Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium (NCT00805129), a na phase 2 study. The primary outcome is Number of Participants Who Were Progression Free at 2 Months.

2. Clinical Question

The study asked whether everolimus could shrink or slow the growth of advanced urothelial cancer, while also examining safety. Its primary outcome focused on progression-free status at a defined timepoint rather than on a comparison between treatments. Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.

The question is therefore descriptive within the group receiving everolimus: how many participants met the record's definition of progression-free at 2 months? Without a control group, the study cannot directly estimate how that outcome compares with what would have happened under another treatment or under no study treatment. The record identifies response rate and the proportion of pretreatment primary tumor samples with mTOR pathway markers as secondary outcomes, but does not report their results in the information available for this analysis.

The registry lists an enrollment of 46. That is the recorded enrollment figure, not a reported count of participants who completed follow-up or were included in the primary endpoint analysis. Those analysis details, along with participant eligibility criteria and baseline characteristics, are not reported in the registry record. Consequently, the clinical question can be described, but its answer cannot be quantified from the reported primary endpoint information.

3. Trial Design

This was a Phase II, single-group study of everolimus in metastatic transitional cell carcinoma of the urothelium. Memorial Sloan Kettering Cancer Center is listed as the sponsor. The registry records an enrollment of 46 and a status of completed. The study start is recorded as 2008-12-05 and primary completion as 2021-12-15.

Everolimus was the only listed intervention. The arm description specifies 10 mg orally once daily continuously. The study is recorded as unmasked, with allocation listed as NA. Because it had a single group and no comparator, its design does not support a direct randomized, concurrent comparison of everolimus with another treatment. The registry explicitly indicates that arms are not a like-for-like control comparison; in this study, the design lists only the everolimus group.

The primary outcome was the number of participants who were progression free at 2 months. Progression was defined by RECIST v1.0: a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. The registry also identifies response rate and the proportion of pretreatment primary tumor samples with mTOR pathway markers as secondary outcomes. It records four outcome measures, but the details and results of all measures are not reported in the registry record.

A single-group Phase II design can describe outcomes observed among participants receiving the intervention. Its interpretation depends on the number assessed, endpoint definitions, follow-up, and how missing observations are handled. The registry information does not report the primary endpoint count, its analysis denominator, or an effect estimate. It also does not report a trial-specific sample-size justification or the statistical analysis plan. The recorded enrollment should therefore not be treated as the number analyzed for every outcome.

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:

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 Number of Participants Who Were Progression Free at 2 Months, measured over 2 months.

The primary endpoint counts participants who were progression free at 2 months. It is a binary-status outcome assessed at a specified time: each participant can be classified as progression free or not progression free according to the endpoint definition and available assessment. The registry describes progression using RECIST v1.0, including growth in target lesions, measurable growth in a non-target lesion, or new lesions.

Such a timepoint endpoint offers a straightforward clinical summary: the count, and ideally the proportion, meeting the progression-free definition at the stated assessment time. It can make the outcome interpretable without requiring that all participants have the same length of follow-up beyond that timepoint. General statistical interpretation still depends on knowing who was eligible for assessment, how many had an assessment, and how missing or unevaluable cases were classified. Those details are not reported in the registry record.

The registry names the endpoint as a number of participants, but the primary result itself is not reported in the record information used for this analysis. No endpoint count, denominator for the analysis, proportion, confidence interval, or comparison estimate is available. The endpoint definition explains what was intended to be measured; it does not by itself establish how many participants met the definition.

Progression-free status is distinct from response rate. The registry lists response rate separately as a secondary outcome, but does not provide its result or detailed measurement approach. No inference about that secondary outcome should be substituted for the missing primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is expressed as a count of participants meeting a binary condition: progression-free status at 2 months. General statistical interpretation of a count begins with its denominator. A count alone does not indicate how common an outcome was unless the number assessed is also known. The registry lists an enrollment of 46, but does not report the primary endpoint count or the analysis denominator. It is not valid to assume that every enrolled participant contributed an evaluable endpoint.

What does a timepoint count capture?

A timepoint outcome asks whether each participant meets the specified condition at a particular assessment. Here, the condition is progression-free status at 2 months according to RECIST v1.0. This differs from a time-to-event analysis, which uses the timing of events and can account for differing follow-up through methods designed for censored observations. The primary outcome is registered as a participant count, not as a time-to-event estimate. The record does not report a time-to-event analysis for this endpoint.

In general, timepoint analyses require clear rules for participants who lack an assessment at the chosen time. Possible approaches can produce different estimates, so the missing-data rule matters. The registry record does not report how missing, unevaluable, or delayed assessments were handled. It also does not describe the assessment schedule beyond the stated 2-month timeframe. No particular handling rule should be presumed.

How does RECIST define progression?

RECIST provides criteria for evaluating changes in tumor lesions. In this registry record, progression includes a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. These criteria make the endpoint definition more explicit than a general description such as worsening disease. The record does not provide imaging details, independent review procedures, or additional adjudication rules.

General measurement principles still apply: consistency in lesion assessment and endpoint classification is important because errors in classification can affect a binary outcome. The study was unmasked, so masking is not part of the registered design. The record does not report whether any independent or blinded endpoint review was used. The absence of that detail does not establish that no such process occurred; it means it is not reported in the registry record.

What would an uncertainty interval add?

Generally, a confidence interval around a proportion would communicate sampling uncertainty in the estimated frequency of the outcome. It would not account automatically for all sources of bias, nor would it make a single-group study equivalent to a controlled comparison. To interpret such an interval, readers need the observed count, denominator, and method used to construct it. Those endpoint results and methods are not reported in the registry information. No confidence interval or p-value for the primary outcome can be described.

For a binary count, statistical models often begin with a binomial framework, which treats each participant's outcome as one of two categories and estimates the event frequency. The suitability of a model depends on the analysis and data structure. Over-dispersion is a general concern when observed variability exceeds what a model assumes; it is not something that can be diagnosed from a missing endpoint count. The record does not report an over-dispersion assessment or a model for the primary outcome.

What do the planning assumptions mean?

The registry information describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is stated as a fraction of the observed effect. For time-to-event illustrations, the specified quantity is a total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These are planning assumptions, not evidence that the trial used a two-arm design. The actual study is recorded as single-group.

Such sample-size calculations are planning illustrations, not observed power. They do not show the power achieved by the completed study. They also cannot be interpreted without the effect estimate used to anchor the illustration. The primary endpoint count and effect estimate are not reported in the available record information, and no values from a planning illustration are stated. A trial-specific sample-size justification is not reported in the registry record.

Finally, the registry records no analyses. That does not reveal which calculations may have been conducted outside the registry; it means no analysis entries are listed in the record information used. The sponsor's own analysis would take precedence over any simple unadjusted recalculation if a discrepancy were identified, but no recalculated primary outcome is available from the information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and identifies the primary measure as the number of participants progression free at 2 months. It also names response rate and the proportion of pretreatment primary tumor samples with mTOR pathway markers as secondary outcomes. The complete details for all four measures, including results, are not reported in the registry information available for this analysis.

Multiplicity is a general issue when a study examines multiple outcomes or multiple statistical tests. If many hypotheses are tested, the chance of at least one apparently unusual result can rise unless the analysis plan accounts for the testing structure. Appropriate interpretation depends on knowing which outcomes were prespecified, which analyses were performed, and whether any adjustment or hierarchy was used. The registry record does not report a multiplicity strategy, a statistical analysis plan, or analysis entries. It is therefore not possible to determine whether or how multiplicity was addressed.

Missing-data methods also affect interpretation. For the primary timepoint endpoint, a reader would need to know how participants without an evaluable 2-month assessment were treated and whether analyses used all enrolled participants or a defined subset. The registry record does not report those rules or the primary analysis denominator. No imputation method, sensitivity analysis, or missingness summary is reported in the available information.

Analysis populations are likewise not described. The record does not specify an intention-to-treat, per-protocol, safety, or other population for the primary efficacy analysis. The enrollment figure should not be interpreted as a confirmed analysis population. Without the analysis set, missing-data approach, and outcome results, the robustness of any primary estimate cannot be evaluated from the registry record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death not assoc w ctcae term-disease prog nos (8.7%), dyspnea (shortness of breath) (6.5%), confusion (4.3%), dehydration (4.3%), fatigue (asthenia, lethargy, malaise) (4.3%).

The registry's adverse-event information lists an everolimus group with 46 participants at risk for serious adverse events and 23 affected. For other adverse events, it lists 46 at risk and 39 affected. It also lists 43 deaths. These are separate registry counts; the record does not explain whether participants appear in more than one category, so the counts should not be combined.

The listed serious adverse-event terms include death not associated with a CTCAE term—disease progression NOS at 8.7%, dyspnea at 6.5%, and confusion, dehydration, fatigue, and fever at 4.3% each. The record identifies fever as occurring in the absence of neutropenia. These percentages are reported as given; the information available does not specify further details about their calculation or event timing.

Adverse-event counts describe events recorded during the study, not proof of causation. The registry information does not report an attribution assessment, timing by treatment exposure, event duration, or whether the deaths were related to treatment. The listed count of deaths should therefore not be read as a count of deaths caused by everolimus. These figures are also not a comparison with an untreated or control group, because the study is single group.

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

The study establishes a registered clinical question and a defined way to assess progression-free status at 2 months. Its design and intervention are described: participants received everolimus continuously at 10 mg orally once daily in a single-group, unmasked Phase II study. The registry also records adverse-event counts and names secondary outcomes.

What the record does not establish in the information available for this analysis is the primary outcome result. There is no reported count of participants progression free at 2 months, no analysis denominator, and no estimate of precision. The endpoint definition cannot substitute for an observed result. Nor can the enrollment of 46 be assumed to be the number included in the endpoint analysis.

Even if a single-group primary result were available, it would describe outcomes in the treated group rather than establish a difference attributable to everolimus. Without a comparator, the study cannot directly distinguish the intervention's effect from other factors that may influence outcomes. This is a general design limitation and does not determine the direction or size of any actual effect.

The safety counts should be read in the same descriptive way. They record affected participants and listed events, but the registry information does not establish causation or offer a control-group rate for comparison. The listed deaths cannot be attributed to treatment on the basis of the count alone.

Accordingly, the record supports a cautious account of the trial's purpose, design, endpoint definition, and recorded safety information. It does not support a numerical conclusion about progression-free status, a treatment-effect estimate, or a claim that everolimus did or did not alter outcomes. Results for the named secondary outcomes and details of missing-data handling and analysis populations are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly named endpoint and a reported endpoint result. The registry defines progression-free status at 2 months using RECIST v1.0, but the count needed to answer the primary question is not reported in the record information. A definition makes an outcome reproducible in principle; it does not disclose the observed data.

The single-group design is equally important to interpretation. A study can describe outcomes among participants receiving an intervention, but without a comparator it cannot directly estimate a concurrent treatment contrast. This distinction helps prevent descriptive outcomes from being mistaken for evidence of comparative effectiveness. The registry lists allocation as NA and masking as none, consistent with the absence of a randomized control comparison.

The safety entries also illustrate why counts, denominators, and causal attribution need to be kept separate. The record lists numbers at risk and affected for serious and other adverse events, as well as deaths and selected event terms. These data are useful for describing what the registry records, but they do not establish treatment causation or provide a control-group comparison.

Finally, the record gives limited information about analysis methods. The lack of registered analyses, missing-data rules, and analysis-population definitions constrains any assessment of precision or robustness. Statistical interpretation depends not only on an outcome label but also on the observed result, denominator, uncertainty, and analysis choices. When those elements are not reported, a careful reading should preserve the distinction between what the study set out to measure and what can be concluded from its recorded results.

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 central limitation for interpreting this trial from the registry information available is the absence of a reported primary endpoint result. The record identifies progression-free status at 2 months as the primary outcome and defines progression using RECIST v1.0, but provides no corresponding count, analysis denominator, proportion, or confidence interval. The registered enrollment of 46 does not show how many participants were assessed or included in an analysis.

The single-group design limits causal and comparative interpretation. There is no control arm against which to estimate a treatment difference, and the study is recorded as unmasked. The registry information does not report whether endpoint review was independently conducted or whether other procedures were used to address possible assessment bias.

Participant-level context is limited. Detailed eligibility criteria, baseline characteristics, follow-up completeness, and endpoint assessment details are not reported in the information available. The record does not state how missing or unevaluable assessments were handled, which analysis population was used, or whether sensitivity analyses were performed. These omissions make it difficult to judge the representativeness and precision of any potential outcome estimate.

Four outcome measures are recorded, with response rate and pretreatment primary-tumor mTOR pathway markers identified among the secondary outcomes. Their results and the full details of all measures are not available. The statistical analysis plan, multiplicity approach, interim analyses, and trial-specific sample-size justification are not reported in the registry record. Safety counts are descriptive, and the available information does not establish causality or explain overlap among event categories.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus (RAD001) in Metastatic Transitional Cell Carcinoma of the Urothelium — NCT00805129.
• Registry record last updated 2022-11-25; status last verified 2021-12.
• Results first posted 2022-11-25.
• 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.

18. Record Summary

The registry records NCT00805129 as a completed Phase II, single-group, unmasked study of everolimus in metastatic transitional cell carcinoma of the urothelium. Memorial Sloan Kettering Cancer Center is listed as sponsor. Enrollment is recorded as 46; the study start is 2008-12-05 and primary completion is 2021-12-15.

Everolimus was administered at 10 mg orally once daily continuously. The primary outcome was the number of participants progression free at 2 months, assessed using RECIST v1.0. The registry names response rate and the proportion of pretreatment primary tumor samples with mTOR pathway markers as secondary outcomes. It does not report the primary endpoint result in the information available for this analysis.

The adverse-event record lists 23 affected participants among 46 at risk for serious events, 39 among 46 at risk for other events, and 43 deaths. These counts do not establish treatment causation. Statistical analysis details, analysis populations, missing-data methods, and the trial-specific sample-size justification are not reported in the registry record.