Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients (NCT00919035), a na phase 2 study. The primary outcome is Overall Clinical Benefit From Torisel® in Chemotherapy-naïve Castration Resistant Prostate Cancer (CRPC)..

2. Clinical Question

The trial asks whether single-agent temsirolimus is associated with clinical benefit in chemotherapy-naïve patients with castration-resistant prostate cancer. The primary outcome defines benefit as a complete response, partial response, or stable disease. These categories are based on lesion measurements, imaging findings, and, for complete response, the absence of disease-related symptoms as specified in the registry record.

This is a question about outcomes observed within a treated group, not a randomized comparison of temsirolimus against another treatment or usual care. Without a concurrent comparator, changes over time cannot be separated confidently from other influences using the trial design alone. The record also lists time to disease progression and change in prostate-specific antigen doubling time before and after treatment as secondary outcomes, but their results are not reported in the registry record.

3. Trial Design

The study is registered as a phase II trial with a single-group model and no masking. Its brief summary describes a single-institution, open-label study of chemotherapy-naïve patients with androgen-independent prostate cancer. The registry lists 21 enrolled participants. The intervention is single-agent temsirolimus (Torisel®), described in the study summary as 25 mg weekly.

Treatment was intended to continue until disease progression, participant withdrawal, unacceptable toxicity, or investigator discretion. The primary endpoint’s timeframe describes assessment of disease progression every 2 cycles, for up to 40weeks, from the first dose to the date the participant was taken off study. The registry does not give further details about the timing or conduct of visits beyond this endpoint description.

Because this is a single-group, open-label study, participants and investigators were not masked to treatment, and there was no randomized control group. Allocation is listed as not applicable. The design can describe outcomes and safety observations among people treated in the study, but it does not provide a like-for-like comparison with an untreated group or a different treatment arm. The registry’s listed secondary outcomes are time to disease progression and change in prostate-specific antigen doubling time before and after treatment.

The study is marked completed. Its start is listed as 2009-06, and primary completion as 2013-02. The sponsor is Oncology Specialists, S.C. The record identifies the study as phase II, but a sample-size justification, detailed protocol, planned interim analyses, and detailed statistical analysis plan are not reported in the registry record. The primary outcome is defined, but its observed result and an analysis of that result are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall 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 Overall Clinical Benefit From Torisel® in Chemotherapy-naïve Castration Resistant Prostate Cancer (CRPC)., measured over disease progression is assessed every 2 cycles, for up to 40weeks, per protocol, from the date of the first dose of study drug to the date the patient is taken off study.

The primary endpoint is overall clinical benefit, expressed as the percentage of participants whose best recorded outcome meets the registry definition of complete response, partial response, or stable disease. It combines three disease-status categories rather than focusing only on tumor shrinkage. Complete response requires disappearance of measurable lesions, including bone lesions detected on bone scan, no new lesions, and no disease-related symptoms. Partial response requires more than 30% decrease in the sum of the longest diameters of measurable lesions compared with baseline. Stable disease means that changes do not meet the criteria for response or progressive disease.

Progressive disease is described using lesion growth or evidence of new lesions on imaging; the definition also includes specified bone-scan findings and certain skeletal complications. These criteria provide a structured way to classify disease status during follow-up. The endpoint is used to capture participants whose disease has not met progression criteria, including those with stable disease as well as those with response.

The registry specifies assessment every 2 cycles, for up to 40weeks, starting from the first dose and ending when a participant is taken off study. The observed number or percentage meeting the composite endpoint, the denominator used for the reported result, and any uncertainty interval are not reported in the registry record. Consequently, the endpoint definition can be described, but the trial’s estimated clinical-benefit proportion cannot be interpreted from the posted result fields.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are turned into estimates and how much uncertainty accompanies those estimates. The registry identifies the study as phase II and single group, but does not report a detailed statistical analysis plan. The statistical concepts below are general explanations of how such data are commonly described; they are not claims about analyses performed in this study.

What does a percentage endpoint represent?

For a binary endpoint such as whether a participant meets the clinical-benefit definition, the basic summary is the number meeting the definition divided by the number assessed, expressed as a percentage. The denominator matters: it may be all enrolled participants, all participants who started treatment, or a defined analysis population. Those choices can yield different estimates when participants withdraw, have incomplete follow-up, or lack an evaluable assessment. The registry record does not report the endpoint numerator, denominator, or analysis population, so the clinical-benefit percentage cannot be recovered from the posted information.

For a binary outcome, uncertainty can be described with a confidence interval around the observed proportion. In general, such an interval reflects both the observed proportion and the amount of information in the sample. It is not a guarantee that the true value lies in that interval, but a range produced by a specified method with a stated coverage level. Different interval methods can behave differently, particularly with a small sample or proportions near the extremes. No primary-outcome confidence interval or interval method is reported in the registry record.

How should a composite endpoint be understood?

The primary outcome combines complete response, partial response, and stable disease. A composite can capture several clinically distinct ways of meeting a study objective, but its overall percentage depends on the component definitions and on how each participant’s status is classified. The component counts are useful because a single combined percentage can conceal whether the total reflects responses, stable disease, or both. Component-specific primary outcome results are not reported in the registry record. The endpoint description gives criteria for response and progression, but it does not report the observed distribution across these categories.

The endpoint uses lesion measurements and imaging findings, and its timeframe includes repeated assessment during treatment. In general, an outcome assessed over time requires clear rules for the assessment window, handling of missed visits, and classification when a participant stops treatment before the planned assessment period. Those rules can affect whether a participant is considered evaluable and which status is counted. Further details about these procedures and the handling of incomplete assessments are not reported in the registry record.

What does the single-group design estimate?

A single-group study can describe outcomes observed among participants who received the intervention. It does not, on its own, estimate a randomized contrast between treatments. A before-and-after comparison may describe change within participants, but it is vulnerable to influences that change over time independently of treatment. Similarly, observed time to progression can be summarized for the group, but comparisons with an external benchmark require assumptions about how comparable the populations and follow-up processes are. No external comparator is identified in the registry record.

Open-label status means treatment assignment is known rather than masked. In general, knowledge of treatment can influence decisions about continuing treatment, additional testing, symptom reporting, and outcome classification. Objective measurement rules may reduce some subjectivity, but they do not eliminate every possible influence. Whether an independent committee reviewed outcomes, or whether reviewers were masked to other information, is not reported in the registry record.

How do time-to-event analyses differ?

Time to disease progression is listed as a secondary outcome. General time-to-event methods use both the time until an event and information from participants whose event has not been observed by the end of their follow-up. Those participants are censored rather than treated as if progression occurred at the end of observation. A survival curve can describe the estimated proportion remaining event-free over time; a median event time can be reported when the curve reaches the relevant point. Such estimates depend on appropriate follow-up and censoring assumptions. The registry record does not report a time-to-event estimate, a curve, a censoring description, or an analysis method for this outcome.

The endpoint description says disease progression is assessed every 2 cycles, for up to 40weeks, from first dose until removal from study. With periodic assessments, the exact biological time of progression may not be known; it may be identified at an assessment after progression has occurred. Statistical handling can depend on whether the analysis uses the assessment date or another convention. The registry does not report the analytic convention used. The stated assessment schedule alone is not enough to infer how progression times were calculated.

What can a sample-size calculation tell a reader?

In general, a sample-size calculation is a planning exercise based on assumptions about the endpoint, the effect worth detecting, the significance level, power, allocation, and analysis method. A planning illustration is not an observed result and does not show the probability that a completed study has demonstrated an effect. The registry record does not report the trial’s own sample-size justification or a formal power calculation. Accordingly, the enrolled group of 21 should be read as the recorded enrollment, not as proof that the study had adequate or inadequate power for its primary question.

A planning illustration based on an observed effect would also depend on a result estimate. Since the primary clinical-benefit result is not reported in the registry record, a planning calculation cannot be interpreted as a substitute for that missing result. No calculation can establish what the trial observed. The registry’s statistical analysis details, including any prespecified treatment of missing observations or choice among alternative endpoint analyses, 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("Torisel")
n      <- c(15)
events <- c(10)
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  Torisel  15  10  66.7  38.4  88.2  41.7  84.8  41.3  84.8

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, time points, or statistical comparisons. Repeated testing can increase the chance of finding at least one apparently notable result by chance. In general, protocols may address this by identifying a primary endpoint, setting a testing hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. This record identifies one primary outcome and lists time to disease progression and change in prostate-specific antigen doubling time as secondary outcomes. Any multiplicity adjustment, testing hierarchy, or interpretation plan is not reported in the registry record.

The registry does not report the primary outcome estimate or analysis results for the listed secondary outcomes. It therefore is not possible to assess whether results were selected from multiple analyses, whether testing was adjusted, or how secondary outcomes were interpreted. The number of outcome measures listed is 3, but the record does not provide analysis results for them.

Missing-data methods are important when participants withdraw, stop treatment, miss assessments, or cannot be classified at an endpoint visit. In general, excluding participants with missing outcomes can alter an estimate if those participants differ systematically from participants with complete data. Other approaches make assumptions about unobserved outcomes and should be reported transparently. The registry does not describe the amount of missing endpoint data, reasons for missingness, imputation, or sensitivity analyses.

The record also does not identify an intention-to-treat, per-protocol, safety, or other analysis population for the primary endpoint. Without the denominator and population definition, the scope of any intended estimate is unclear. These omissions do not establish that missing data or multiplicity were mishandled; they mean the registry record does not provide enough information to judge those aspects of the analysis.

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: pain (19.0%), pneumonia (14.3%), urinary tract infection (9.5%), weakness (9.5%), anemia (4.8%).

The adverse-event record lists 21 participants at risk for serious adverse events and 11 affected in the serious adverse-event field. This is a participant count in the posted safety record; it is not an estimate of the fraction of events caused by temsirolimus. The record also lists serious-event terms with percentages: pain, 19.0%; pneumonia, 14.3%; urinary tract infection, 9.5%; weakness, 9.5%; Anemia, 4.8%; and Acute Arterial ischemia, 4.8%.

These term-specific percentages should not be added together to obtain a total. A participant may have experienced more than one event, and the record does not state that the event categories are mutually exclusive. The registry entries do not provide the event counts for each term, the timing or duration of events, severity grading, or whether investigators considered an event related to treatment. Those details are not reported in the registry record.

The record lists 21 at risk and 21 affected in its other adverse-event fields, but does not provide enough detail in the posted summary to interpret that entry as a treatment-caused outcome. The deaths field is empty; deaths are not reported in the registry record, which is not the same as a reported count of zero. Safety summaries describe observed events in this study group and cannot, without a suitable comparison and fuller context, determine how much risk is attributable to treatment.

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

The registry record establishes that this was a completed, open-label phase II study of single-agent temsirolimus in chemotherapy-naïve patients with castration-resistant prostate cancer. It records 21 enrolled participants and defines overall clinical benefit as complete response, partial response, or stable disease. It also provides a timeframe for progression assessment and lists selected serious adverse-event entries.

The record does not report the primary endpoint result. It is therefore not possible to state the proportion of participants who experienced clinical benefit, describe the observed response pattern, or quantify uncertainty around the primary endpoint. The listed secondary outcomes also have no reported results. Absence of these results from the registry record is not evidence that an outcome was either favorable or unfavorable.

Even a reported result from this single-group study would describe outcomes within the enrolled group rather than establish a comparative treatment effect. The design has no randomized control arm, and the study is open label. Differences from outcomes in another population or historical experience could reflect differences in participant characteristics, follow-up, outcome assessment, or other factors, as well as treatment. The registry record does not describe a comparator suitable for estimating what would have happened to the same population under an alternative.

The adverse-event entries show that serious events were recorded among participants, including the listed terms and percentages. They do not by themselves establish causation or allow a complete assessment of safety. Interpretation would require context such as event timing, attribution, severity, and the relationship between participants and event counts; these details are not reported in the registry record.

The defensible conclusion is limited: the record describes a clinical question and a study design, but does not contain the primary efficacy result needed to answer that question quantitatively. It also does not support a treatment-versus-control claim. Any judgment about the size, precision, or comparative meaning of the clinical-benefit estimate would go beyond the results reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is a composite that combines tumor response with stable disease. Such an endpoint can be relevant to the study’s stated question, but it depends on explicit classification rules and a clear account of how each participant was assessed. The registry describes response and progression criteria, yet does not report the resulting participant counts. The distinction between a well-defined endpoint and a reported endpoint result is essential: a definition alone does not show what occurred in the study.

The single-group design also makes the estimand—the quantity the study seeks to describe—important. The primary question is about the percentage meeting the clinical-benefit definition among treated participants, not a comparative effect against a control group. Without a comparator, an observed outcome would be descriptive and would not isolate the effect of treatment from other influences. This distinction helps prevent an within-group observation from being read as proof of comparative efficacy.

The registry additionally lists time to disease progression and change in prostate-specific antigen doubling time. These outcomes involve different statistical questions from a binary clinical-benefit proportion: time-to-event analysis must account for follow-up and censoring, while a before-and-after measure requires defined assessment times and handling of incomplete pairs. Their results and analytic procedures are not reported in the registry record.

Finally, the entry illustrates why reporting should include outcome counts, denominators, uncertainty estimates, analysis populations, and methods for missing observations. Without these, readers cannot evaluate precision, robustness, or the impact of incomplete follow-up. The study design and endpoint definitions remain interpretable, but the absent primary result prevents a quantitative assessment of what the enrolled participants experienced.

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 central limitation for interpreting this trial from the registry record is that no primary clinical-benefit result is reported. There is no endpoint numerator, denominator, estimate, or confidence interval. Without those elements, neither the observed frequency of benefit nor the precision of that estimate can be evaluated.

The study has a single-group, open-label design and no separate comparator. As a result, it cannot provide a randomized estimate of the difference between temsirolimus and another treatment. Open-label outcome assessment and decisions about discontinuation may also be relevant, but the record does not describe independent review, masking of outcome assessors, or procedures intended to reduce assessment bias.

The endpoint definition is detailed, but the registry does not report the observed component outcomes or how participants with incomplete follow-up were classified. The listed assessment schedule—every 2 cycles, for up to 40weeks—does not specify how missed or delayed assessments were handled in analysis. Missing-data methods and analysis populations are not reported in the registry record.

The secondary outcomes are named but their results and methods are absent. There is no reported time-to-event estimate or account of censoring, and no reported before-and-after result for prostate-specific antigen doubling time. A sample-size justification, statistical analysis plan, interim analysis details, and multiplicity procedures are also not reported in the registry record. These gaps limit appraisal of both the planned statistical approach and the results, without proving that particular procedures were or were not used.

Safety interpretation is limited by selected event terms and percentages without full detail about timing, severity, attribution, overlap, or event-level counts. The death field is not populated. These limitations mean that the registry record supports only a partial account of the trial’s outcomes and safety experience.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Single Agent Temsirolimus (Torisel®) in Chemotherapy-naïve Castration-Resistant Prostate Cancer Patients — NCT00919035.
• Registry record last updated 2014-06-30; status last verified 2014-06.
• Results first posted 2014-04-07.
• 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

NCT00919035 is a completed phase II, open-label, single-group study sponsored by Oncology Specialists, S.C. It enrolled 21 chemotherapy-naïve patients with castration-resistant prostate cancer. The intervention was single-agent temsirolimus (Torisel®), described as 25 mg weekly. The registry lists a start date of 2009-06 and primary completion date of 2013-02.

The primary outcome was overall clinical benefit, defined as complete response, partial response, or stable disease, with progression assessed every 2 cycles, for up to 40weeks. Secondary outcomes were time to disease progression and change in prostate-specific antigen doubling time before and after treatment. The registry record does not report results for these efficacy outcomes or a detailed statistical analysis plan. It lists selected serious adverse-event entries, including 11 affected participants among 21 at risk in the serious-event field. The record does not report a primary efficacy estimate or its precision.