This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma (NCT01524991), a na phase 2 study. The primary outcome is Median Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01524991 |
| Phase | Phase 2 |
| Condition | Urothelial Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoosier Cancer Research Network |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced or metastatic urothelial carcinoma were the population named in the primary endpoint description. The condition is listed as urothelial carcinoma, and enrollment was 36. Further eligibility criteria and characteristics of the enrolled participants are not reported in the registry record.
Intervention
The treatment combined gemcitabine, cisplatin, and ipilimumab. The treatment description specifies gemcitabine 1000 mg/m2 on Days 1 & 8, cisplatin 70 mg/m2 on Day 1, and ipilimumab 10 mg/kg on Day 1 starting in cycle 3. The record does not provide further details about treatment duration or dose modifications.
Comparator
This was a single-group trial, with no randomized comparator recorded. The treatment group therefore has no concurrent control group in this trial against which to estimate a comparative treatment effect.
Primary question
The stated primary question was to determine median overall survival among patients treated with the combination. Overall survival was defined from registration until the date of final analysis, with the study description projecting that analysis at 48 months from study start. The median estimate and its 95% confidence interval are not reported in the registry record.
The trial’s question is about survival following a treatment regimen in a specified patient group, rather than a randomized comparison between two regimens. That distinction shapes what can be concluded: a single-group estimate can describe outcomes among participants, but it cannot, by itself, establish how those outcomes compare with what would have occurred under another treatment or usual care. The registry describes the combination as first-line treatment and lists progression-free survival, best overall response rate, and adverse events as secondary outcomes. Results for those outcomes are not reported in the registry record.
The registry’s background states that gemcitabine plus cisplatin is standard treatment for advanced urothelial cancer and that ipilimumab had shown activity as neoadjuvant therapy in localized bladder cancer. Those statements provide the stated rationale for investigating the combination; they are not results of this trial. The clinical question that can be addressed from the posted record is therefore limited: it identifies the population, regimen, and intended survival endpoint, but it does not provide the endpoint estimate needed to describe the observed survival result.
3. Trial Design
The registry identifies this study as phase II and completed, with an enrollment of 36. It records a single-group model, no masking, and allocation as NA. There is no randomized control group described. The sponsor is Hoosier Cancer Research Network, and the official title identifies the study as GU10-148. Dates and further operational details are not necessary to interpret the basic design, and additional protocol details are not reported in the registry record.
All participants were assigned to the treatment group described in the record: gemcitabine, cisplatin, and ipilimumab. Gemcitabine is specified at 1000 mg/m2 on Days 1 & 8, cisplatin at 70 mg/m2 on Day 1, and ipilimumab at 10 mg/kg on Day 1 starting in cycle 3. The record does not report whether every participant received every planned dose, how long treatment continued, or what rules governed interruptions, reductions, or discontinuation.
A single-group phase II design can describe outcomes among people receiving the regimen and can support investigation of whether a treatment merits further study. Without a concurrent randomized comparator, however, an outcome such as survival cannot be attributed to the regimen by comparing trial participants with a control group from the same trial. Differences in participant characteristics, clinical setting, follow-up, and other factors can complicate comparisons with external experience. No such external comparison is reported as a trial analysis.
The primary endpoint was median overall survival, with the timeframe described as 48 months. The endpoint description says survival was calculated from registration until the date of final analysis and notes that the final analysis was projected to occur 48 months from study start. The registry status is completed, but the primary estimate and its confidence interval are not reported in the registry record. The record lists three secondary outcome areas: progression-free survival, best overall response rate, and number of adverse events experienced by patients. Their outcome results are also not reported in the registry record.
Information about the planned sample-size justification, enrollment targets beyond the recorded enrollment, stopping rules, interim analyses, eligibility details, and analysis populations is not reported in the registry record. The record lists zero analyses. This limits assessment of how the trial was intended to handle its endpoint data and how closely the available outcome reporting reflects the original statistical plan.
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
| Stage | Treatment |
|---|---|
| STARTED | 36 |
| COMPLETED | 2 |
| NOT COMPLETED | 34 |
Reasons for not completing this period:
| Reason | Treatment |
|---|---|
| Adverse Event | 12 |
| Death | 1 |
| Disease ProgressionDu | 17 |
| Other complicating disease | 1 |
| Withdrawal by Subject | 2 |
| Symptomatic Deterioration | 1 |
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.
| Characteristic | Unit | Treatment |
|---|---|---|
| Participants analysed | 36 | |
| Age, Continuous | years | 36 (33 to 80) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 29 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 32 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 35 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 36 |
| Karnovsky Performance Status: KPS 100 | Participants | 9 |
| Karnovsky Performance Status: KPS 90 | Participants | 16 |
| Karnovsky Performance Status: KPS 80 | Participants | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Median Overall Survival, measured over 48 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is median overall survival, measured in months. The registry describes the time origin as the date of registration and the endpoint event as death, with follow-up through the date of final analysis. The specified timeframe is 48 months, and the endpoint description states that final analysis was projected to occur 48 months from the start of the study. The median overall survival result and its 95% confidence interval are not reported in the registry record.
In general, overall survival is a time-to-event endpoint: it measures the time from a defined starting point until death. It is commonly used in clinical trials because the event has a direct interpretation and does not depend on a judgment about whether a tumor has progressed or responded. A median is the time by which half of the observed population has experienced the event, under the assumptions of the analysis. When some participants have not had the event by the end of their observed follow-up, their information is typically treated as censored rather than as if the event occurred at the end of follow-up.
In general, a confidence interval expresses uncertainty around an estimate. Its width conveys how precisely the median has been estimated; it does not make the estimate a guarantee for an individual or show what would have happened under a different treatment. The registry record does not report the method used to estimate the median, how censoring was handled, or the confidence-interval procedure. Without the estimate and interval, the posted record does not permit a numerical description of the primary endpoint or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed phase II, single-group trial enrolling 36 participants and names median overall survival as its primary endpoint. It does not report a median overall survival estimate or a 95% confidence interval. Consequently, the posted information does not establish the observed survival time or the precision of an estimate. The completion status does not substitute for a reported endpoint result.
The record also lists progression-free survival, best overall response rate, and adverse events as secondary outcomes, but does not report their outcome results. It lists four outcome measures and zero analyses. The available information therefore supports a description of the intended endpoints, not an assessment of their observed values or statistical uncertainty. It is not possible from this record to determine whether any endpoint met a prespecified threshold, how outcomes varied among participants, or what analyses were performed beyond the information explicitly recorded.
There is no concurrent randomized comparator. Thus, even if an outcome estimate were available, this design would describe outcomes in the treated group rather than provide a randomized estimate of the difference between this regimen and another option. General statistical explanation: a single-arm outcome may be affected by patient selection, disease characteristics, care practices, follow-up, and chance. External comparisons can be informative in some settings, but they are not equivalent to randomized comparisons and require careful alignment of populations and methods. The registry record does not report an external comparison.
The primary endpoint description indicates a 48-month timeframe and defines the time origin as registration. It says the final analysis was projected for 48 months from the start of the study. That description does not supply the number of participants with observed events, the amount of follow-up, or the handling of censored observations. Those details matter for understanding a time-to-event estimate, and they are not reported in the registry record.
The safety data list 36 participants at risk for both serious and other adverse events. Serious adverse events affected 18 participants, and other adverse events affected 36 participants. The record also lists 28 deaths. These counts are descriptive; the record does not give a comparison group or establish which events were caused by the treatment. The listed serious adverse-event terms and percentages provide additional descriptive information, but they do not resolve causation or quantify comparative risk.
In general, estimates from a small single-group study are subject to uncertainty, and an estimate of a treatment outcome is not, on its own, evidence of a causal effect. Because the primary endpoint result, its interval, and sponsor-reported analyses are absent, no numerical conclusion about the trial’s survival outcome can be drawn from the registry record. A careful reading distinguishes the documented design and safety counts from results that are not reported.
9. Statistical Methods Explained
The registry identifies a time-to-event primary endpoint: median overall survival. It specifies a 95% confidence interval as the measure of dispersion and gives a timeframe of 48 months. However, it does not report the median, interval limits, or sponsor-reported analyses. The registry record therefore does not provide the output needed to evaluate the size or precision of the primary endpoint estimate.
What does a median survival estimate mean?
General statistical explanation: a time-to-event analysis uses both the time until an event and information about participants whose event has not been observed by the time their follow-up ends. Those participants are generally censored at their last known follow-up rather than treated as though the event occurred then. The median is the estimated point in time at which the survival curve reaches one half. It is a population-level summary, not a prediction that every participant will experience the event at that time.
The endpoint description defines registration as the time origin and death as the event of interest. It describes a projected final analysis at 48 months from study start. It does not report individual follow-up, the number of deaths used in the primary analysis, the censoring rules, or the method for estimating the median and its confidence interval. Those details are important because time-to-event estimates depend on the recorded event times and follow-up. They should not be inferred from the endpoint label alone.
How should a confidence interval be read?
General statistical explanation: a confidence interval describes the uncertainty associated with an estimate under the assumptions of the statistical procedure used. A narrower interval indicates greater precision than a wider interval, while neither interval width nor its location establishes a causal treatment effect. A confidence interval for a single-group median describes uncertainty about that group’s estimate; it does not compare the group with an unobserved or external control. Since the interval is not reported in the registry record, the precision of the median cannot be assessed.
What can a single-group design estimate?
General statistical explanation: a single-group study can characterize outcomes in the enrolled group. It does not create a randomized contrast that balances measured and unmeasured prognostic factors between treatment groups. A comparison with historical or external outcomes may be vulnerable to differences in eligibility, disease severity, follow-up, and care. The registry records no randomized comparator and does not report an external-comparison analysis. Accordingly, the treatment group’s outcomes, if reported, would need to be interpreted as observed outcomes in that group, not as a randomized estimate of benefit relative to another regimen.
What is the role of the listed secondary outcomes?
The registry lists progression-free survival, best overall response rate, and number of adverse events experienced by patients as secondary outcomes. In general, progression-free survival is a time-to-event measure involving disease progression or death, while response rate summarizes the proportion meeting response criteria. Their interpretation depends on endpoint definitions, assessment schedules, and analysis rules. The definitions, assessment details, and results for these outcomes are not reported in the registry record. The adverse-event outcome is listed, but its methods and full results are not reported either.
What does over-dispersion mean in general?
General statistical explanation: over-dispersion occurs when variability in count data is greater than a model assumes. If ignored, standard errors can be too small and uncertainty can be understated. This concept may matter for some count outcomes, but the registry record does not report a count-data model or an analysis requiring an over-dispersion assessment. It would not be appropriate to claim that such a method was used in this trial.
What is reported about the analysis plan?
The registry lists zero analyses. It does not report the statistical plan, the method used for the primary endpoint, any interim analyses, multiplicity procedures, or the approach to missing data. It also does not report whether analyses were conducted in an intention-to-treat, per-protocol, or other population. These omissions prevent a detailed audit of the analysis choices and their alignment with the planned design.
Planning sample-size illustrations, when used, are not observed trial outcomes and are not a substitute for the trial’s own design justification. The registry record does not report a sample-size justification. In general, a sample-size calculation depends on assumptions about the effect to detect, variability or event rates, significance level, power, and allocation. Without the original assumptions and protocol, the justification cannot be reconstructed from the recorded enrollment alone. Likewise, an illustrative calculation should not be interpreted as observed power or as evidence that an endpoint effect occurred.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists median overall survival as the primary outcome and names progression-free survival, best overall response rate, and adverse events as secondary outcomes. It records four outcome measures and zero analyses. The analysis plan, the relationship among the outcomes, and any prespecified testing hierarchy are not reported in the registry record. It is therefore not possible to determine whether the study planned a formal adjustment for multiple statistical tests or how any such procedure would have been applied.
General statistical explanation: when multiple outcomes or repeated tests are considered, the chance of at least one apparently unusual result can increase if each test is interpreted separately. Multiplicity procedures can help manage that issue, but the appropriate approach depends on the study questions and prespecified plan. No multiplicity method should be attributed to this trial without documentation.
Missing-data rules and the amount of missing endpoint information are not reported in the registry record. For overall survival, participants may have follow-up that ends before death is observed; general time-to-event methods typically account for this through censoring, but the specific approach used is not reported. The record also does not describe missing assessments for progression-free survival or response outcomes, or how such observations would have been handled.
The analysis populations are not described. The registry record does not say whether the intended analysis included all enrolled participants, only those who received treatment, or another defined group. Although enrollment is recorded as 36, that number alone does not identify the denominator used for any endpoint analysis. Without population definitions, endpoint results, and a statistical plan, readers cannot assess exclusions or determine whether the analysis followed the intended approach.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment | 18 | 36 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment | 28 of 36 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment | 36 of 36 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment |
|---|---|---|
| THROMBOEMBOLIC EVENT | Vascular disorders | 5 of 36 |
| FEVER | General disorders | 4 of 36 |
| ACUTE KIDNEY INJURY | Renal and urinary disorders | 3 of 36 |
| URINARY TRACT INFECTION | Infections and infestations | 3 of 36 |
| ATRIAL FIBRILLATION | Cardiac disorders | 2 of 36 |
| AUTOIMMUNE DISORDER | Immune system disorders | 2 of 36 |
| DIARRHEA | Gastrointestinal disorders | 2 of 36 |
| ADRENAL INSUFFICIENCY | Endocrine disorders | 1 of 36 |
| ANEMIA | Blood and lymphatic system disorders | 1 of 36 |
| COLITIS | Gastrointestinal disorders | 1 of 36 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment |
|---|---|---|
| FATIGUE | General disorders | 33 of 36 |
| NAUSEA | Gastrointestinal disorders | 27 of 36 |
| ANEMIA | Blood and lymphatic system disorders | 24 of 36 |
| CONSTIPATION | Gastrointestinal disorders | 24 of 36 |
| DIARRHEA | Gastrointestinal disorders | 23 of 36 |
| NEUTROPHIL COUNT DECREASED | Investigations | 21 of 36 |
| ANOREXIA | Metabolism and nutrition disorders | 19 of 36 |
| COUGH | Respiratory, thoracic and mediastinal disorders | 18 of 36 |
| HYPONATREMIA | Metabolism and nutrition disorders | 17 of 36 |
| PLATELET COUNT DECREASED | Investigations | 17 of 36 |
Serious events with the highest arm-level rate: thromboembolic event (13.9%), fever (11.1%), acute kidney injury (8.3%), urinary tract infection (8.3%), atrial fibrillation (5.6%).
The registry reports serious adverse events for a treatment group with 36 participants at risk; 18 were affected. It reports other adverse events for 36 participants at risk, with 36 affected. The record lists 28 deaths. These are descriptive counts in the posted record, not comparisons with another treatment group. The record does not report whether deaths were attributed to the disease, treatment, or another cause, and the listed count should not be interpreted as a treatment-related death count.
The most frequently listed serious adverse-event terms are thromboembolic event at 13.9%, fever at 11.1%, acute kidney injury at 8.3%, urinary tract infection at 8.3%, atrial fibrillation at 5.6%, and autoimmune disorder at 5.6%. These percentages are registry-record values. They describe the listed events in this group; they do not establish causation or comparative safety. The record does not provide event-specific denominators, timing, duration, severity beyond the serious classification, or recurrence information for these terms.
General statistical explanation: an adverse-event count is not the same as an event rate over time, and a participant affected by more than one event may contribute to more than one event category. Comparisons of safety usually require consistent definitions, observation periods, and denominators across groups. Because this is a single-group trial with no randomized comparator recorded, the listed figures do not provide a comparative estimate of safety.
12. What the Result Does, and Does Not, Mean
The trial is described as a completed phase II, single-group study of gemcitabine, cisplatin, and ipilimumab in advanced or metastatic urothelial carcinoma. Enrollment was 36, and median overall survival was the primary endpoint. Those details characterize the design and question, but they do not supply the endpoint result. The median and its 95% confidence interval are not reported in the registry record.
The registry’s background explains why the combination was investigated, including the stated role of gemcitabine plus cisplatin in advanced urothelial cancer and the prior activity of ipilimumab described in localized disease. These background statements are not evidence of the outcome in this trial. The secondary outcomes are named, but their results are not reported in the registry record. Therefore, the posted information does not show the observed progression-free survival, response rate, or complete adverse-event experience.
A single-group study can describe outcomes among the people enrolled, but it does not produce a randomized comparison with another treatment. Even a reported survival estimate would not, by itself, show what the same participants would have experienced under a different regimen. General statistical explanation: causal comparisons are strengthened by design features that make treatment groups comparable, such as random allocation. No randomized comparator is recorded for this study.
The safety counts document that serious and other adverse events were recorded in the treatment group, with the listed terms and percentages. They do not show that the regimen caused each event, nor do they establish how the counts compare with another regimen. The number of deaths is also a descriptive count; attribution and comparative mortality are not reported.
The distinction is between what the registry documents and what remains unknown. It documents the intended primary endpoint, treatment details, design, enrollment, and selected safety information. It does not report the survival estimate, confidence interval, secondary outcome results, analysis plan, or analysis populations. A numerical conclusion about the primary endpoint or a comparative conclusion about treatment effects would go beyond the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and results must be read together. The record identifies a clinically meaningful time-to-event endpoint, median overall survival, and reports a 95% confidence interval as its intended measure of uncertainty. Yet it does not report the estimate or interval. Naming an endpoint does not reveal its observed value, and a completed status does not establish that a result is available in the registry record.
The single-group design is equally important. The study can be understood as investigating outcomes among participants receiving the combination, but it does not include a randomized comparison. This limits the kind of treatment-effect claim that the design could support, even if the outcome estimates were present. A within-group survival summary is not the same as an estimate of the difference between treatment options.
The record also illustrates how endpoint multiplicity and analysis transparency affect interpretation. Several secondary outcome areas are listed, but no outcome analyses are recorded. The statistical plan, handling of missing data, analysis populations, interim analyses, and multiplicity procedures are not reported in the registry record. Without these details, readers cannot verify how endpoint definitions and analysis choices were applied.
The safety information is valuable as a description of reported events, but it is not a causal or comparative assessment. Counts and percentages need context about denominators, follow-up, event definitions, and attribution. The record gives some denominators and selected serious-event terms, but does not report enough detail to support a full comparative safety interpretation.
The central statistical lesson is one of calibrated interpretation: separate trial design, observed estimates, uncertainty, and causal comparison. Here, the design and selected safety counts are documented, while the primary and secondary outcome results are not reported in the registry record. Maintaining that distinction avoids treating a study rationale or endpoint label as if it were an outcome finding.
14. 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 most consequential limitation of the registry record is that it does not report the primary endpoint result. Median overall survival and its 95% confidence interval are both absent, so the observed survival estimate and its precision cannot be described. The record’s completed status does not fill that reporting gap.
The study is single-group, with allocation recorded as NA and no randomized comparator. Thus, the design does not provide a concurrent randomized comparison of the combination with another treatment. Any outcome description would pertain to the enrolled treatment group and could not, by itself, isolate a causal treatment effect.
Enrollment is recorded as 36, but the number included in each endpoint analysis and the analysis populations are not reported in the registry record. The record also does not report participant characteristics, eligibility details, follow-up completeness, censoring rules, missing-data handling, or the method used to estimate the primary endpoint. These omissions limit assessment of representativeness, precision, and potential sources of bias.
The record names secondary outcomes but does not report their results or the methods used to analyze them. It also lists zero analyses and does not report the statistical plan, interim analyses, multiplicity procedures, or sample-size justification. The safety information is limited to listed counts and selected serious adverse-event terms; event timing, attribution, and comparison with another group are not reported.
These limitations concern what can be concluded from the registry record; they do not establish that unreported analyses or protocol details were absent from other study documents. In general, registry reporting and full clinical study reporting may differ in detail. Any additional conclusions require information not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: First-Line Gemcitabine, Cisplatin + Ipilimumab for Metastatic Urothelial Carcinoma — NCT01524991.
- Registry record last updated 2022-07-11; status last verified 2022-07.
- Results first posted 2019-11-29.
- 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.
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18. Record Summary
The registry describes a completed phase II, single-group trial of gemcitabine, cisplatin, and ipilimumab as first-line treatment for metastatic urothelial carcinoma. Enrollment was 36. The regimen lists gemcitabine 1000 mg/m2 on Days 1 & 8, cisplatin 70 mg/m2 on Day 1, and ipilimumab 10 mg/kg on Day 1 starting in cycle 3.
The primary endpoint was median overall survival, with a 95% confidence interval and a 48-month timeframe. The median result and interval are not reported in the registry record. Secondary outcomes listed are progression-free survival, best overall response rate, and adverse events; their results are not reported. The record lists zero analyses.
For safety, 18 of 36 participants were affected by serious adverse events, 36 of 36 by other adverse events, and 28 deaths are listed. Selected serious-event terms and percentages are reported, but no randomized comparator is recorded. The safety figures are descriptive and do not establish causation or comparative risk.