Gemzar, Cisp, Sunitinib Urothelial Ca: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemzar, Cisp, Sunitinib Urothelial Ca (NCT00821327), a na phase 2 study. The primary outcome is Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib..

2. Clinical Question

The trial's stated primary objective was to evaluate objective response rate (ORR) for the three-drug combination in advanced or metastatic urothelial carcinoma. Complete response was defined as disappearance of all target lesions. Partial response was defined as at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference.

This is a question about the frequency of responses in the treated study group, not a direct comparison of the combination with another treatment. The registry describes a nonrandomized, single-group Phase II trial. Consequently, an observed response rate, if reported, would describe outcomes in the trial population; by itself it would not estimate a treatment difference against an untreated or alternative-treatment group.

The recorded enrollment was 36. That figure describes enrollment, whereas the endpoint population is specified more narrowly by eligibility, protocol-specified efficacy analysis requirements, and receipt of at least 1 dose. The registry record does not give the number meeting those endpoint-population criteria or report the response count. As a result, the recorded objective and its definitions can be described, but the observed response frequency cannot be assessed from this record.

3. Trial Design

This was a completed Phase II study, recorded as a single-group, nonrandomized trial with no masking. The registry lists one study arm: gemcitabine, cisplatin, and sunitinib for advanced or metastatic urothelial carcinoma. Enrollment was 36. The listed sponsor was US Oncology Research. The recorded study start was 2008-08, and the primary completion date was 2012-08.

The design addresses outcomes in a treated group rather than a contrast between randomized groups. There is no separate comparator arm in the registry record. The record also does not describe allocation beyond marking it as not applicable, which is consistent with the single-group designation. Because there is no concurrent control group, the design does not provide a randomized estimate of how outcomes differ from those under another treatment.

The primary objective was to evaluate objective response rate, defined as complete response plus partial response. The recorded timeframe is 2 years. The record specifies that the response analysis population comprises eligible patients who meet protocol-specified efficacy analysis requirements and received at least 1 dose of study drug. The protocol-specific requirements themselves are not reported in the registry record.

Progression-free survival and OS are listed as secondary outcomes. The record does not provide results for these outcomes, their definitions, or their analysis methods. It lists 3 outcome measures, but statistical analyses are not listed in the registry record. The completion status indicates that the study is marked completed; it does not, by itself, supply endpoint results or establish that all planned analyses were posted.

The trial record does not report the treatment schedule, dose levels, treatment duration, eligibility details beyond the primary endpoint population description, or the basis for its enrollment target. It also does not report whether interim analyses were planned or conducted. Those omissions limit reconstruction of the operational design and prevent assessment of the rationale behind the design choices. No details about randomization or masking should be inferred from a different trial design: the registry identifies this study as nonrandomized, single-group, and unmasked.

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: All eligible patients who meet the protocol-specified efficacy analyses requirements and who have received at least 1 dose of study drug.

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 Objective Response Rate (ORR, CR+PR) in Patients With Advanced/Metastatic UC Treated With the Combination of Gemcitabine, Cisplatin, and Sunitinib., measured over 2 years.

The primary endpoint is objective response rate (ORR), defined as the percentage of participants with a complete or partial response. Complete response means disappearance of all target lesions. Partial response means at least a 30% decrease in the sum of the longest diameters of target lesions, compared with the baseline sum. The endpoint is recorded with a 95% confidence interval and a timeframe of 2 years.

ORR is a binary-outcome summary: each eligible patient contributes a response classification, and the response rate describes the fraction classified as having a complete or partial response. As a general statistical matter, a binary endpoint can summarize whether a predefined event occurred, but its interpretation depends on how response was assessed, which patients were included, and how missing or unevaluable assessments were handled. The registry gives the target-lesion definitions and an analysis-population description, but it does not report the observed response count, denominator, or handling of unevaluable assessments.

A confidence interval expresses uncertainty around an estimated response rate. Its width depends in part on the amount of information available and on the observed event frequency. The registry identifies a 95% confidence interval as the dispersion measure, but it does not state the method used to construct it or report its bounds. Thus, the endpoint definition and intended precision measure are available, while the estimate and its uncertainty are not reported in the registry record.

ORR is the stated primary outcome, with progression-free survival and OS listed as secondary outcomes. The record does not provide the results for any of these endpoints. The response endpoint therefore defines the question the study intended to address, but the registry entry does not permit evaluation of the observed response frequency.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint summarize?

ORR is a binary endpoint because each person considered in the analysis is classified according to whether a complete or partial response was recorded. The percentage is intended to express the proportion of the analysis population meeting that response definition. As a general statistical explanation, such an estimate depends on both the number classified as responders and the number included in the analysis. The registry record does not report either quantity for this endpoint, so the percentage cannot be reconstructed from the available entry.

The response categories are defined using target-lesion assessments. Complete response is disappearance of all target lesions; partial response is at least a 30% decrease in the sum of their longest diameters relative to the baseline sum. These definitions set a rule for classifying response. The registry does not report further assessment procedures, such as how assessments were scheduled or reviewed, or how borderline, missing, or unevaluable assessments were classified.

What does the confidence interval add?

The primary outcome is specified with a 95% confidence interval. In general, a confidence interval describes uncertainty in an estimate under a particular statistical method and its assumptions. It is not a guarantee that the true value lies within the particular interval, and it does not by itself determine clinical importance. A narrower interval generally indicates greater precision than a wider interval, while the interval's location conveys the range of values compatible with the data and method.

The interval method is not reported in the registry record. Neither the point estimate nor the interval limits are reported, so no conclusion can be drawn about the precision of the intended primary result. Different interval methods can behave differently, particularly when binary outcomes are based on limited information or event frequencies near the ends of the possible range. This is a general methodological consideration, not a claim about the unreported ORR in this trial.

Why does the analysis population matter?

The endpoint population is described as all eligible patients who meet protocol-specified efficacy analysis requirements and have received at least 1 dose of study drug. This definition indicates that the intended denominator may depend on eligibility and efficacy criteria, not only on enrollment. The record does not state how many participants met that definition, nor does it provide a participant flow or details of exclusions. The enrollment figure of 36 should therefore not be substituted for an endpoint denominator without supporting information.

As a general principle, defining the analysis population before interpreting a percentage is essential: the same response count can yield different estimates under different denominators. Missing assessments can also affect interpretation if participants without evaluable outcomes are omitted, counted as nonresponders, or handled by another rule. The registry record does not report the missing-data rule or whether any primary endpoint data were missing. No such approach should be assumed.

What can be inferred from the design?

This study is recorded as a single-group, nonrandomized Phase II trial with no masking. The primary endpoint is therefore a within-group response frequency, not a comparison of randomized treatment groups. General statistical interpretation distinguishes a descriptive response proportion from a causal treatment contrast: estimating a contrast requires a comparison strategy and assumptions about how groups relate. This registry record does not describe a comparator group or a randomized contrast.

The record lists progression-free survival and OS as secondary outcomes. These are time-to-event outcomes in general, but the registry entry does not report their endpoint definitions, analysis results, censoring rules, or statistical methods. It would be inappropriate to infer such details from the names alone. The record lists 3 outcome measures and no statistical analyses, so it does not support a reconstruction of the analysis plan or a review of the secondary-outcome estimates.

What are the planning illustrations?

The study's sample-size justification and original statistical design are not reported in the registry record. Any planning illustration based on an observed effect is a hypothetical calculation, not a description of the study's original enrollment rationale and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the illustration concerns the total number of events; for other outcomes, it concerns participants per arm.

Those assumptions do not make the underlying trial a two-arm study. The registry describes one study arm, and the illustration's equal-allocation assumption is for hypothetical planning. A planning estimate answers a conditional question about a future design under stated assumptions; it does not establish the probability that this completed study detected an effect. The registry record does not report an original target effect, sample-size calculation, or prespecified power target.

More generally, a sample-size calculation depends on a chosen design, endpoint, target effect, variability or event assumptions, error rates, and analysis method. If those inputs differ from what is ultimately observed, the realized precision can differ from the planning expectation. No recalculated analysis of the primary endpoint can be made from this record because the response estimate and its analysis denominator are absent. Accordingly, the statistical methods that can be described are the intended endpoint type and confidence-interval measure; the actual estimation procedure and analysis plan 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("Study Arm: Advanced/Metastatic UC")
n      <- c(33)
events <- c(16)
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  Study Arm: Advanced/Metastatic UC  33  16  48.5  30.8  66.5  32.5  64.8  32.4  64.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies ORR as the primary outcome and lists progression-free survival and OS as secondary outcomes. It also records 3 outcome measures. However, statistical analyses are not listed, and the record does not describe a multiplicity plan. It is therefore not reported in the registry record whether the secondary outcomes were treated as confirmatory or exploratory, whether testing was adjusted across outcomes, or whether any hierarchy or decision rule was specified.

As a general statistical matter, assessing multiple outcomes can increase the chance of at least one apparently unusual result if each is tested separately. A prespecified multiplicity strategy can define how evidence is interpreted across outcomes. Since no analysis results or strategy are recorded, it is not possible to assess whether multiplicity was addressed or how the endpoint findings should be interpreted jointly. This is an information gap, not evidence that a particular strategy was or was not used.

The primary endpoint population requires eligibility, protocol-specified efficacy analysis criteria, and receipt of at least 1 dose. The record does not report the number meeting those requirements, the number with an evaluable response, or any missing-data handling rule. It is not reported in the registry record whether participants without an evaluable response were excluded, classified in another way, or addressed through a sensitivity analysis. The endpoint result and its denominator are also absent, so the practical impact of missing data cannot be assessed.

The record does not give participant flow, reasons for exclusions or withdrawal, or analysis populations for the secondary outcomes. The protocol-specific efficacy requirements and any interim analyses are not reported in the registry record. Without these details, a reader cannot establish whether the reported enrollment and the intended primary analysis population correspond, or whether analyses followed a prespecified plan. No assumptions about missingness, analysis populations, or multiplicity should be substituted for these unreported details.

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: anemia (3.0%), blood pressure increased (3.0%), cellulitis (3.0%), hemoglobin decreased (3.0%), lymphadenopathy thoracic (3.0%).

The registry lists a Study Arm: Advanced/Metastatic UC safety group. For serious adverse events, it records 33 at risk and 7 affected. For other adverse events, it records 33 at risk and 32 affected. These are the registry's reported counts; the entry does not provide a safety analysis narrative that clarifies event-level counting, repeated events, or the relationship between the serious and other adverse-event categories. The figures should not be added together or treated as a count of unique people.

The serious adverse-event terms listed are anemia, blood pressure increased, cellulitis, hemoglobin decreased, lymphadenopathy thoracic, and neutropenia, each recorded as 3.0%. These are separate listed terms and should not be summed to create an overall rate. The registry record does not explain the term-specific denominator or provide further detail about severity, timing, duration, or attribution.

Deaths are not reported in the registry record. The safety figures are distinct from the primary ORR endpoint and do not provide evidence about response. They also do not, on their own, provide a complete account of safety; interpretation is limited to the categories and information recorded in the entry.

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

The registry record makes the trial's central question clear: it intended to evaluate objective response rate for gemcitabine, cisplatin, and sunitinib in advanced or metastatic urothelial carcinoma. It also provides operational details about the endpoint definition, the intended analysis population, the recorded timeframe, and the study's single-group design. These registry entries describe what the study set out to examine, not what it found.

The primary ORR result is not reported in the registry record. Neither the response count nor the endpoint denominator nor the confidence interval is available. Consequently, the record cannot show how frequently response occurred in the intended analysis population or how precisely that frequency was estimated. It also cannot establish whether a response target was met, because a target and the relevant analysis are not reported.

The study has no separate comparator group in the registry description. Even a reported response rate would be a result for the treated group, rather than a randomized estimate of the difference between this combination and an alternative. Without a comparator, changes in outcome cannot be attributed to treatment by comparing groups within this design. This does not make the descriptive endpoint meaningless; it defines the narrower question the design can address.

The registry lists progression-free survival and OS as secondary outcomes, but their results and analysis details are not reported. The safety counts and serious adverse-event terms provide limited recorded safety information; they cannot fill the efficacy-results gap or establish a comprehensive safety profile. Likewise, completion status does not mean that endpoint results or statistical analyses are available in the registry record.

The most defensible interpretation is therefore bounded: this is a completed, single-group Phase II study with a stated response-rate objective, but the posted registry information is insufficient to quantify the observed response or its uncertainty. The absence of a posted result should not be interpreted as a zero response rate, as a negative finding, or as proof of benefit. It means that the quantitative result needed to make those judgments is not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates the distinction between a clearly stated clinical question and a reportable statistical result. The registry identifies the disease setting, treatment combination, primary outcome, response definitions, intended analysis population, and confidence-interval measure. Those details are useful for understanding what an ORR analysis would represent. But without a response estimate, denominator, or interval, readers cannot evaluate the endpoint's magnitude or precision.

The study also illustrates why design determines the scope of an inference. A single-group Phase II study can describe outcomes among treated participants, while a randomized comparison is needed to directly estimate a treatment contrast under the assigned study conditions. This distinction is especially important when a page reader encounters a response endpoint: a response proportion and a comparative treatment effect are different quantities, even when both relate to the same treatment.

Endpoint-population definition is another statistical issue made visible by the record. The stated population depends on eligibility, protocol-specified efficacy criteria, and receipt of at least 1 dose, while the enrollment figure alone does not specify the endpoint denominator. Reporting participant flow, response counts, analysis denominators, and uncertainty would allow readers to understand how the outcome was formed. Those details are not reported in the registry record.

Finally, the record separates efficacy questions from safety reporting. Serious adverse-event counts and listed terms are not substitutes for response results, and they require their own careful interpretation. Together, these features make the trial statistically instructive: the endpoint is defined, but the result and much of the analysis information are absent. That limits interpretation without justifying a favorable or unfavorable conclusion.

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 this trial from its registry record is that no primary outcome result is reported. The entry does not provide the response count, analysis denominator, ORR estimate, or confidence interval bounds. As a result, the principal study question cannot be answered quantitatively from the recorded information.

The registry's endpoint population is defined by eligibility, protocol-specified efficacy analysis requirements, and receipt of at least 1 dose, but the record does not identify how many participants met those criteria. It also does not provide participant flow, exclusions, missing response assessments, or the rule used for unevaluable outcomes. These omissions prevent assessment of whether the intended population and the analyzed population correspond.

The single-group, nonrandomized design has no separate comparator group. It can describe outcomes in the treated group, but cannot directly establish a randomized difference versus another treatment. The record does not provide enough information to assess how the study addressed potential sources of bias in response assessment or follow-up. Masking is recorded as none, while assessment procedures are not reported.

The registry does not list statistical analyses, the confidence-interval method, a multiplicity strategy, or the handling of secondary outcomes. It lists progression-free survival and OS, but does not report their definitions or results. The sample-size justification, interim-analysis plans, and detailed statistical plan are not reported in the registry record.

Safety information is also limited to the recorded at-risk and affected counts, selected serious adverse-event terms, and their listed percentages. The record does not report deaths or further detail on event duration, timing, attribution, or repeated events. These limitations should be understood as limits of the registry information, not as evidence that the unreported outcomes or analyses were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gemzar, Cisp, Sunitinib Urothelial Ca — NCT00821327.
• Registry record last updated 2016-10-25; status last verified 2016-09.
• Results first posted 2016-03-02.
• 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 record describes NCT00821327, a completed Phase II, single-group, nonrandomized, unmasked study sponsored by US Oncology Research. It enrolled 36 and evaluated gemcitabine, cisplatin, and sunitinib in advanced or metastatic urothelial carcinoma. The recorded study start was 2008-08, with primary completion on 2012-08.

The primary outcome was objective response rate, defined as complete or partial response, with a 2 years timeframe and a stated 95% confidence interval. The endpoint population was eligible patients meeting protocol-specified efficacy analysis requirements and receiving at least 1 dose. Progression-free survival and OS were listed as secondary outcomes.

The registry record does not report the primary endpoint estimate, response count, denominator, confidence interval bounds, secondary outcome results, or statistical analyses. It lists serious adverse-event and other adverse-event counts, along with selected serious-event terms. Thus, the study question and design are recorded, but the posted results are insufficient to assess the primary efficacy result or its precision.