Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer (NCT01020305), a na phase 1, phase 2 study. The primary outcome is Reduction in Serum PSA.

2. Clinical Question

The study asked whether serum prostate-specific antigen (PSA) declined by more than 50% from baseline in male participants with castration-resistant prostate cancer (CRPC). The endpoint description sets the assessment at 16 weeks, after a stated 12 weeks of treatment. No result for this primary question is reported in the registry record, so the record does not establish how many participants met the threshold.

This is a question about a prespecified threshold in a laboratory measure, not a direct comparison of outcomes between randomized groups. Because the two drugs were used together, the study design also does not isolate the contribution of either drug to any PSA change.

3. Trial Design

This was a phase 1/phase 2, single-group study with a recorded enrollment of 5. Allocation is listed as NA, and masking as none. The registry describes one treatment group: temsirolimus with bicalutamide. Temsirolimus was administered intravenously at 25 mg once weekly for 12 weeks, while bicalutamide was administered orally at 50 mg/day.

The primary outcome was a binary measure: whether a participant had a greater than 50% reduction in serum PSA from baseline. The outcome description specifies that assessment was at 16 weeks, while the timeframe states 12 weeks of treatment with the primary outcome assessed at 16 weeks. These are distinct time points in the record; the registry does not provide further details about the interval between the end of treatment and assessment.

The study began in 2009-10, had a primary completion date of 2012-04, and is listed as terminated. The registry record does not report why the study was terminated, so termination should not be interpreted as evidence about the treatment or the outcome. The sponsor is listed as Sandy Srinivas.

A single-group design can describe outcomes among participants receiving the regimen, but it does not provide a concurrent control group for estimating what would have happened under a different treatment or without the regimen. With no masking, the study is also not recorded as blinded. The registry record does not report a detailed protocol, a sample-size justification, or the statistical analysis 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

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 Reduction in Serum PSA, measured over 12 weeks treatment, with primary outcome assessed at 16 weeks.

The primary endpoint was the proportion of participants with a greater than 50% drop in serum PSA compared with baseline, assessed at 16 weeks. PSA is the serum measure named in the registry outcome. The endpoint converts each participant’s change into a yes-or-no classification according to whether the stated threshold was met.

In general, a threshold-based endpoint can make a study question explicit and allows outcomes to be counted as participants who did or did not meet a defined criterion. It also discards information about the size of changes within either category: a smaller decline and a decline just short of the threshold are both classified as not meeting it, while different declines above the threshold share the same classification. The registry record does not report the individual PSA values or the number meeting the threshold.

The endpoint is described as a proportion, but the primary results are not reported in the registry record. There is therefore no reported proportion, effect estimate, confidence interval, or statistical test for the endpoint to interpret. The stated 12 weeks of treatment and 16-week assessment should not be conflated; the record identifies both, but does not give further measurement details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either meets the stated greater than 50% PSA-reduction threshold or does not. A natural descriptive summary for a binary endpoint is the number meeting the criterion and the total number assessed, often expressed as a proportion. The registry record does not report either the endpoint count or the primary analysis, so no observed proportion can be described.

In general, an estimate summarizes the observed data, while a confidence interval describes the statistical uncertainty around that estimate under a specified method and assumptions. A narrow interval would indicate greater precision than a wide interval. For a small group, interval estimates are especially important because the point estimate alone can give a misleading impression of certainty. The record contains no primary estimate or confidence interval, and it does not report which interval method, if any, was planned.

A p-value, in general, measures how compatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It does not measure the probability that a treatment works, and it does not indicate the size or clinical importance of an effect. No p-value or hypothesis test for the primary endpoint is reported in the registry record. Since the study has no separate comparator group, a test comparing randomized treatment arms would not describe its recorded design.

The design is single-group. A within-group description could report the number of participants meeting the endpoint, but it would not distinguish an effect of the treatment combination from changes that might occur for other reasons. In general, random assignment to concurrent groups can support a more direct treatment comparison by balancing factors across groups on average. That type of comparison is not available in this study as registered. The record does not report a planned baseline-adjusted model or other specific analysis method.

The outcome uses a threshold applied to serum PSA change. In general, turning a continuous measurement into a binary endpoint simplifies the definition of a response, but information about the magnitude and distribution of changes is lost. The registry does not report continuous PSA results or participant-level measurements, so those cannot be reconstructed or compared with the binary endpoint.

The planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not a description of the actual single-group study design. It also characterizes the sample-size exercise as a planning illustration based on an observed effect and says that the effect to detect is a stated fraction of that effect. These illustrations should be understood as hypothetical planning scenarios; they are not a report of the number of participants analyzed, and they are not observed power. The registry record does not report a sample-size justification for the trial itself.

In general, sample-size planning asks how much information a future study would need to detect a specified effect under chosen assumptions. Its answer depends on the endpoint, effect size, variability, significance level, power target, allocation, and analysis method. A planning figure does not demonstrate that an effect was observed or that a study had a particular probability of success after the data were collected. In this case, the planning assumptions describe two arms, whereas the registered design is single-group. They should not be mistaken for an analysis of this trial’s design.

The endpoint is a participant count, not a count of recurrent events per person. Over-dispersion is a general concern for some count-data models when variability exceeds a model’s assumptions; it is not a reason to reinterpret this binary participant-level endpoint as a count outcome. The registry record does not identify a statistical model, any adjustment for covariates, or a method for handling repeated measurements.

The record lists zero analyses. As a result, no inferential method can be attributed to a posted primary analysis. Details such as the analysis population, treatment of missing week-16 measurements, and handling of protocol deviations are not reported in the registry record. Without those details and an outcome result, it is not possible to assess whether the endpoint was analyzed as planned or how sensitive any finding would be to alternative assumptions.

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 + Bicalutamide")
n      <- c(3)
events <- c(0)
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 + Bicalutamide  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It identifies one outcome measure, but that fact alone does not establish whether additional outcomes, time points, subgroups, or interim looks were considered in the protocol. No interim analyses or statistical plan are reported in the registry record. There is therefore no basis for describing an adjustment for multiple testing or for assessing its effect on the primary result.

Missing-data methods and analysis populations are also not reported in the registry record. Although enrollment is recorded as 5, the record does not say how many participants completed treatment, had a week-16 assessment, or were included in a primary analysis. It does not describe how a missing PSA measurement would be classified or handled. Missing endpoint data can affect a proportion because the denominator and the assumptions about unobserved outcomes matter; in general, the amount and pattern of missingness should be reported alongside the analysis approach.

The registry lists zero analyses and does not report the primary outcome result. It also does not state whether the analysis was intended to include all enrolled participants, all participants who received treatment, or another defined population. These omissions prevent assessment of the analysis denominator and any differences between enrolled participants and those with evaluable outcomes. The reason for termination and any related analysis decisions are not reported in the registry 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: colitis (20.0%).

For the Temsirolimus + Bicalutamide group, the registry records 5 participants at risk for serious adverse events and 1 affected. For other adverse events, it records 5 at risk and 5 affected. The record lists Colitis at 20.0% among the top serious terms. These figures describe the registry’s safety entries; they do not establish whether an event was caused by treatment.

The record does not provide further detail in these entries about event timing, severity beyond the serious-event classification, recurrence, or participant-level overlap between serious and other events. The same participant may be represented in more than one event category, so the categories should not be added to create a total number of people affected. Deaths are not reported in the registry record. The safety figures should be read as descriptive counts in this small group, not as a comparison of risk against a control group.

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

The record describes a study designed to assess whether participants receiving temsirolimus with bicalutamide had a greater than 50% decrease in serum PSA by the 16-week assessment. It reports the regimen, the endpoint definition, enrollment of 5, and the study’s single-group design. It does not report the primary endpoint result, so it cannot show how many participants met the criterion or how precisely any proportion was estimated.

The absence of a reported outcome is not the same as a result of zero responses, and it does not establish that the combination did or did not produce a change. The record also cannot support a comparison with another treatment because no separate comparator group is described. Even if a PSA change had been reported, the single-group combination design would not by itself identify the effect of either drug individually or distinguish treatment effects from other explanations for change.

In general, a biomarker endpoint and a clinical outcome answer different questions. A threshold-defined PSA change is the endpoint named in this record; no additional clinical outcomes or results should be inferred from it. The registry does not report longer-term outcomes or further follow-up details for the primary measure.

The terminated status is a record status, not an explanation for why the study ended. The reason for termination is not reported in the registry record, and it should not be interpreted as proof of either benefit, lack of benefit, or a safety problem. The posted information is therefore most useful for understanding the study question and design, while leaving the central outcome unresolved.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between a clearly defined endpoint and a reported result. The registry states a binary criterion—a greater than 50% serum PSA drop—and gives an assessment time, but it does not report the number meeting that criterion or an analysis. Defining an endpoint does not, by itself, provide evidence about its observed frequency or precision.

The recorded enrollment of 5 also makes the importance of denominators and uncertainty apparent. In general, a small dataset provides limited information, and estimates from it can be sensitive to individual observations. Reporting an outcome count together with an uncertainty interval would help readers understand how much precision the data support. Neither is present for the primary endpoint in the registry record.

The single-group design is another central statistical feature. It can describe outcomes among participants receiving a combination regimen, but it does not furnish a concurrent treatment comparison. A combination also prevents attribution of any observed change to one component alone. These are design limits, not conclusions about whether the regimen changed PSA.

Finally, the planning assumptions describe an equal-allocation, two-arm illustration, while the registered study is single-group. Keeping planning scenarios separate from the actual design and from observed results is essential: a planning calculation is not evidence that an effect occurred, and it is not observed power. The record’s missing outcome and analysis details therefore matter as much as its endpoint definition when assessing what can be concluded.

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 most direct limitation for interpretation is that the primary outcome result is not reported in the registry record. There is no count of participants meeting the PSA threshold, no reported estimate, and no uncertainty interval. Although enrollment is 5, the number with an evaluable week-16 result is not reported, so the endpoint denominator is unknown.

The registered single-group design has no separate comparator, and allocation is marked NA. Masking is listed as none. Accordingly, the design does not provide a randomized, masked comparison with which to estimate a relative treatment effect. Because temsirolimus and bicalutamide were administered together, it also cannot separate their individual contributions.

The record gives a 12-week treatment timeframe and a primary assessment at 16 weeks but does not provide additional measurement or follow-up details. The reason for termination is not reported in the registry record. Nor are the protocol, sample-size justification, analysis plan, analysis population, missing-data approach, or multiplicity handling reported. These omissions limit assessment of how the primary outcome was intended to be analyzed and why the study ended.

The planning assumptions describe two-arm scenarios, which do not match the registered single-group design. Those illustrations should not be used to fill the missing trial results or to imply observed power. Together, the absent primary analysis, small recorded enrollment, and lack of a comparator constrain what can be inferred from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer — NCT01020305.
• Registry record last updated 2014-10-13; status last verified 2014-10.
• Results first posted 2014-10-13.
• 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

NCT01020305 is a phase 1/phase 2, single-group study of temsirolimus with bicalutamide in male participants with castration-resistant prostate cancer. The recorded enrollment is 5. Temsirolimus was administered intravenously at 25 mg once weekly for 12 weeks, with bicalutamide administered orally at 50 mg/day.

The primary endpoint was a greater than 50% reduction in serum PSA from baseline, assessed at 16 weeks. The study began in 2009-10, has a primary completion date of 2012-04, and is listed as terminated. The registry record does not report the primary outcome result, the reason for termination, or a primary analysis. It lists 1 serious adverse event affected among 5 at risk, 5 other adverse events affected among 5 at risk, and Colitis at 20.0% among the top serious terms; deaths are not reported in the registry record.