Study Evaluating The Safety, Efficacy & Pharmacokinetics Of Temsirolimus(CCI-779) In Subjects With Advanced Renal Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating The Safety, Efficacy & Pharmacokinetics Of Temsirolimus(CCI-779) In Subjects With Advanced Renal Cell Carcinoma (NCT00494091), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Clinical Benefit.

2. Clinical Question

This is a question about the proportion of enrolled participants meeting a defined disease-response criterion over the stated follow-up timeframe. It is not a randomized estimate of the difference between temsirolimus and another treatment or a control condition. Without a concurrent randomized comparator, the endpoint describes outcomes in the study population rather than the causal effect of treatment relative to an alternative.

The record’s primary endpoint is labelled as a percentage of participants, and its stated precision measure is a 95% confidence interval. The registry record does not report the observed percentage or the confidence interval. It therefore does not provide the numerical result needed to describe how often clinical benefit occurred or how precisely that proportion was estimated.

3. Trial Design

The registry describes a phase 2, non-randomized, open-label study of temsirolimus (CCI-779) in subjects with advanced renal cell carcinoma. The model is listed as single-group, allocation as non-randomized, and masking as none. The study status is completed. The registry lists enrollment as 82, with a start date of 2007-02 and primary completion date of 2011-05.

The brief summary describes an evaluation of safety, efficacy, and pharmacokinetics in Asian patients. It says the trial was conducted in Japan, Korea, and China. These details establish the intended setting and scope, but do not provide demographic or clinical characteristics of the enrolled participants. Such characteristics are not reported in the registry record presented for this analysis.

The intervention listing contains temsirolimus (CCI-779), while the adverse-event record has groups titled Temsirolimus 20 mg/m^2 and Temsirolimus 25 mg. The arm descriptions are blank. The registry classifies the study as single-group, yet the safety record presents two dose-labelled groups. The record does not explain the relationship between these listings, so they should not be interpreted as randomized treatment arms or as a controlled comparison. The registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The primary endpoint is the percentage of participants with clinical benefit from baseline up to 4 years. Secondary outcomes listed are progression-free survival, percentage of participants with objective response, duration of response, time to treatment failure, and overall survival. The registry lists 12 outcome measures but does not list analysis results in the record. No analysis details, treatment schedule, or rationale for the enrollment target are reported in the registry record. The completed status indicates that the study is recorded as completed; it does not itself establish what the outcome estimates were.

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: Intent-to-treat (ITT) population included all participants who were enrolled in 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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Clinical Benefit, measured over Baseline Up to 4 years.

The primary endpoint is the percentage of participants with clinical benefit, with a timeframe from baseline up to 4 years. Clinical benefit is defined as confirmed complete response or partial response, or stable disease lasting at least 24 weeks. The registry describes complete response as disappearance of all target and nontarget lesions. Partial response requires at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions, using the baseline sum as the reference. Stable disease means neither enough shrinkage for partial response nor enough increase for progressive disease.

This composite endpoint groups different clinical courses under one binary classification: each participant either meets the stated clinical-benefit definition or does not. A proportion can be useful for describing how often a prespecified response-related outcome occurred in the study population. Requiring stable disease to last at least 24 weeks distinguishes sustained stability from a shorter period without sufficient change to meet the other response categories.

The endpoint is reported as a percentage, with a 95% confidence interval specified as its measure of dispersion. The population is the intent-to-treat population, defined in the record as all participants enrolled in the study. However, the registry record does not report the endpoint’s observed percentage or confidence interval. It therefore supports explanation of the outcome definition, but not a numerical account of the clinical-benefit result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For this endpoint, the statistical quantity of interest is a proportion: the share of participants in the intent-to-treat population who met the clinical-benefit definition. The registry labels the endpoint as a percentage of participants. A proportion is suited to an outcome recorded as whether each participant met a defined criterion. In general, the numerator is the count meeting the criterion and the denominator is the population used for the analysis. The registry record does not report the primary endpoint’s count, denominator used in the calculation, or percentage estimate.

What does the confidence interval describe?

The registry specifies a 95% confidence interval for the primary endpoint. In general, a confidence interval expresses statistical uncertainty around an estimate, reflecting the variation that could arise from sampling. A narrower interval usually indicates greater precision, while a wider interval indicates less precision. A confidence interval does not correct for bias in the design, measurement, or participant selection, and it does not make a non-randomized study comparable to a randomized one. Since the primary percentage and interval are not reported in the registry record, their width and the precision of the estimate cannot be assessed.

The stated confidence level is a feature of the inferential procedure, not a probability that the particular interval contains the true value after the interval has been calculated. In general, the confidence level describes the long-run coverage of an interval procedure under its assumptions. Those assumptions and the specific interval method used for this outcome are not reported in the registry record. No particular method, such as a normal approximation or an exact procedure, should therefore be attributed to the sponsor’s analysis.

How does the endpoint definition affect the estimate?

The endpoint combines confirmed complete response, confirmed partial response, and stable disease lasting at least 24 weeks. This makes it a composite binary outcome. In general, a composite outcome can capture more than one clinically relevant state, but its overall proportion depends on the definitions and on the contributions of each component. A single combined percentage would not reveal how many participants met each component unless component-specific counts were also reported. Those component results are not reported in the registry record.

Response classification depends on lesion measurements and the stated criteria. The registry describes complete response as disappearance of target and nontarget lesions, partial response as at least a 30 percent (%) decrease in the sum of the longest diameter of target lesions relative to baseline, and stable disease as neither enough shrinkage for partial response nor enough increase for progressive disease. The registry does not report the assessment schedule, independent review procedures, handling of unevaluable assessments, or rules for confirmation beyond the word “confirmed” in the response definition. Such details can affect outcome classification and are not available for interpretation.

What does the analysis population mean?

The endpoint population is identified as intent-to-treat, and the record defines it as all participants enrolled in the study. In general, an intent-to-treat approach aims to retain participants in the analysis population established at enrollment, rather than limiting analysis to those who complete treatment or have a particular post-enrollment experience. The registry record does not report how missing endpoint assessments, early discontinuations, or participants without evaluable response information were handled. It is therefore not possible to determine how the stated population definition was operationalized for the endpoint estimate.

Missing outcome information matters for a binary proportion because a participant with no evaluable status cannot simply be assumed to have met or not met the endpoint without an analysis rule. Different rules may yield different estimates. The registry record does not report imputation, censoring, or other missing-data methods for the primary outcome. No such procedure should be inferred from the intent-to-treat label alone.

Why is the design relevant to interpretation?

Random allocation, when used, can balance measured and unmeasured characteristics between groups on average. This study is listed as non-randomized, open-label, and single-group. General statistical interpretation must therefore distinguish a within-study outcome proportion from a treatment contrast. A proportion can describe what was observed in the enrolled group, but without a suitable concurrent comparison it does not isolate the effect attributable to treatment. The two dose-labelled groups in the safety record do not change that interpretation: the registry explicitly says the arms are not a like-for-like control comparison.

Open-label status means masking is listed as none. In general, knowledge of treatment assignment can affect care, assessment, or reporting, depending on the outcome and procedures. The registry does not report assessment blinding or independent review. No claim about the direction or size of any resulting bias can be made from the available record.

How should planning illustrations be read?

In general, a sample-size illustration based on an observed effect is a planning exercise, not a statement of the study’s observed power. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. The record says time-to-event illustrations give the total number of events, while other illustrations give participants per arm. These assumptions describe an illustration, not the design of this non-randomized single-group trial. The registry record does not report the trial’s own sample-size justification. Planning calculations cannot repair the absence of the primary endpoint estimate or supply evidence about the study’s observed result.

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("Temsirolimus 20 mg/m^2", "Temsirolimus 25 mg")
n      <- c(6, 76)
events <- c(3, 37)
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  Temsirolimus 20 mg/m^2  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6
ARM  Temsirolimus 25 mg  76  37  48.7  37.0  60.4  37.8  59.7  37.8  59.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary clinical-benefit endpoint and secondary outcomes that include progression-free survival, percentage of participants with objective response, duration of response, time to treatment failure, and overall survival. It also lists 12 outcome measures. When a study examines multiple outcomes, general statistical practice considers multiplicity because repeated testing can increase the chance of at least one apparently notable finding arising by chance. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan. It is not possible to determine whether or how multiplicity was addressed.

The record lists zero analyses, and numerical primary and secondary outcome results are not reported in the registry record. As a result, there is no set of reported effect estimates or p-values to interpret, and no basis for assessing consistency across outcomes. The outcome list alone should not be treated as evidence that any listed outcome met a statistical criterion.

The primary endpoint population is described as all enrolled participants, but missing-data procedures are not reported in the registry record. In general, absent or unevaluable outcomes can affect a binary proportion, especially when the handling rule determines whether a participant is counted as meeting the endpoint. The record does not state whether missing assessments were imputed, treated as non-response, excluded from an outcome-specific calculation, or handled another way. Those possibilities must not be assumed.

The registry also does not report a participant flow or endpoint-specific analysis denominator. The intent-to-treat definition identifies the intended population, but does not by itself show how many participants had an assessable endpoint or how missing observations were managed. Consequently, the precision and potential sensitivity of the endpoint estimate cannot be evaluated from the available record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: interstitial lung disease (33.3%), general physical health deterioration (16.7%), cellulitis (16.7%), pneumonia (16.7%), pericardial effusion (16.7%).

The safety record gives two dose-labelled groups. For Temsirolimus 20 mg/m^2, 6 participants were listed as at risk for serious adverse events and 4 as affected; for other adverse events, 6 were listed as at risk and 6 as affected. For Temsirolimus 25 mg, 76 participants were listed as at risk for serious adverse events and 28 as affected; for other adverse events, 76 were listed as at risk and 76 as affected. These are group-level registry figures, not estimates from a randomized comparison.

The serious adverse-event terms listed with percentages are interstitial lung disease at 33.3%, and general physical health deterioration, cellulitis, pneumonia, pericardial effusion, and cataract subcapsular at 16.7% each. The registry record does not explain the denominator or provide enough context to infer the frequency of these terms across a different population. The listed percentages should be interpreted as registry summaries, not as a comparison between dose groups.

Deaths are not reported in the registry record. The record does not provide further event-level detail, timing, duration, or treatment relationship for these adverse events. Because the study is non-randomized and the registry cautions that the groups are not a like-for-like comparison, differences in their figures cannot establish a causal dose-related safety contrast.

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

The registry establishes what the study intended to evaluate: safety, efficacy, and pharmacokinetics of temsirolimus in Asian patients with advanced renal cell carcinoma. It also defines clinical benefit as confirmed complete response or partial response, or stable disease lasting at least 24 weeks. The listed population for that endpoint is all participants enrolled, and the timeframe is baseline up to 4 years. These details allow a reader to understand the intended outcome and its classification.

The registry does not report the primary endpoint percentage or its 95% confidence interval. Therefore, it does not support a numerical statement about how many participants experienced clinical benefit, or how precisely that proportion was estimated. The absence of that estimate also prevents comparison of the primary endpoint with another study result on the same basis.

The study’s single-group, non-randomized design means that even a reported proportion would describe outcomes observed among enrolled participants rather than establish what would have happened under a different treatment. The safety group labels do not provide a randomized contrast, and the registry expressly warns that they are not a like-for-like control comparison. No causal difference between the dose-labelled groups can be inferred from those summaries.

The completion status and listed secondary outcomes do not fill the reporting gaps. The record does not report the results of the primary endpoint or the secondary outcomes. Nor does it report the missing-data procedures, analysis plan, or sample-size justification needed for a fuller appraisal. The appropriate conclusion is limited: the registry describes the study’s design, outcome definition, and some safety counts, but it does not report the primary clinical-benefit result needed to characterize the observed efficacy outcome.

14. Why This Trial Matters Statistically

This record illustrates why outcome definitions and outcome estimates need to be read separately. The primary endpoint is described in detail, including the response categories, lesion criteria, stable-disease duration, population, and timeframe. Yet the registry record does not report the endpoint’s percentage or confidence interval. A clear definition makes the intended measure interpretable, but cannot show what the study observed.

The design also matters. This is a non-randomized, open-label study classified as single-group. Its results, if reported, would describe outcomes in the enrolled study population. They would not by themselves estimate a treatment contrast against a concurrent randomized control group. The two safety group labels do not create such a contrast, and the registry warns that the groups are not a like-for-like comparison.

The record provides a further statistical lesson about precision and missing information. A 95% confidence interval is specified, but without the estimated proportion and interval there is no way to judge the precision of the primary result. Similarly, naming an intent-to-treat population does not reveal how missing endpoint assessments were handled. Such details affect interpretation of a proportion and should be available alongside the result.

Finally, a registry’s list of outcomes, design features, and safety counts has a different evidentiary role from a complete set of analysis results. The record lists several secondary outcomes and adverse-event summaries, but does not provide numerical primary endpoint findings. Separating documented methods from reported results prevents outcome definitions, completion status, or descriptive safety figures from being mistaken for evidence about the unreported primary result.

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 provides limited information for evaluating the primary endpoint. Although it specifies the outcome definition, timeframe, population, and confidence-interval type, it does not report the observed percentage or interval. The count meeting the endpoint and the endpoint-specific denominator are also not reported in the registry record. The primary efficacy result therefore cannot be assessed for magnitude or precision.

The study is non-randomized, open-label, and classified as single-group. There is no randomized control comparison in the record. The safety record’s dose-labelled groups should not be treated as controlled arms: the registry states that the arms are not a like-for-like control comparison, and the arm descriptions are blank. The record does not explain how the groups were formed or their relationship to the single-group model.

The registry does not report participant characteristics beyond the summary description of Asian patients with advanced renal cell carcinoma and the stated countries of conduct. It does not report the assessment schedule, independent review procedures, outcome-specific denominators, missing-data methods, or a statistical analysis plan. The sample-size justification is not reported in the registry record.

The registry lists secondary outcomes but does not report their results. It also does not report multiplicity procedures or the handling of missing assessments. The serious adverse-event summary contains counts and listed terms, but deaths are not reported, and event timing, duration, and treatment relationship are not specified. These limitations constrain both efficacy and safety interpretation; they do not establish that an unreported result was favorable or unfavorable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Evaluating The Safety, Efficacy & Pharmacokinetics Of Temsirolimus(CCI-779) In Subjects With Advanced Renal Cell Carcinoma — NCT00494091.
• Registry record last updated 2013-03-21; status last verified 2013-03.
• Results first posted 2012-07-09.
• 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

NCT00494091 is recorded as a completed phase 2, non-randomized, open-label study of temsirolimus (CCI-779) in subjects with advanced renal cell carcinoma. The registry lists enrollment as 82, a start date of 2007-02, and primary completion date of 2011-05. Its summary describes Asian patients and conduct in Japan, Korea, and China.

The primary endpoint was the percentage of participants with clinical benefit from baseline up to 4 years. Benefit was defined as confirmed complete response or partial response, or stable disease lasting at least 24 weeks. The intent-to-treat population was defined as all participants enrolled. The registry record does not report the primary endpoint percentage or its 95% confidence interval.

Secondary outcomes listed include progression-free survival, objective response, duration of response, time to treatment failure, and overall survival. Safety summaries are reported for two dose-labelled groups, but the registry cautions that they are not a like-for-like control comparison. The record does not report deaths, the statistical analysis plan, or missing-data procedures.