Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel (NCT01253642), a na phase 2 study. The primary outcome is Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%.

2. Clinical Question

The study rationale described phenelzine sulfate as a monoamine oxidase A inhibitor and proposed combining it with docetaxel in patients whose disease was progressing during or after docetaxel therapy. That rationale is a biological and clinical motivation, not evidence that the combination improved outcomes. The listed secondary outcomes included progression-free survival after treatment initiation, PSA change, response in measurable disease, time to death from all causes, toxicity, and biomarker measures. Results for those outcomes are not reported in the registry record. Because the study had no separate comparator, any observed changes in a single group would describe outcomes during treatment, not establish what would have happened to similar patients under another treatment strategy.

3. Trial Design

This was a phase II, single-group study with no masking. The registry lists allocation as not applicable and enrollment as 11. The sponsor was OHSU Knight Cancer Institute. The study started on 2010-07-12, had a primary completion date of 2016-09-15, and is listed as terminated. The reason for termination is not reported in the registry record.

Participants received phenelzine sulfate together with docetaxel. The treatment description specifies oral phenelzine sulfate once daily on days -7 to -4, followed by twice-daily dosing on days -3 to 21. Docetaxel was given intravenously over 60 minutes on day 1. Cycles were to repeat every 21 days for at least 12 weeks in the absence of disease progression or unacceptable toxicity. This describes the planned regimen; the registry record does not report the number of participants who started treatment, how many completed treatment, or how closely treatment followed the regimen.

The primary endpoint was a PSA response: a reduction of at least 30% from baseline within 12 weeks, confirmed on a second measurement at least 3 weeks later. The registry also listed secondary outcomes spanning disease control, survival, safety, and biological markers. These included response by RECIST criteria in measurable disease and MAOA expression in tumor and circulating tumor cells.

A single-group design can describe what occurred among treated participants, but it cannot directly compare their outcomes with outcomes under a different treatment. The absence of masking also means that treatment assignment was not concealed from participants or investigators. The registry record does not report the statistical analysis plan, methods for dealing with missing observations, or the analysis populations. It lists zero analyses, and the primary endpoint result is 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.

Population: 11 subjects received combination therapy

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%, measured over Within 12 weeks.

The primary endpoint counts participants who met a specified PSA response definition. A response required a decline of at least 30% from baseline within 12 weeks, followed by confirmation on a second measurement at least 3 weeks later. Requiring confirmation helps distinguish a sustained PSA change from a measurement that may not persist. The endpoint is binary at the participant level: a participant either meets the stated definition or does not, based on the available measurements and the timing rule.

PSA is a blood marker used in prostate cancer assessment. A change in PSA can provide information about disease activity during treatment, which makes it a practical endpoint for a study focused on patients with prostate cancer. However, a PSA response is not identical to a measure of tumor shrinkage, symptom improvement, or longer survival. The registry separately listed response in measurable disease, progression-free survival, and time to death from all causes as secondary outcomes.

The endpoint result itself is not reported in the registry record. The record therefore does not establish how many participants met the response definition or the precision of any estimated response proportion. Nor does the endpoint definition alone establish that a PSA change was caused by treatment: in this single-group study, there is no concurrent comparison group to separate treatment-associated changes from other possible explanations.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group study estimate?

In a single-group study, participants receive the study regimen and outcomes are described among those participants. For a binary endpoint such as the stated PSA response, the basic estimate would be the number meeting the definition relative to the number included in the endpoint analysis. The registry record reports enrollment but does not report the primary endpoint count, the analysis denominator, or an analysis result. It is therefore not possible to interpret a response estimate from this record.

General statistical explanation: an estimate from a small group can vary substantially from one set of participants to another. A confidence interval, when reported, describes uncertainty around an estimate under the assumptions of the analysis. It does not remove limitations from missing data, endpoint measurement, selection of participants, or the absence of a comparator. No primary endpoint confidence interval is reported in the registry record.

Why does confirmation matter?

The endpoint requires a PSA decline of at least 30% from baseline within 12 weeks and confirmation by a second measurement at least 3 weeks later. Confirmation makes the endpoint more specific about persistence: a single qualifying measurement is not enough. It also creates a practical requirement for follow-up. Participants without the relevant repeat measurement may not be classifiable under the stated rule, depending on the analysis method. The registry record does not report how such cases were handled or how many participants had the measurements needed for classification.

What can the design say about treatment effects?

General statistical explanation: a concurrent comparison group helps distinguish outcomes associated with a treatment strategy from outcomes that might have occurred under another strategy. Randomization, when used, helps make the groups comparable on average with respect to both measured and unmeasured factors. This study is registered as single group, with allocation not applicable. It therefore cannot directly estimate a between-group treatment contrast. A change observed within a treated group is not, by itself, a randomized estimate of the treatment effect.

The registry lists no masking. This means the study was not blinded, but the record does not specify how knowledge of treatment might have influenced particular assessments or decisions. The primary endpoint is based on PSA measurements, which are more objective than some subjective outcomes, but the record does not describe laboratory procedures, assessment schedules beyond the endpoint timing rule, or quality-control methods.

What do the planning assumptions mean?

The record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of an observed effect. It specifies that time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not a description of this trial’s single-group design. Sample-size illustrations are not observed power and do not show that the trial had a particular probability of detecting an effect. The registry record does not report the original sample-size justification, and no numerical planning estimates are stated in the registry record.

General statistical explanation: planning calculations depend on assumptions about the outcome, effect size, variability, significance threshold, and analysis design. If those assumptions differ from what is observed, the planning illustration may not represent the eventual study. A calculation based on an observed effect also cannot make a result more reliable or repair the limitations of a small, uncontrolled study.

How should secondary outcomes be understood?

The registry lists several secondary outcomes, including progression-free survival, response in measurable disease by RECIST criteria, maximum PSA change, time to death from all causes, toxicity, and biological measures related to MAOA and HIF-1alpha. Each outcome answers a different question and may require its own definition, time origin, assessment schedule, and analysis method. The registry record does not report the detailed statistical methods for these outcomes or their results.

General statistical explanation: evaluating several outcomes can create multiplicity. If many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of the tests. The registry record does not report whether multiplicity adjustments or a hierarchy of outcomes were planned. It also does not report interim analyses, a statistical analysis plan, or a justification for the enrollment target. Without those details and the outcome data, the reader cannot reconstruct or independently assess the intended inferential procedure.

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("Combination Phenelzine and Docetaxel")
n      <- c(11)
events <- c(2)
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  Combination Phenelzine and Docetaxel  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including PSA change, measurable-disease response, progression-free survival, time to death, toxicity, and biomarker measures. Considering multiple outcomes raises a general statistical issue: the more hypotheses examined, the more opportunities there may be for a result to appear noteworthy by chance. A prespecified hierarchy or adjustment can address aspects of that issue, but such methods are not reported in the registry record. The statistical analysis plan and any interim analyses are also not reported in the registry record.

Missing endpoint data could affect the response estimate because the primary definition requires a baseline assessment, a qualifying decline within 12 weeks, and a confirming measurement at least 3 weeks later. The record does not report how missing measurements, incomplete follow-up, treatment discontinuation, or participants without confirmation were handled. It also does not report the number evaluable for the primary endpoint or define an analysis population.

Enrollment was 11, but the record does not establish that all enrolled participants contributed to every outcome. Without information on treatment initiation, follow-up, and endpoint availability, enrollment cannot be treated as the analysis denominator. The record does not report whether analyses were based on all enrolled participants, treated participants, or a subset with adequate measurements. These gaps limit interpretation of both the potential response estimate and its uncertainty.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sudden death (9.1%).

The registry’s safety figures list 11 participants at risk for serious adverse events and 1 affected by a serious adverse event in the combination group. Sudden death is listed among the serious adverse event terms at 9.1%. The record also lists 11 participants at risk for other adverse events and 11 affected, and records 11 deaths.

These figures require caution. The registry record does not report the observation period for these counts, event-level details, the timing of events, or whether the serious adverse events or deaths were judged related to treatment. The serious adverse event term and percentage do not, on their own, establish causality. The record also does not explain the relationship between the recorded deaths and the listed adverse event categories. It would be inappropriate to infer that the combination caused the deaths or that each death occurred during a particular period based on these figures alone.

The study has no separate comparison group, so the reported counts cannot be contrasted with a concurrent control group. The registry record does not provide enough detail to assess how the safety events were collected or classified. These figures describe what the registry lists; they do not by themselves establish the regimen’s comparative safety.

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

The registry record identifies a focused clinical question: whether patients with prostate cancer progressing after first-line docetaxel experienced a confirmed PSA decline during treatment with phenelzine sulfate and docetaxel. It also records a phase II, single-group study, the planned regimen, an enrollment of 11, and a primary endpoint definition. Those details help identify the intended population, treatment, and outcome.

The record does not report the primary endpoint result. It therefore does not establish how many participants met the PSA response definition, how large a response proportion might have been, or how precisely such a proportion could be estimated. The listed secondary outcomes also lack reported results in the registry record. The study’s status as terminated is recorded, but the reason for termination is not reported in the registry record and should not be inferred.

Even if a single-group response result were available, it would describe outcomes among participants receiving the combination rather than prove what the combination caused. Without a concurrent control group, it would be difficult to separate treatment-associated changes from other influences on disease course or measurement. A PSA response is also distinct from outcomes such as tumor response, progression-free survival, overall survival, or toxicity; the registry lists these as separate questions.

Accordingly, this record can inform readers about the study’s design and the outcome it set out to assess, but it cannot support a conclusion about the combination’s efficacy. The absence of a reported result is not evidence of no response, just as the proposed biological rationale is not evidence of benefit. The safety figures should likewise be read as registry counts with important details, including attribution and observation period, not reported.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is concrete while its available outcome reporting is incomplete. The endpoint specifies a meaningful operational rule: a PSA reduction of at least 30% within 12 weeks, confirmed by another measurement at least 3 weeks later. That precision clarifies what would count as a response, but a definition alone cannot answer how often responses occurred. The primary result is not reported in the registry record.

The design also illustrates the difference between describing outcomes and estimating a treatment effect. A single-group study can document the course of participants receiving a regimen. Without a concurrent comparator, it cannot provide a direct estimate of how outcomes differ under another treatment strategy. This distinction matters especially when an intervention is studied in a setting where the disease is already progressing after prior therapy.

The record further underscores why enrollment and analysis size should not be treated as interchangeable. Enrollment was 11, but the number included in the primary endpoint analysis is not reported. The endpoint’s confirmation rule requires follow-up measurements, and the registry does not describe missing-data handling. Those details would be necessary to understand the denominator and uncertainty of any response estimate.

Finally, the record lists safety events and numerous secondary outcomes, but does not provide the methods and results needed for a complete statistical assessment. Sample-size planning illustrations are not observed power, and they do not substitute for a reported outcome analysis. The central lesson is that a registered study question, a specified endpoint, and a recorded safety count each provide different kinds of information; none should be mistaken for a complete estimate of efficacy or comparative safety.

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.

Several limitations are specific to this study record. It describes a single-group design with no separate comparator, so the study cannot directly estimate a treatment contrast. The lack of masking is recorded, but the registry does not describe how outcome assessment or treatment decisions were protected from potential influence. The study is listed as terminated, while the reason for termination is not reported in the registry record.

Enrollment was 11, and the primary endpoint result and analysis denominator are not reported. The endpoint requires follow-up and confirmation, yet the record does not state how many participants had complete measurements or how missing measurements were handled. This prevents assessment of endpoint completeness and the precision of a response estimate.

The record lists secondary outcomes covering disease response, survival, toxicity, and biomarkers, but does not report their results or detailed analysis methods. It does not report the statistical analysis plan, interim analyses, original sample-size justification, or multiplicity strategy. The safety counts lack reported information about event timing, follow-up period, and attribution to treatment. These omissions limit interpretation of both efficacy and safety; they do not establish that an outcome was favorable or unfavorable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phenelzine Sulfate and Docetaxel in Treating Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel — NCT01253642.
• Registry record last updated 2019-10-02; status last verified 2019-09.
• Results first posted 2017-12-11.
• 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

This terminated phase II study evaluated phenelzine sulfate with docetaxel in patients with prostate cancer progressing after first-line docetaxel. It was an unmasked, single-group study with enrollment of 11. The primary endpoint was a confirmed PSA decline of at least 30% from baseline within 12 weeks, with confirmation at least 3 weeks later.

The registry record lists secondary outcomes for disease response, PSA change, progression-free survival, time to death, toxicity, and biomarkers. The primary endpoint result, secondary outcome results, analysis populations, and detailed statistical analysis plan are not reported in the registry record. The reason for termination is also not reported.