A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer (NCT01084759), a na na study. The primary outcome is Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline..

2. Clinical Question

Statistically, the central question is a single-group estimation question: how often did participants meet the specified endpoint under the study’s treatment plan? Without a comparator group, the design does not directly estimate a difference between treatments. A percentage from a single group can describe the observed participants, while its uncertainty depends on the number of participants and the number meeting the endpoint. The registry records 16 enrolled participants, but does not report the primary endpoint count or percentage. It also does not report a confidence interval for that endpoint in the information available in the registry record.

The clinical question includes both whether participants remained on therapy for the stated period and whether their PSA was below baseline. Those components should not be treated as interchangeable: a participant would need to satisfy the endpoint’s stated completion and PSA conditions. The outcome is therefore not simply a measure of treatment exposure, nor does the endpoint alone establish how other clinical measures changed.

3. Trial Design

This is a completed, single-group pilot study with enrollment of 16 participants. The registry lists the phase as NA, allocation as NA, and masking as none. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The record gives a start date of 2010-03 and a primary completion date of 2014-10. These dates describe the registry entry; they do not establish the timing of each participant’s treatment or follow-up.

The treatment plan described in the record combines testosterone cypionate injections with oral etoposide. The described testosterone schedule is an intramuscular dose of 400 mg every month for a total of 3 injections. Oral etoposide is described as 100 mg/day in divided doses, with 50 mg every 12 hours for 14 days out of 28 days per cycle, beginning on the day of the testosterone injection. Eligible participants were to continue androgen-ablative therapy with an LHRH agonist if they had not been surgically castrated. The record does not fully describe every detail of treatment delivery in the arm description, so the brief summary is the source for these schedule details.

The study plan describes repeat PSA testing and bone/CT scans after 3 months to assess the effect of combined treatment on those parameters. It also describes stopping study treatment for participants with sustained PSA elevations at least 50% above the pre-testosterone treatment level after the initial 3 months. The available brief summary ends partway through a sentence about participants with PSA levels below a threshold; the remainder of that rule is not reported in the registry record.

With one group and no masking, the design is descriptive and exploratory rather than a randomized comparison. The record does not report a control arm, a randomized allocation procedure, or a masking procedure. It does not report the protocol’s sample-size justification or a detailed statistical analysis plan. The registry lists 3 outcome measures and 0 analyses, but that does not establish whether analyses were conducted outside the registry entry. The primary endpoint is a percentage of participants meeting a binary definition, while a secondary outcome concerns participants with a RECIST response. Results for those outcomes 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 Percentage of Patients Completing at Least 3 Months of Therapy With a PSA Below Baseline., measured over 3 months.

The primary endpoint is the percentage of participants completing at least 3 months of therapy with a PSA below baseline. It is measured at the stated 3-month timeframe and combines two conditions: completing the specified treatment period and having a PSA value below the baseline value. The registry labels the parameter as a number and the unit as percentage of participants. No observed number or percentage meeting the endpoint is reported in the registry record.

As a statistical outcome, this is binary at the participant level: each participant either meets the full definition or does not. A percentage expresses the number meeting the definition relative to the relevant participant group. That makes the measure straightforward to describe, but interpretation requires knowing the endpoint count, the denominator included in the analysis, and how missing PSA values or incomplete treatment were handled. Those details are not reported in the registry record.

In general, a threshold-based endpoint can make a study question operational by defining what counts as meeting the stated criterion. It can also discard information about the size of changes: participants just on either side of a threshold may be classified differently, while different values on the same side receive the same classification. Here, the endpoint is specific to treatment completion and PSA relative to baseline. It does not by itself summarize the scans, RECIST response, safety outcomes, or any other clinical outcome. The record’s primary endpoint definition should therefore be read as a particular measure, not as a complete account of participant outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record defines a percentage endpoint and identifies a 95% confidence interval as its dispersion measure. It does not report the endpoint estimate, interval limits, or the specific statistical method used to calculate the interval. The explanations below are general statistical context, not claims about methods used in this study.

What a percentage estimates

For a binary endpoint, each participant is classified according to whether the endpoint definition is met. The percentage is a summary of the share meeting the definition in the analysis group. To interpret it, readers need both the event count and the denominator. The denominator may not always equal enrollment: participants can sometimes be excluded from a particular analysis or have outcome information unavailable. The registry record does not state the primary endpoint count, analysis denominator, or analysis population, so none should be inferred from enrollment alone.

A percentage compresses the participant-level information into one summary. It does not show the range of individual PSA values, the extent of change for each participant, or why some participants might not meet the endpoint. In this trial, it also includes completion of at least 3 months of therapy, so it reflects both the stated duration condition and PSA status. The primary endpoint’s exact definition should guide interpretation rather than treating the measure as a general response rate.

What a confidence interval means

In general, a confidence interval represents uncertainty around an estimate under a particular statistical model and procedure. It is not a guarantee that the true value lies within the interval, nor does it describe the range of individual participant outcomes. An interval for a percentage is particularly useful when the number of participants is limited, because the same observed percentage can carry different levels of uncertainty depending on the denominator. In this record, the interval is named as the intended dispersion measure, but its limits and calculation method are not reported.

Different interval procedures can behave differently, especially when the denominator is small or the observed proportion is near an endpoint of its possible range. The registry record does not identify the procedure, so it is not possible to assess whether a particular method was used or to reproduce the interval. No interval should be reconstructed from the enrollment count because the endpoint event count is not reported.

Single-group estimation and comparison

General statistical interpretation distinguishes estimation within a group from comparison between groups. A single-group percentage estimates how often an outcome occurred in that group under the study conditions. A randomized comparison can estimate a between-group contrast while helping balance some sources of difference between groups. This study is recorded as single group, with allocation listed as NA, so there is no treatment contrast to estimate from a concurrent control arm. The design cannot establish that any observed change was caused by the combination rather than other influences.

That limitation should not be confused with uncertainty in a percentage. Sampling uncertainty concerns how precisely the group estimate is known. Lack of a comparator concerns whether the design can attribute a difference or change to treatment. A narrow interval, if one had been reported, would not solve the absence of a control group; a comparator would not by itself resolve missing endpoint data or other measurement concerns.

Over-dispersion and model choice

In general, over-dispersion means that observed variability is greater than a model assumes. It is relevant when a statistical model imposes a particular variance structure, because underestimated variability can make uncertainty appear too small. This registry record does not report a model for the primary binary endpoint, evidence of over-dispersion, or a model-based analysis. Accordingly, over-dispersion is a general concept rather than a documented feature of this study.

For a simple binary percentage, the main questions include the endpoint definition, denominator, event count, and interval method. More complex models may be used when outcomes depend on covariates, clustering, repeated observations, or differing follow-up, but the registry does not report such an analysis for the primary endpoint. Readers should not assume adjustment, subgroup analysis, or repeated-measures modeling absent a reported plan or result.

Planning illustrations are not observed power

In general, sample-size planning asks how many participants might be needed under specified assumptions about the anticipated effect, variability, significance level, and desired power. A planning illustration based on an observed effect is retrospective and should not be mistaken for the trial’s original design rationale or for observed power. The registry record states that any planning illustration is computed from the observed effect, uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. It also distinguishes total events for time-to-event illustrations from participants per arm for other illustrations.

Those assumptions do not describe this trial’s design: the study is single group, not an equal-allocation two-arm comparison. The protocol’s own sample-size justification is not reported in the registry record. No planning sample size should be read as the number enrolled or as evidence that the study had a particular probability of detecting an effect. Such calculations are illustrations conditional on assumptions, while the observed enrollment is 16.

Finally, the registry’s count of 0 analyses means that no analysis entries are recorded in the registry summary. It does not establish that no analysis was done elsewhere. The analysis methods, handling of missing data, and population used for the primary endpoint 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("Treatment Group")
n      <- c(14)
events <- c(6)
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  Treatment Group  14  6  42.9  17.7  71.1  21.4  67.4  21.3  67.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including the primary percentage endpoint and the secondary outcome of participants with a RECIST complete or partial response. It does not report a multiplicity strategy describing whether or how statistical testing across outcomes was controlled. In general, when several outcomes are examined, the chance of at least one apparently notable finding can increase if each is treated as an independent confirmatory test. Whether that issue applies, and how it was handled, cannot be established from the registry record.

The primary endpoint result is not reported in the registry record, and the registry does not state the number of participants with missing primary endpoint information. It also does not describe whether incomplete treatment, missing PSA measurements, or other unavailable observations were counted as not meeting the endpoint, excluded, or handled by another rule. These choices can affect the denominator and interpretation of a percentage. The registry record does not report an imputation method or sensitivity analysis.

The analysis population is also not described. The enrollment figure is 16, but the record does not say whether the endpoint analysis included all enrolled participants or a subset defined by treatment received, follow-up, or evaluability. The registry lists 0 analyses; that is a count of analysis entries, not proof that no analyses took place. A detailed statistical analysis plan, including population definitions and missing-data rules, is not reported in the registry record.

As general context, transparent reporting of outcome-specific denominators, missingness, analysis populations, and multiplicity decisions helps readers distinguish an observed estimate from assumptions used to produce it. Those details are especially important for a binary endpoint that requires both completion of a treatment period and an available PSA assessment.

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: pulmonary embolus (12.5%), neutropenic fever (6.2%).

The registry reports serious adverse events in a treatment group with 16 participants at risk and 3 affected. It lists pulmonary embolus at 12.5% and neutropenic fever at 6.2% among the leading serious terms. These are safety figures and should be read separately from the PSA-based primary endpoint.

The listed percentages describe the recorded serious-event terms; they are not treatment-versus-control comparisons. The study has a single group, so the registry does not supply a concurrent comparator for assessing whether event frequencies differ from another treatment or from a control condition. The record does not report event timing, duration, outcome, attribution to treatment, or whether any participant experienced more than one serious event. Those details should not be inferred from the term percentages.

The registry also records 16 participants at risk and 16 affected in a separate other-adverse-event category. The category’s definition and event details are not stated in the information summarized in the registry record. These entries do not replace a complete safety narrative, and they do not establish the cause of an event. The figures describe what the registry records, with the limits of the available reporting.

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

The record establishes that a completed pilot study enrolled 16 participants in a single group and evaluated a combination of parenteral testosterone and oral etoposide. Its primary endpoint is defined as the percentage completing at least 3 months of therapy with PSA below baseline. This provides a clear description of the intended primary measure, but the registry does not report the observed primary endpoint result.

Consequently, the record does not permit a numerical statement about how many participants met the primary definition or how precise an estimate would be. It also does not permit interpretation of the named RECIST response outcome, whose result is not reported in the registry record. The absence of reported results is not evidence that the outcome was zero, nor is it evidence of a particular response rate.

Even a reported percentage from this design would describe participants in the treatment group, not a treatment effect relative to a control group. Because no comparator is recorded, the design cannot isolate treatment-associated changes from other explanations for changes over time. This is a limitation of what the design can establish; it is not a claim that the treatment caused, or did not cause, any particular outcome.

The serious adverse-event entries are also descriptive. The registry lists 3 of 16 participants affected, with pulmonary embolus and neutropenic fever among the leading serious terms. Without event-level context or a comparator, these entries cannot establish causality or quantify a comparative safety difference.

In general, a pilot study can describe feasibility and generate information for later study planning, but the registry record does not report a feasibility analysis or a justification for the sample size. Any sample-size planning illustration should be treated as conditional planning, not as observed power. The most defensible reading is therefore limited: the registry records a treatment plan, a defined primary endpoint, enrollment, and some serious adverse-event information, but does not report the primary outcome result or enough analysis detail for a fuller statistical conclusion.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between defining an endpoint and reporting its result. The registry gives a specific primary outcome: completion of at least 3 months of therapy with PSA below baseline. Yet the result for that outcome is not reported in the registry record. Readers can identify what was intended to be measured without being able to assess its observed frequency or precision.

The single-group design also makes the estimand important. A percentage within one group answers a descriptive question about that group. It is not a randomized treatment contrast, and it cannot by itself identify what would have happened under a different treatment or control condition. The registry lists no separate comparator, so interpretation should not turn a within-group outcome into a causal claim.

The record also illustrates why denominators, missing-data rules, and analysis populations matter for binary outcomes. The primary endpoint combines treatment completion with a PSA threshold; participants with incomplete follow-up or unavailable measurements could affect how that percentage is defined. The registry does not report the endpoint count, denominator, missing-data handling, or analysis population. Those omissions leave key components of statistical interpretation unresolved.

Finally, the safety entries show the difference between reporting event frequencies and attributing events to an intervention. The record identifies serious events but does not provide a comparator or detailed event context. In statistical reporting, estimates, uncertainty, design, and outcome definitions need to be read together. This record makes the design and endpoint visible, while leaving the primary result and several analysis details unreported.

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 study has a single treatment group, with no randomized comparator listed. This prevents a direct between-group comparison and limits what can be concluded about whether changes were attributable to the treatment combination. The allocation field is NA and masking is none, so the registry does not describe randomized allocation or blinded assessment.

Enrollment was 16, and the record identifies the study as a pilot. The registry does not report the protocol’s sample-size rationale, so it is not possible to determine what precision or effect size the study was designed to assess. A planning illustration based on an observed effect, if considered, is not the trial’s own design justification and is not observed power.

The primary endpoint result is not reported in the registry record. The record also does not report its event count, analysis denominator, confidence interval limits, analysis population, or handling of missing PSA assessments and incomplete treatment. These omissions prevent assessment of the endpoint’s observed frequency and uncertainty. The result for the secondary RECIST response outcome is also not reported.

The brief treatment description includes a plan to reassess PSA and scans after 3 months and a stopping criterion based on sustained PSA elevation. However, the available summary ends partway through its description of the rule for participants with PSA levels below a threshold. The remaining treatment-continuation details are not reported in the registry record. The record also does not describe adherence, treatment exposure by participant, or follow-up beyond the stated assessment plan.

For safety, the registry lists serious adverse-event counts and leading terms but does not report event timing, duration, attribution, outcomes, or participant-level overlap. The available information therefore supports a limited description of recorded events, not a comprehensive assessment of safety or comparative risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Study of Parenteral Testosterone and Oral Etoposide as Therapy for Men With Castration Resistant Prostate Cancer — NCT01084759.
• Registry record last updated 2016-05-09; status last verified 2016-01.
• Results first posted 2016-05-09.
• 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

The registry record describes NCT01084759, a completed, single-group pilot study in men with castration-resistant prostate cancer. It records enrollment of 16 participants, with the phase listed as NA, allocation as NA, and masking as none. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

The treatment plan combines parenteral testosterone with oral etoposide. The primary endpoint is the percentage completing at least 3 months of therapy with PSA below baseline. The record also names a secondary RECIST response outcome. Neither the primary endpoint result nor the secondary response result is reported in the registry record.

The registry lists serious adverse events affecting 3 of 16 participants, including pulmonary embolus at 12.5% and neutropenic fever at 6.2% among the leading serious terms. Analysis methods, missing-data handling, analysis populations, and the protocol’s sample-size justification are not reported in the registry record.