies cancer of the bladder, renal pelvis or ureters; the brief summary refers to failure of first-line or adjuvant/neoadjuvant chemotherapy. The record does not give more detailed eligibility criteria.

The listed enrollment is 50. This is the registry enrollment figure and should not be read as evidence that every enrolled participant received treatment or contributed to every endpoint. The primary endpoint population is labelled TS, but the label is not expanded in the registry record. Counts contributing to the primary response result are not reported in the registry record.

The study is marked completed. Its start date is 2009-11-19 and its primary completion date is 2011-09-19. These registry dates describe the study timeline; they do not supply an endpoint result or explain how follow-up and data collection proceeded for each participant.

There was no randomized allocation, masking or parallel control arm. The single arm was described as open-label, meaning the record does not describe treatment assignment as concealed from participants or investigators. Dose and administration details beyond intravenous infusion, rules for stopping or changing treatment, and any protocol-defined interim assessments are not reported in the registry record. The record lists 24 outcome measures and zero posted analyses. It also lists progression-free survival, overall survival, response duration, disease control measures and pharmacokinetic outcomes among secondary outcomes.

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: An open-label, single-arm, Phase II trial of intravenous volasertib (BI 6727) in patients with locally advanced, metastatic or recurrent urothelial cancer of the bladder, renal pelvis, or ureters after failure of prior chemotherapy.

Overall Study

Reasons for not completing this period:

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

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: Treated set (TS) which included all patients who received at least one dose of trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Objective Tumour Response According to RECIST Criteria, measured over From first drug administration until end of study, up to 2 years.

The primary endpoint is objective tumour response according to RECIST 1.1. It counts participants with either a complete response (CR) or a partial response (PR), then expresses that outcome as a percentage of participants. The registry gives the assessment period as from first drug administration until end of study, up to 2 years.

In general, an objective response endpoint uses predefined categories to distinguish tumour shrinkage that meets specified criteria from other observed outcomes. Combining CR and PR into a response measure gives a study a way to describe tumour changes during treatment under a stated assessment framework. RECIST 1.1 supplies standardized response criteria; the registry description does not give the trial's detailed imaging schedule, confirmation rules or assessment procedures.

A percentage communicates the proportion meeting the endpoint in the population assessed. Its interpretation depends on both the number of participants meeting the response definition and the denominator used. Neither the response count, denominator, percentage estimate nor 95% confidence interval is reported in the registry record. Consequently, the endpoint definition and timeframe are available, but the size and precision of the observed response result cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response percentage represent?

For a binary endpoint, each assessed participant is classified according to whether the defined event occurred. Here, the event is an objective tumour response, specifically CR or PR under RECIST 1.1. A percentage is formed from the number meeting the definition relative to the relevant assessed population. In general, this is a compact description of frequency, but it depends on a clearly specified numerator and denominator. The response numerator and denominator are not reported in the registry record, so the response percentage cannot be reconstructed or checked.

What would a confidence interval add?

The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint, but does not report its limits. In general, a confidence interval communicates statistical uncertainty around an estimate. It is not a range containing a fixed share of individual participant outcomes, and it does not correct for a study's design limitations. A narrower interval generally indicates greater precision under the method's assumptions; an interval alone does not establish a causal effect or show that a result is clinically important. Without the estimate and interval, neither the direction nor precision of the primary result can be assessed.

Why does the single-group design matter?

A single-group study estimates outcomes among participants receiving the study intervention. Because no concurrent control group is listed, there is no randomized within-trial contrast that separates the intervention's effect from other influences on outcomes. General comparisons with external results can be informative only when populations, endpoint definitions, follow-up and care are sufficiently comparable, and even then they do not have the protection of randomization. The registry record does not describe an external comparator or comparative analysis.

What do open-label and unmasked mean for interpretation?

The record describes the study as open-label and masking as none. In general, masking can reduce the possibility that knowledge of treatment assignment influences assessment or participant and clinician behaviour. Its importance varies by endpoint. An objective response criterion can help standardize outcome classification, but the record does not specify who assessed scans, whether assessments were independently reviewed, or whether review was blinded. Those details are not reported in the registry record and should not be inferred.

How should statistical significance and planning illustrations be understood?

The registry record does not report primary-outcome hypothesis tests, p-values, analysis methods or a trial-specific sample-size justification. A separate planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. It is explicitly a planning illustration computed from the observed effect, not the trial's own design. For non-time-to-event outcomes, the stated planning quantities are participants per arm; time-to-event illustrations use total events. These assumptions do not describe this single-arm trial's allocation or establish that its design was powered for a particular result. Such sample-size illustrations are planning calculations, never observed power.

In general, a significance test addresses compatibility between data and a specified null model under the assumptions of the test. It does not measure the probability that a treatment works, nor does a non-significant result prove equivalence. No trial-specific test or p-value for the primary endpoint is reported in the registry record, so those interpretations cannot be applied to a posted numerical result.

What can be inferred from the analysis record?

The registry lists 24 outcome measures and zero analyses. An outcome measure is a planned or recorded outcome construct; an analysis is a statistical result with an associated method or estimate. The number of listed measures does not indicate that results are available for each one. With no posted analyses, methods such as covariate adjustment, handling of repeated assessments, or approaches to time-to-event censoring cannot be attributed to the trial. These are not reported in the registry record.

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("Volasertib (BI 6727)")
n      <- c(50)
events <- c(7)
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  Volasertib (BI 6727)  50  7  14.0  5.8  26.7  7.0  26.2  7.0  26.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures, including the primary objective response endpoint and secondary outcomes for progression-free survival, overall survival, response duration, disease control and pharmacokinetic measures. Considering several outcomes can raise multiplicity concerns: in general, the chance of at least one apparently unusual result can increase when many hypotheses are tested. Appropriate interpretation depends on which outcomes were prespecified as confirmatory, how testing was ordered, and whether any adjustment or other multiplicity strategy was used. Such a strategy is not reported in the registry record.

The record lists zero analyses. It therefore does not supply outcome-specific estimates, hypothesis tests, analysis populations or a testing hierarchy. It is not possible to determine from the record which outcomes were analyzed, whether analyses followed a prespecified plan, or whether results were selected for reporting.

Missing-data methods and the handling of participants without evaluable response assessments are not reported in the registry record. The record identifies the primary population as TS but does not expand that label or state how participants entered that population. It also does not report the number assessed for response, the denominator used, reasons for missing assessments, or rules for classifying unevaluable outcomes. In general, these details matter because different denominators or assumptions about missing outcomes can change a percentage and its uncertainty.

The registry does not report whether participants were analyzed according to an intention-to-treat principle, a treated population, or another analysis set. No specific imputation, censoring or sensitivity-analysis approach should therefore be assumed.

12. 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: anaemia (4.0%), urinary tract infection (4.0%), decreased appetite (4.0%), dehydration (4.0%), hyponatraemia (4.0%).

The safety record lists 50 at risk for the Volasertib (BI 6727) group. It reports 13 participants affected by serious adverse events and 49 affected by other adverse events. These are counts for a single treated group, without a control group for comparison. The record's deaths field has no reported value; deaths are not reported in the registry record.

The listed serious adverse event terms are anaemia, urinary tract infection, decreased appetite, dehydration, hyponatraemia and transitional cell carcinoma, each reported as 4.0%. These term-level percentages should be read as separate entries, not added together: a participant may have more than one event term, and the record does not report overlap or event counts by term. It also does not give timing, duration, severity grades, attribution to treatment, exposure duration or methods for collecting events.

In general, seriousness and severity are distinct concepts: seriousness concerns regulatory or clinical consequences, while severity describes intensity. The registry does not supply enough detail to characterize the events beyond its serious-event classification and listed terms. These descriptive figures do not establish comparative risk or causation.

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

The registry record establishes that an open-label, single-arm Phase II study assessed intravenous BI 6727 (volasertib) in patients with locally advanced, metastatic or recurrent urothelial cancer after prior chemotherapy. Its primary endpoint was the percentage of participants with a complete or partial response according to RECIST 1.1, assessed from first drug administration until end of study, up to 2 years. The record also reports safety counts for the treated group.

The record does not report the primary response estimate or its 95% confidence interval. It therefore does not support a numerical statement about the frequency or precision of objective response. It also does not report results for the listed secondary outcomes. The listed enrollment of 50 is not a substitute for the number contributing to an endpoint, and the analysis population label is not explained.

Because there is no concurrent control group or randomized allocation, the design cannot provide a randomized comparison between BI 6727 and another treatment. Even if an outcome estimate were available, a single-group result would describe observed outcomes in that study population rather than isolate a causal treatment effect. Differences from other studies would require careful consideration of study populations, methods and follow-up.

The safety counts likewise describe events in the study group, not differences in risk between treatments. The record does not report enough information to assess exposure-adjusted risk, event timing, attribution or the reasons for the missing deaths value. Counts and term percentages should not be treated as proof of causation.

In general, trial results are interpreted alongside design, endpoint definitions, uncertainty, missing-data handling and the population studied. Here, important efficacy results and analysis details are absent from the registry record. The trial's documented question and design can be described, but the record alone does not establish the size or precision of an efficacy result or a comparative effect.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated endpoint and a reported estimate are both necessary for statistical interpretation. The registry defines objective response using CR or PR under RECIST 1.1, gives a percentage as the unit, identifies a 95% confidence interval, and states a follow-up window of up to 2 years. Those details clarify what the endpoint is intended to measure. Without the response estimate, denominator and interval, however, the result's magnitude and precision remain unavailable.

Its single-arm design also illustrates the distinction between describing an outcome and estimating a comparative effect. A response proportion in a treated group can be a useful descriptive quantity, but in general it does not provide a randomized contrast. That distinction is important when interpreting evidence from a Phase II study and when considering comparisons across separate studies.

The record also brings out the difference between outcome listings and reported analyses. It contains 24 outcome measures but zero analyses. A list of outcomes identifies areas of measurement, not a set of numerical findings or a complete statistical analysis plan. Without posted analyses, readers cannot examine estimates, uncertainty, missing-data decisions or multiplicity handling.

Finally, safety counts show why event summaries need context. Counts and term percentages describe what was recorded in the group, while a control group, exposure information and event-level detail would be needed for stronger comparative interpretation. The record documents useful design and endpoint information, yet leaves key inferential details unreported.

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 principal limitation for interpreting efficacy is that the registry record does not report the primary response result, its denominator or its confidence interval. The primary endpoint is defined, but its numerical finding and precision cannot be evaluated. The record also lists zero analyses, so no outcome-specific estimates or methods are available for review.

The single-arm, open-label design limits causal and comparative interpretation. There is no randomized control group, and the record does not report masking. It does not describe independent or blinded outcome assessment, imaging schedules, response confirmation procedures or detailed eligibility criteria. These omissions do not show that a procedure was absent; they mean it is not reported in the registry record.

The registry does not explain the TS analysis-population label or identify the primary endpoint denominator. It does not report participant flow, evaluability, missing assessments, protocol deviations or methods for handling missing data. The listed enrollment figure cannot resolve those questions.

Although 24 outcome measures are listed, multiplicity procedures and the relationship between primary and secondary analyses are not reported. Detailed methods for the listed survival outcomes, pharmacokinetic analyses and adverse-event collection are also not reported in the registry record.

The safety information is limited to group counts and selected serious adverse event terms. Deaths are not reported in the registry record, and event timing, duration, attribution, exposure and overlap are not described. These limits make the safety figures descriptive rather than comparative.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intravenous BI 6727 (Volasertib) in 2nd Line Treatment of Urothelial Cancer — NCT01023958.
• Registry record last updated 2017-11-22; status last verified 2017-10.
• Results first posted 2017-11-22.
• 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

The registry record describes NCT01023958 as a completed, open-label, single-arm Phase II trial sponsored by Boehringer Ingelheim. It evaluated intravenous BI 6727 (volasertib) in patients with locally advanced, metastatic or recurrent urothelial cancer after prior chemotherapy. Listed enrollment is 50; the study start date is 2009-11-19 and the primary completion date is 2011-09-19.

The primary endpoint was objective tumour response, defined as CR or PR according to RECIST 1.1, expressed as a percentage of participants over a period from first drug administration until end of study, up to 2 years. The response estimate and 95% confidence interval are not reported in the registry record. The record lists 24 outcome measures and zero analyses.

For safety, 13 participants were affected by serious adverse events and 49 by other adverse events among 50 at risk. The listed serious-event terms each have a reported percentage of 4.0%. Deaths are not reported in the registry record. The single-group design does not provide a randomized treatment comparison.