Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction (NCT00365157), a na phase 1, phase 2 study. The primary outcome is Number of Subjects With Overall Response.

2. Clinical Question

The study addresses treatment in a population for whom kidney function is relevant to chemotherapy exposure and effects. Its phase I component separates participants into moderate and severe renal dysfunction dose-level groups. The phase II component describes cohorts by treatment setting and prior exposure: first-line treatment, platinum-refractory tubulin-naïve disease, and platinum-refractory tubulin-exposed disease. These categories identify distinct clinical contexts; they do not create a randomized comparison.

The clinical question is therefore about observed response and other outcomes among participants receiving eribulin mesylate in the specified cohorts, not about a treatment effect relative to an untreated or active control group. The registry also lists progression-free survival, overall survival, and adverse events as secondary outcomes. The result entries for those outcomes are not reported in the registry record.

3. Trial Design

This is a phase I/II interventional study sponsored by the National Cancer Institute. The registry lists a planned enrollment of 168 and identifies the design as single-group. Allocation is recorded as NA, and masking is listed as none. Thus, neither random allocation nor blinding is described, and the registry does not identify a concurrent control arm.

The phase I description includes dose-level groups for participants with moderate renal dysfunction and for participants with severe renal dysfunction. In each renal-function category, the listed dose levels are 0.7 mg/m²/Week, 1.0 mg/m²/Week, and 1.4 mg/m²/Week. The phase II description gives three cohorts: first-line treatment; platinum refractory, tubulin-naïve; and platinum refractory, tubulin-exposed. The registry presents these as treatment cohorts, not as randomized arms designed for a direct causal comparison.

Participants in the treatment arm receive eribulin mesylate intravenously over 1-2 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. The registry also lists laboratory biomarker analysis and a pharmacological study as interventions.

The trial began on 2006-10-23. The record lists a primary completion date of 2025-07-09 and a status of active, not recruiting. These registry entries describe study conduct and status; they do not establish that every outcome has been analyzed or posted. Although the record identifies 10 outcome measures, it has no analysis entries. The protocol’s sample-size justification, planned interim analyses, and full statistical analysis plan 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.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 8 tubulin-treated patients were accrued to the dose-finding Phase I portion of this 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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Overall Response, measured over Up to 6 months.

The primary endpoint is the number of participants with an overall response, with the assessment timeframe listed as up to 6 months. It is a participant count rather than a continuous measurement. The registry defines overall response as complete response plus partial response according to RECIST v1.1.

Under the definition in the record, complete response requires disappearance of all target lesions and all non-target lesions, along with normalization of tumor marker level. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. The endpoint combines these response categories into a single measure of tumor response during the stated timeframe.

Response is commonly used in oncology studies because it describes whether measurable disease meets prespecified criteria for shrinkage or disappearance. As a general statistical point, a participant count is easiest to interpret alongside the number assessed and an uncertainty interval, since the same count can imply different levels of precision in different-sized groups. Such an interval and the primary response count are not reported in the registry record.

Because there is no randomized comparator, the endpoint can describe responses observed among treated participants but cannot, by itself, distinguish treatment-associated change from the natural course of disease or other influences. The registry does not provide enough result information to evaluate the magnitude or precision of response in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a count of participants with an event: in this case, participants meeting the registry definition of overall response. For a binary endpoint, each participant is classified as meeting or not meeting the response definition for the relevant assessment. A useful summary requires both the number meeting the endpoint and the number assessed. The registry record does not report those response results, so no response proportion can be interpreted from the record.

As a general statistical concept, uncertainty in a binary outcome depends on the amount of information in the data and on the observed event frequency. A confidence interval expresses uncertainty around an estimate under a stated statistical method. It is not a guarantee, and its interpretation depends on the assumptions and analysis population used. The registry record does not report a response estimate, confidence interval, or statistical method for the primary endpoint.

The study is described as single-group, with no masking and allocation recorded as NA. In a randomized comparative trial, random assignment is intended to make the groups comparable on average, including for characteristics that are not measured. Here, the listed cohorts are not randomized controls. A response count within a cohort can describe what was observed in that cohort, but a difference between cohorts would not automatically establish that treatment dose or cohort membership caused the difference. The cohorts may differ in disease setting, prior treatment, or renal dysfunction, and the record does not report a comparative adjustment strategy.

The primary endpoint uses RECIST v1.1 definitions. Complete response and partial response are distinct categories, combined in the registry’s overall response definition. Such criteria standardize how tumor response is classified, but the record’s endpoint definition alone is not a result. To interpret results, readers would need the actual response counts, the assessment denominator, and information about how participants without evaluable assessments were handled. Those details are not reported in the registry record.

The study includes phase I and phase II components. The phase I groups are organized by renal dysfunction severity and dose level. The phase II cohorts are organized by treatment context and prior exposure. These structures have different descriptive purposes, but the registry does not report the dose-selection rules, escalation or stopping rules, or the statistical decision criteria used for the phase I component. The statistical plans for the phase II cohorts are also not reported.

The record lists progression-free survival and overall survival as secondary outcomes. In general, time-to-event outcomes measure time until a defined event, while accounting for participants whose event has not been observed by the analysis cutoff. Interpretation depends on definitions of the event and time origin, duration of follow-up, censoring rules, and the analysis method. The registry record does not provide those analysis details or the relevant outcome estimates. The record lists progression-free survival twice; it does not explain whether the entries represent distinct analyses or duplicate outcome listings.

Safety outcomes are also distinct from efficacy outcomes. Counts of participants with adverse events are not interchangeable with counts of events, because one participant may experience more than one event. The registry lists participants at risk, participants affected, and deaths for the groups, but the details given do not establish the attribution of deaths or provide exposure-adjusted safety rates. For the serious-event terms, the listed percentages should be interpreted with attention to their denominator; that denominator definition is not reported in the registry record.

General statistical planning often uses a target significance level and power to describe a proposed study’s ability to detect a specified effect under assumptions. A sample-size calculation is not a measure of how much power a completed trial actually achieved. The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a stated fraction of the observed effect. Time-to-event illustrations use a total event count; other illustrations use participants per arm. These are planning conventions, not descriptions of the recorded single-group trial design, and the registry’s own sample-size justification is not reported.

When a trial includes multiple outcomes, cohorts, or subgroup analyses, multiplicity can increase the chance of at least one apparently unusual result if many comparisons are interpreted without accounting for the number of tests. A prespecified hierarchy or multiplicity adjustment can help control that issue. The registry record does not report such a plan, nor does it report the number of statistical tests actually performed. Its analysis-entry count is 0.

Missing outcome data can also affect interpretation. If participants with missing assessments differ systematically from those assessed, a complete-case summary may not represent the full study population. Methods such as imputation or sensitivity analyses depend on assumptions about why data are missing. The registry record does not report missing-data counts, the handling of missing response assessments, or the analysis population used for any endpoint. These omissions prevent assessment of the robustness of a reported estimate, and the record contains no posted primary estimate to assess.

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("Dose Level 1 - Moderate Renal Dysfunction, 0.7 mg/", "Dose Level 2 - Moderate Renal Dysfunction, 1.0 mg/", "Dose Level 3 - Moderate Renal Dysfunction, 1.4 mg/", "Dose Level 1 - Severe Renal Dysfunction, 0.7 mg/m²", "Dose Level 2 - Severe Renal Dysfunction, 1.0 mg/m²", "Dose Level 3 - Severe Renal Dysfunction, 1.4 mg/m²")
n      <- c(2, 3, 6, 3, 3, 6)
events <- c(0, 1, 3, 0, 1, 2)
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  Dose Level 1 - Moderate Renal Dysfunction, 0.7 mg/  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Dose Level 2 - Moderate Renal Dysfunction, 1.0 mg/  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Dose Level 3 - Moderate Renal Dysfunction, 1.4 mg/  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Dose Level 1 - Severe Renal Dysfunction, 0.7 mg/m²  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Dose Level 2 - Severe Renal Dysfunction, 1.0 mg/m²  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6
ARM  Dose Level 3 - Severe Renal Dysfunction, 1.4 mg/m²  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and names overall response as the primary endpoint, with progression-free survival, overall survival, and adverse events among the secondary outcomes. It does not report a multiplicity strategy, such as an ordered testing hierarchy or an adjustment for multiple statistical comparisons. Without a reported plan, it is not possible to determine how the investigators intended to distinguish confirmatory findings from exploratory ones across outcomes or cohorts.

The record has 0 analysis entries. The result of the primary response endpoint and analyses of the secondary outcomes are not reported in the registry record. The registry also does not report the analysis populations, the number assessed for each outcome, or whether analyses followed an intention-to-treat, treated, or evaluable-participant definition.

Missing-data methods are not reported in the registry record. The record does not state how missing tumor assessments, withdrawals, or incomplete follow-up were handled. This matters because exclusions or assumptions about missing observations can change the interpretation of response and time-to-event outcomes. No sensitivity analysis for missing data is described.

The protocol’s statistical analysis plan, planned interim analyses, sample-size justification, and detailed endpoint-analysis specifications are not reported in the registry record. Accordingly, the listed outcome names and definitions alone do not establish which analyses were prespecified or how the reported results, if any, were selected.

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: fatigue (66.7%), muscle weakness (66.7%), urinary tract infection (50.0%), lymphocytopenia (50.0%), atrial fibrillation (33.3%).

The serious adverse-event entries are organized by phase I dose-level group and phase II cohort. Each group reports participants at risk and participants affected by serious adverse events. For example, the phase I moderate renal dysfunction groups list 1 of 2, 2 of 3, and 2 of 6 participants affected, respectively. The severe renal dysfunction groups list 1 of 3, 3 of 3, and 5 of 6. In phase II, the first-line cohort lists 19 of 42; the platinum-refractory tubulin-naïve cohort lists 44 of 58; and the platinum-refractory tubulin-exposed cohort lists 24 of 45.

These counts should be read within their own group and alongside the at-risk denominator. The cohorts differ in size and clinical definition, and the registry does not designate them as randomized safety comparators. The reported counts therefore do not establish a comparative treatment effect or a dose-related pattern.

The record also lists participants with other adverse events and death counts for each group. A death count does not, on its own, establish that deaths were caused by treatment. The registry information described does not report that attribution. Serious terms listed include fatigue, muscle weakness, urinary tract infection, lymphocytopenia, atrial fibrillation, and atrial flutter, with percentages attached to each term. The denominator basis for those percentages is not reported in the registry record, so they should not be treated as directly comparable risks without that context.

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

The registry record establishes that a phase I/II, single-group study of eribulin mesylate was conducted in people with urothelial cancer and kidney dysfunction, with phase I groups organized by renal dysfunction and dose level and phase II cohorts organized by treatment context. It also specifies a primary response endpoint and lists secondary survival and adverse-event outcomes.

It does not, however, report the primary response count or an analysis of that endpoint. It also does not report estimates for progression-free survival or overall survival. The record therefore does not support a conclusion about the frequency or precision of response, or about the results of those secondary outcomes. A defined endpoint is not evidence of a particular outcome.

The safety entries describe participants with serious and other adverse events and deaths in each listed group. They provide descriptive counts, not a randomized comparison. The counts cannot establish whether one dose level or cohort has greater risk than another, especially because the groups are not presented as like-for-like controls and the record does not describe adjustment for differences between them. Death counts alone do not establish treatment attribution.

More generally, a single-group study can document observations among treated participants, but cannot by itself show what would have happened to those same participants under a different treatment or without treatment. A controlled comparison is needed to estimate a relative treatment effect, and randomization can help address confounding. No such randomized control comparison is described in the registry record.

The record’s enrollment figure of 168 is not an outcome denominator, and should not be used as though all enrolled participants contributed data to every endpoint. The analyzed population, outcome-specific denominators, missing-data handling, and uncertainty estimates are not reported. The record supports a description of the design and posted safety counts, but not a firm inference about efficacy, comparative safety, or the precision of the primary endpoint.

14. Why This Trial Matters Statistically

This study raises a statistical design issue that is especially important when treatment is studied in a population defined by kidney dysfunction: dose-level groups and clinical cohorts can differ in meaningful ways. Separating groups by renal dysfunction severity, dose, treatment setting, and prior exposure helps describe the study structure, but those distinctions also make direct comparisons difficult when allocation is not randomized.

The phase I and phase II components serve different roles within the study design. The phase I groups are organized around renal dysfunction and dose level, while the phase II cohorts reflect treatment context. Interpreting any differences between these groups would require clear prespecified objectives, analysis methods, denominators, and uncertainty estimates. Those statistical details are not reported in the registry record.

The study also illustrates why endpoint definitions and endpoint results must be distinguished. The record defines overall response using RECIST v1.1 and names a timeframe of up to 6 months, but does not post the response count or its analysis. A precise endpoint definition makes an outcome reproducible in principle; it does not tell readers what was observed or how uncertain the estimate is.

Finally, the absence of analysis entries and detailed information about multiplicity, missing data, and analysis populations limits the strength of statistical interpretation. These are not merely reporting details: they determine which participants and outcomes contribute to an estimate, and how much confidence readers can place in it. The registry record documents important design and safety information, while leaving the primary efficacy result and key analytical context unavailable.

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 does not report the primary endpoint result, any response denominator, or an uncertainty interval. It lists 10 outcome measures but has 0 analysis entries. Results for progression-free survival and overall survival are also not reported in the registry record. This leaves the main efficacy questions unanswered by the posted information.

The study is single-group, unmasked, and has allocation recorded as NA. There is no randomized control group, so the design cannot support a like-for-like estimate of treatment effect versus a comparator. Comparisons across the renal dysfunction dose levels or phase II cohorts would be vulnerable to differences in participant characteristics and treatment context.

The registry does not report its statistical analysis plan, sample-size justification, planned interim analyses, analysis populations, or missing-data methods. It also does not describe how the duplicated progression-free survival listing should be interpreted. Without these details, it is not possible to assess prespecification, handling of incomplete assessments, or the intended treatment of multiple outcomes.

The serious adverse-event entries give group-level counts, but the record does not provide the denominator basis for percentages attached to serious event terms or establish the attribution of deaths. Event counts should therefore be interpreted descriptively. The registry status is active, not recruiting, and a primary completion date is listed, but those administrative fields do not replace posted outcome analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction — NCT00365157.
• Registry record last updated 2026-10-28; status last verified 2026-07.
• Results first posted 2026-09-09.
• 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

NCT00365157 is a phase I/II, single-group study sponsored by the National Cancer Institute. It studies eribulin mesylate in locally advanced or metastatic urothelial cancer with kidney dysfunction. The registry lists planned enrollment of 168, no masking, and allocation as NA. Treatment is described as intravenous eribulin mesylate on days 1 and 8, with cycles repeating every 21 days if there is no disease progression or unacceptable toxicity.

The primary endpoint is the number of participants with overall response under RECIST v1.1, assessed up to 6 months. Secondary outcomes include progression-free survival, overall survival, and adverse events. The record lists phase I renal dysfunction and dose-level groups and three phase II cohorts. It reports serious and other adverse-event counts by group, but no primary response result or analysis of the listed efficacy outcomes. The registry lists the status as active, not recruiting, and the primary completion date as 2025-07-09.