Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery (NCT02178241), a na phase 2 study. The primary outcome is Observed Overall Response Rate.

2. Clinical Question

This is a question about observed tumor response in a defined treatment group, rather than a direct comparison of two treatment strategies. A confirmed complete response requires disappearance of all target lesions. A partial response is defined as a decrease of at least 30% in the sum of the longest diameters of target lesions. The endpoint combines these response categories and uses eligible patients who began treatment as its denominator.

The trial enrolled 26 participants. That enrollment figure does not itself establish how many were eligible for the primary analysis or how many had evaluable response assessments. The registry description defines the endpoint denominator, but does not report the corresponding count or the response numerator. Consequently, the clinical question is clear, but the posted information does not give the numerical answer needed to describe the observed response rate or its precision.

3. Trial Design

This is a phase II, single-group trial of gemcitabine hydrochloride and eribulin mesylate. The registry record lists allocation as not applicable and masking as none. With one treatment group and no control arm, the design can describe outcomes observed among treated participants, but cannot estimate a randomized treatment contrast against another regimen or against no treatment.

The trial enrolled 26 participants. Its stated population was cisplatin-ineligible patients with advanced or unresectable urothelial carcinoma of the bladder. The listed conditions include metastatic and stage III or stage IV bladder, ureter, and urethral cancers. Further eligibility criteria and details about how participants were selected are not reported in the registry record.

Participants in the treatment group received gemcitabine hydrochloride intravenously over 30 minutes and eribulin mesylate intravenously over 2–5 minutes on days 1 and 8. Courses repeated every 21 days in the absence of disease progression or unacceptable toxicity. The record does not give additional information about dose levels, dose modifications, treatment duration, or the number of courses received.

The primary endpoint was observed overall response rate, assessed up to 36 months. Secondary outcomes listed in the record include progression-free survival, overall survival, and incidence of adverse events. Although four outcome measures are recorded, the names of only these three secondary outcomes are listed alongside the primary endpoint. Outcome estimates for the primary and secondary endpoints are not reported in the registry record.

The study is marked completed. The start date is 2014-12-11, and the primary completion date is 2019-03-18. These record details describe the study’s administrative timeline; they do not supply a response estimate or establish how complete the outcome follow-up was. The protocol’s sample-size justification, planned analysis procedures, and any interim analyses 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

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 Observed Overall Response Rate, measured over Up to 36 months.

The primary endpoint is observed overall response rate. It is the number of eligible patients who began treatment and experienced a confirmed complete response or partial response, divided by the number of eligible patients who began treatment. Complete response means disappearance of all target lesions. Partial response means a decrease of at least 30% in the sum of the longest diameters of target lesions. The assessment is described as following RECIST v1.1 for target lesions and using MRI, with a timeframe of up to 36 months.

A response-rate endpoint provides a compact description of the proportion of a treatment group reaching specified tumor-response criteria. It can be useful in a phase II study because it focuses on whether participants meet a prespecified response definition, rather than on a direct comparison with a control group. The use of defined lesion criteria also makes the response categories more explicit than an informal judgment of improvement.

General statistical context: a response proportion is an estimate based on the participants included in its denominator. Its precision depends in part on the number of participants assessed and the number who meet the response definition. A confidence interval communicates uncertainty around that estimate; it is not a guarantee that the true response proportion lies within a particular interval.

The registry record names a 95% confidence interval as the endpoint’s dispersion measure, but does not report the observed response-rate estimate, the interval limits, or the counts used to calculate them. The endpoint definition therefore describes what was intended to be measured, but the posted information does not establish the magnitude or precision of the observed response rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response-rate estimate represent?

For a binary endpoint such as confirmed response, each participant included in the analysis is classified according to whether the defined event occurred. The response rate is the proportion classified as having a complete or partial response. In this trial, the endpoint definition says to use eligible patients who began treatment as the denominator. That denominator matters: an estimate based on all enrolled participants can differ from one based on those eligible, treated, or assessed, especially if some participants do not contribute an evaluable response.

The registry record does not report the response numerator or denominator, so no rate can be stated from the available outcome information. It also does not report the limits of the stated 95% confidence interval. A confidence interval expresses sampling uncertainty around an estimate under the method used to calculate it. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty; neither the interval nor the estimate substitutes for the design limitations of a single-group study.

What does the single-group design allow?

General statistical context: a single-group study describes outcomes within the group that received the treatment. Without a concurrent randomized control group, it does not estimate a treatment difference by random assignment. Changes over time or observed responses can also reflect features of participant selection, the natural course of disease, other care, or measurement. These possibilities do not negate the descriptive value of the study, but they limit causal and comparative interpretations.

Allocation is listed as not applicable, masking as none, and the model as single group. Those details mean that a like-for-like randomized comparison is not available in this record. A comparison with a result from a separate study would not have the protections of a concurrent randomized comparison and could be affected by differences in populations, assessment, or follow-up. The record does not describe such a comparison as its primary analysis.

How should the endpoint definition be read?

The endpoint follows RECIST v1.1 criteria for target lesions. It combines complete response, defined as disappearance of all target lesions, with partial response, defined as a decrease of at least 30% in the sum of the longest diameters of target lesions. A participant must have a confirmed complete or partial response to count in the numerator. The timeframe is up to 36 months. The record says the assessment is by MRI, but additional assessment procedures and confirmation details are not reported in the registry record.

Combining complete and partial responses produces one overall response endpoint, but it does not show the separate frequency of each response category. Those category-specific counts are not reported. Nor does an overall response proportion describe how long a response lasted; duration of response is not among the listed outcomes in the registry record.

What do the safety figures describe?

General statistical context: adverse-event incidence figures are descriptive counts or proportions within a defined group and observation period. Their interpretation depends on how events were defined, collected, and attributed, as well as on the number of participants observed and the time each participant was followed. The record lists participants at risk and affected for serious and other adverse events, but the detailed collection and attribution procedures are not reported in the registry record.

The serious adverse-event terms are accompanied by percentages. Those percentages are registry-listed descriptions and should not be treated as a comparison with another treatment, a measure of causal risk, or a complete account of all adverse events. The record also lists deaths, but the information available does not specify whether those deaths were treatment-related, the circumstances, or the timing. A death count alone cannot establish causation.

What can be said about analysis planning?

The protocol’s statistical analysis plan, sample-size justification, interim analyses, and handling of missing outcome data are not reported in the registry record. The record includes a planning illustration based on a stated effect fraction and assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is not the trial’s own design justification, and it does not turn this single-group study into a two-arm comparison. Any sample-size values in that context are planning illustrations, not observed power.

General statistical context: a planned sample size concerns the information a design aims to collect under specified assumptions. Observed power is not a substitute for reporting an estimate and its uncertainty. For interpreting a completed study, the outcome estimate, its confidence interval, analysis population, and completeness of follow-up are more informative. The registry record does not provide the primary result or the analysis details needed to evaluate those features.

How should absent analysis details be handled?

The record lists no analyses in the information available for this analysis. It does not report adjustment methods, subgroup analyses, sensitivity analyses, or the handling of participants with missing assessments. These details should not be inferred from the endpoint definition or from the phase of the study. Without them, it is not possible to assess whether the posted endpoint estimate, if reported elsewhere, would reflect all eligible participants who began treatment or a narrower evaluable group.

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("Treatment (Eribulin Mesylate and Gemcitabine Hydro")
n      <- c(24)
events <- c(12)
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  Treatment (Eribulin Mesylate and Gemcitabine Hydro  24  12  50.0  29.1  70.9  31.4  68.6  31.3  68.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists observed overall response rate as the primary outcome and names progression-free survival, overall survival, and incidence of adverse events as secondary outcomes. It records four outcome measures in total, but the available information does not list a fourth outcome by name. It does not report a multiplicity procedure, a hierarchy among secondary outcomes, or an adjustment to significance thresholds. Those statistical-plan details are not reported in the registry record.

General statistical context: when several outcomes or analyses are considered, the chance of at least one apparently unusual result can increase if each is assessed separately. A prespecified hierarchy or multiplicity adjustment can help define how findings should be interpreted across multiple tests. The absence of information about such procedures does not prove that none were used; it means their use is not reported in the registry record.

The record does not provide the primary response numerator or denominator, the confidence interval limits, or numerical results for the listed secondary outcomes. It also does not describe the analysis populations for these endpoints beyond the primary endpoint’s definition as eligible patients who began treatment. The number of participants with missing response assessments, reasons for missingness, and any method used to handle missing data are not reported in the registry record.

These omissions limit assessment of how the analysis population was formed and whether incomplete assessments could affect the reported estimate. General statistical context: missing outcome information can affect interpretation when the likelihood of missingness is related to participant characteristics or outcomes. Without details about missingness and analysis rules, its direction and impact cannot be determined. No missing-data assumptions should be attributed to the study based on the registry record alone.

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: white blood cell decreased (16.7%), colitis (12.5%), sepsis (12.5%), urinary tract infection (12.5%), dehydration (12.5%).

The registry record lists 24 participants at risk for serious adverse events and 16 affected. For other adverse events, it lists 24 at risk and 24 affected. It also records 20 deaths. These are counts as posted for the treatment group; the record details do not specify timing, duration of observation, event attribution, or the circumstances of the deaths.

The listed serious adverse-event terms and percentages are White blood cell decreased, 16.7%; Colitis, 12.5%; Sepsis, 12.5%; Urinary tract infection, 12.5%; Dehydration, 12.5%; and Febrile neutropenia, 8.3%. They are descriptive entries, not a comparison between treatment groups. The percentages should be read as reported, without assuming that each term represents a distinct participant or that the terms account for every serious event.

General statistical context: adverse-event counts describe events recorded under the study’s collection procedures. They do not, on their own, establish that treatment caused an event. The registry record does not provide enough detail to determine relatedness, severity grading beyond the serious-event classification, or whether events overlapped within participants. The death count likewise does not establish treatment attribution. These safety figures should therefore be read as descriptive registry information rather than as causal estimates.

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

The record documents a completed phase II, single-group study of gemcitabine hydrochloride with eribulin mesylate in cisplatin-ineligible patients with advanced or unresectable urothelial carcinoma. It gives the treatment schedule and defines the primary endpoint as the proportion of eligible patients who began treatment and experienced a confirmed complete or partial response. It also lists selected safety counts and serious adverse-event terms.

The record does not report the observed response-rate estimate or its 95% confidence interval. It therefore does not allow a numerical statement about the response proportion or its precision. The enrollment of 26 participants is not a substitute for the endpoint denominator, because the response definition uses eligible patients who began treatment and the corresponding count is not reported. The record also does not give numerical results for the listed progression-free survival and overall survival outcomes.

The trial’s single-group design means that any observed outcome would describe participants who received this regimen, not a randomized difference against another treatment. The registry information does not support a causal conclusion that the regimen produced a particular outcome or a comparative conclusion about how it performs relative to another approach. Such conclusions would require evidence beyond the outcome details available in this record.

The safety entries are also descriptive. The listed counts and percentages do not establish that treatment caused an adverse event or death, and the available details do not show the timing or attribution of deaths. At the same time, the absence of a reported primary efficacy estimate should not be interpreted as evidence of no response, and the listed adverse events should not be treated as a complete account of clinical risk.

In short, the registry record supports understanding of the study question, design, endpoint definition, treatment schedule, and selected safety reporting. It does not provide the efficacy estimates or analysis details needed to characterize the primary result, its uncertainty, or comparative effects.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between an endpoint being defined and its result being reported. The record gives a clear response criterion, including the target-lesion rules for complete and partial response, and identifies the denominator intended for the overall response rate. Yet the observed rate and its confidence interval are not reported in the registry record. Without those values, readers cannot assess the magnitude or precision of the primary outcome.

It also shows why study design affects the question that data can answer. A single-group phase II study can describe outcomes in participants who received a regimen. It does not provide a randomized treatment contrast, so any outcomes cannot by themselves establish comparative effects. Recognizing that distinction prevents a descriptive result from being read as a controlled estimate.

The enrollment count and endpoint population definition also highlight the importance of analysis denominators. Enrollment is not automatically the number eligible, treated, or evaluable for a response assessment. A transparent report would make those counts and the handling of incomplete assessments clear, allowing readers to understand which participants contributed to the estimate.

Finally, the safety information demonstrates the value and limits of registry-level counts. Counts, percentages, and event terms can help describe what was recorded, while questions about causation, timing, overlap, and completeness require further detail. Statistical interpretation depends not only on the choice of endpoint, but also on reporting the estimates, uncertainty, populations, and methods needed to understand them.

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 primary limitation for interpreting efficacy is that the observed overall response rate and its 95% confidence interval are not reported in the registry record. The response numerator and the number of eligible participants who began treatment are also not reported. Although enrollment was 26, that total does not establish the primary endpoint denominator or the number with evaluable assessments.

The single-group design has no randomized control arm. It can describe outcomes in the treatment group but does not estimate a controlled treatment effect. The record lists allocation as not applicable and masking as none. It does not report further information on participant selection, eligibility criteria, or procedures that would allow a fuller assessment of how representative the enrolled group was.

Several details needed to evaluate the endpoint are not reported in the registry record, including response counts by category, assessment completeness, confirmation procedures beyond the stated criteria, and duration of response. Numerical results for progression-free survival and overall survival are also not reported in the information available for this analysis.

The registry record does not describe the statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, analysis populations for secondary outcomes, or handling of missing data. These absences limit assessment of prespecification and robustness; they do not establish what procedures were or were not used outside the record.

Safety interpretation is limited by the absence of detail on event timing, attribution, collection procedures, overlap among event terms, and the circumstances of the listed deaths. The reported counts and percentages are descriptive and do not support causal or comparative conclusions. These trial-specific reporting and design limitations should be kept in view when interpreting its outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gemcitabine Hydrochloride and Eribulin Mesylate in Treating Patients With Bladder Cancer That is Advanced or Cannot Be Removed by Surgery — NCT02178241.
• Registry record last updated 2019-12-16; status last verified 2019-11.
• Results first posted 2019-12-16.
• 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

NCT02178241 is a completed phase II, single-group trial sponsored by the National Cancer Institute (NCI). It enrolled 26 participants and studied gemcitabine hydrochloride with eribulin mesylate in cisplatin-ineligible patients with advanced or unresectable urothelial carcinoma. Treatment was administered intravenously on days 1 and 8, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity.

The primary endpoint was observed overall response rate, assessed up to 36 months using RECIST v1.1 criteria for target lesions. The observed rate, its 95% confidence interval, and the analysis denominator are not reported in the registry record. Listed secondary outcomes were progression-free survival, overall survival, and incidence of adverse events, without numerical outcome estimates in the information.

The safety record lists serious and other adverse-event counts, 20 deaths, and selected serious adverse-event terms with percentages. The design has no comparator arm, so the record provides no randomized treatment contrast.