Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer (NCT00330161), a na phase 2 study. The primary outcome is Proportion of Patients Who do Not Demonstrate Disease Progression.

2. Clinical Question

3. Trial Design

NCT00330161 is a phase II, single-group trial sponsored by the National Cancer Institute (NCI). Its title concerns vorinostat in patients with progressive metastatic prostate cancer; the official title specifies advanced prostate cancer that progressed on one prior chemotherapy. Enrollment was 29. The registry lists recurrent prostate cancer and stage IV prostate cancer among the conditions.

There was no randomized allocation and no masking. With one treatment group and no comparator, the design can describe outcomes among participants receiving vorinostat, but it cannot make a direct randomized comparison with another treatment or a control condition. The absence of a control group also means that changes or events observed during treatment cannot by themselves establish what would have happened in a different treatment setting.

The arm description specifies oral vorinostat once daily on days 1-21, with courses repeating every 21 days. Treatment was planned to continue for at least 4 courses in the absence of disease progression or unacceptable toxicity. The description also states that participants achieving complete response after 4 courses would receive an additional 3 courses. The brief summary additionally lists laboratory biomarker analysis as an intervention, but no biomarker findings are reported in the registry record.

The registry gives a start date of 2006-03, primary completion of 2009-09, and status of completed. The primary endpoint was framed around disease progression at 6 months. The record states that all eligible patients were off therapy before that time point, so it does not present an endpoint result at the planned time. Details such as the full eligibility criteria, participant flow beyond the stated reasons for leaving therapy, and the final analysis population 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

Analysis population for the primary outcome, as defined in the registry: The primary objective was to determine the number of patients wtih progression-free survival at 6 months. Unfortunately all eligible patients were off therapy before the 6 month time point. 13 (48%) were removed due to progression, 11 (41%) secondary to toxicity, and 3 (11%) for other reasons.

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: Of the 29 patients enrolled, only 27 were analyzed. Two patients were deemed ineligible after treatment started and they were excluded from all analysis except adverse event collection.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients Who do Not Demonstrate Disease Progression, measured over At 6 months.

The primary endpoint asks what proportion of patients did not demonstrate disease progression at 6 months. This is a time-specific disease-control question: it focuses on whether participants were progression-free at a defined follow-up point, rather than reporting only an event count or a response measured at any time during treatment.

Such an endpoint is useful in a trial of progressive disease because it places attention on the duration for which progression has not been observed. Its interpretation depends on how progression is defined, how it is assessed, and how participants without a documented assessment at the specified time are handled. Those details are not reported in the registry record.

The registry states that all eligible patients were off therapy before the six-month time point. It lists removal due to progression for 13 (48%), secondary to toxicity for 11 (41%), and for other reasons for 3 (11%). Leaving treatment before the assessment time is not itself a complete endpoint result: discontinuation for toxicity or another reason does not establish whether progression had occurred by 6 months. The record does not report a six-month proportion, an estimate of uncertainty, or a detailed method for classifying participants who left therapy before the endpoint assessment.

The endpoint description mentions Fisher's Exact Test. However, a test result, reference proportion or comparison group is not reported in the registry record. Therefore, the planned test description should not be mistaken for a reported statistical finding.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial is described as phase II and single-group, with no masking and no randomized allocation. This design determines what statistical questions can be answered. A single-group study can report the observed outcomes in its treated participants. Without a concurrent comparator, it cannot estimate a randomized difference between vorinostat and another treatment or control condition. This limitation applies even if an outcome is measured precisely within the study cohort.

What does the primary endpoint measure?

The primary endpoint is the proportion of patients who did not demonstrate disease progression at 6 months. A proportion is a count of participants meeting a defined condition relative to a defined analysis population. Its interpretation depends on the denominator, the progression criteria, and how missing or incomplete follow-up is handled. The registry record does not report those operational details or a final estimate for this endpoint.

For a time-specific endpoint, the assessment time matters. A participant who leaves treatment before the assessment may still have an outcome that can be classified, but the classification requires follow-up and a prespecified rule. Leaving treatment because of toxicity or another reason is not automatically equivalent to progression, and it is not automatically equivalent to remaining progression-free. The record says all eligible patients were off therapy before 6 months, but does not describe how their status at 6 months was determined.

What can Fisher's Exact Test tell readers?

The primary endpoint description says Fisher's Exact Test will be used. In general, this test evaluates evidence of association between categorical outcomes and groups, or can be used to compare a categorical outcome with a specified reference distribution. It is often considered when data are expressed as counts in categories. A test result needs a clearly defined comparison, the relevant counts, and an analysis population. The record does not report a comparator, a reference proportion, a test statistic, or a p-value. The mention of a test is therefore a statement about a planned method, not a result.

A p-value, in general, describes how compatible observed data are with a specified null model under the assumptions of the test. It is not a measure of the size or clinical importance of an effect, and it does not replace an estimate with an interval. No p-value is reported for the primary endpoint in the registry record, so no inference from such a value can be made.

How should uncertainty be assessed?

A confidence interval, in general, expresses the range of values compatible with the data and a stated statistical procedure. It communicates precision as well as the direction and scale of an estimate. A narrow interval indicates greater precision than a wide interval, but neither alone resolves design limitations such as the lack of a comparison group. The registry record does not report a confidence interval for the primary endpoint or the listed secondary outcomes.

Planning sample sizes are distinct from observed results. A planning illustration can describe assumptions under which a future study might be designed; it is not an outcome of this trial and is not observed power. The registry record does not report the trial's own sample-size justification or a completed sample-size calculation. It also does not report an interim-analysis plan or interim results. These details should not be reconstructed from the trial's enrollment or endpoint description.

What can be concluded from the event counts?

The reason-for-discontinuation counts are descriptive. The record gives 13 (48%) removed due to progression, 11 (41%) secondary to toxicity, and 3 (11%) for other reasons. Those categories describe treatment status and recorded reasons; by themselves, they are not a survival analysis or a six-month endpoint estimate. A time-to-event analysis generally uses information about when events occur and how long participants are followed, while addressing participants whose event status is not observed by the analysis cutoff. The registry lists progression-free survival and median survival as secondary outcomes, but does not report their estimates or analytic details.

The serious and other adverse-event figures are also descriptive. Counts indicate how many participants in the group were recorded in each category, while event-term percentages describe the listed terms. Without a comparator, these data do not estimate a relative excess or reduction in risk. General statistical interpretation should distinguish the number of participants affected from the total number of event occurrences; the registry record does not provide a detailed event-counting convention for these figures.

Finally, the registry reports 0 analyses. This means the record does not include analysis entries; it does not prove that no analyses were ever conducted outside the registry. The analysis population, handling of incomplete observations, multiplicity strategy, and detailed statistical methods are not reported in the registry record. Those omissions limit independent evaluation of how the intended endpoint and secondary outcomes were analyzed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and secondary outcomes covering toxicity, PSA decline, progression-free survival, median survival, and objective response rate. It also reports six outcome measures in total. When a study examines multiple outcomes, the chance of at least one apparently notable result can increase if each is tested separately without accounting for multiplicity. In general, prespecified priorities and any adjustment strategy help readers distinguish confirmatory analyses from exploratory ones. A multiplicity adjustment plan or hierarchy is not reported in the registry record, so it is not possible to determine whether or how multiple outcome analyses were controlled.

The endpoint description says Fisher's Exact Test will be used, but no analysis result is posted. The registry record reports 0 analyses and does not provide an analysis population for the primary or secondary outcomes. The analysis population can affect a result because it defines which participants contribute to the estimate and how departures from treatment or missing assessments are handled.

Missing-data handling is especially relevant to the primary endpoint because all eligible patients were off therapy before the 6-month time point. The registry lists progression, toxicity, and other reasons for stopping treatment, but does not report a rule for assigning six-month progression status to participants without an assessment at that time. In general, treating an unobserved outcome as progression, excluding it, or using other follow-up information can lead to different estimates. No such method should be assumed.

Interim analyses, endpoint assessment procedures, and the primary analysis population are not reported in the registry record. The stated reason categories therefore provide useful context about treatment discontinuation, but they do not resolve how missing six-month outcome data were addressed.

11. 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: thrombosis (6.9%), abdominal pain (3.4%), arrhythmia (3.4%), back pain (3.4%), creatinine increased (3.4%).

The registry reports serious adverse events for the treatment group and lists 29 participants at risk, with 8 affected. It separately reports other adverse events, with 29 participants at risk and 29 affected. These figures refer to distinct reporting categories; they should not be added together or interpreted as a single count of unique participants with any event.

The most common serious event terms listed are Thrombosis (6.9%), Abdominal Pain (3.4%), Arrhythmia (3.4%), Back Pain (3.4%), Creatinine Increased (3.4%), and Dehydration (3.4%). These percentages are registry descriptions of the listed terms. The record does not provide a control group, so the figures do not indicate how event frequency compares with another treatment or with no treatment.

Adverse-event counts describe events recorded during the study, but do not alone establish that treatment caused them. The record does not report deaths; this should be read as deaths not reported in the registry record, not as evidence that none occurred. Details about event timing, duration, management, and individual participant overlap are also not reported in the registry record.

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

The information supports a descriptive reading of a phase II study in which 29 participants received vorinostat in a single treatment group. The primary question concerned the proportion without disease progression at 6 months. The registry states that all eligible patients were off therapy before this time point, and gives reasons for leaving treatment: 13 (48%) for progression, 11 (41%) secondary to toxicity, and 3 (11%) for other reasons.

Those discontinuation figures are not a reported six-month progression-free estimate. They also do not provide a treatment comparison. The record does not report a numerical primary endpoint result, confidence interval, or p-value. Although the endpoint description mentions Fisher's Exact Test, a result and the comparison needed to interpret it are not reported in the registry record.

The adverse-event figures describe events recorded in the treatment group. They can convey that serious adverse events affected 8 of 29 participants and that other adverse events affected 29 of 29, along with the listed serious event terms. They cannot establish comparative safety or causal attribution in this single-group design.

More broadly, an observed outcome in a treated group is not equivalent to evidence of what would have occurred under a different treatment. That counterfactual comparison requires a suitable design or assumptions that are not established by the registry information. The record also does not report detailed methods for missing endpoint data, multiplicity, or analysis populations. Accordingly, the posted information is insufficient to quantify the primary endpoint or draw a comparative treatment-effect conclusion. Unreported results should not be inferred from the study's objectives or planned methods.

13. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation begins with the design and the endpoint, not just the treatment name or the list of outcomes. A single-group phase II study can document participant experiences and outcomes during treatment. It does not contain a randomized comparator, so its results cannot directly estimate how outcomes would differ under another treatment.

The primary endpoint also highlights the difference between a planned measurement and an observed result. The stated question concerns progression at 6 months, but the record says all eligible patients were off therapy before that point. It reports reasons for leaving treatment, yet does not report the six-month endpoint estimate or explain how participants without an assessment at that time were classified. This makes the distinction between stopping treatment and an endpoint event particularly important.

The record further demonstrates why statistical methods need enough detail to be interpretable. Naming Fisher's Exact Test does not provide a result; readers also need the comparison, analysis population, outcome counts, and uncertainty information. Similarly, adverse-event counts describe the treated cohort but cannot establish comparative risks without a suitable reference group.

For clinical researchers and biostatisticians, the main statistical lesson is to separate what the registry directly reports from what the design could in principle estimate. Here, the posted details support a description of treatment discontinuation and safety counts. They do not report an estimate for the primary six-month question, and they do not establish comparative treatment effects. Clear reporting of endpoint ascertainment, missing-data rules, analysis populations, and results would be needed for a more complete statistical assessment.

14. 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 consequential limitation for interpreting the primary objective is that the record says all eligible patients were off therapy before the 6-month assessment time. Although the reasons for stopping are listed, the registry does not explain how progression status at 6 months was established for participants who were no longer receiving treatment. A six-month endpoint estimate and its uncertainty are not reported.

The single-group design has no randomized control arm. It can describe outcomes in the vorinostat group, but cannot directly distinguish treatment-associated changes from the natural course of disease or other influences. Masking is recorded as none, and the registry does not report procedures for blinded outcome assessment.

Several details needed for an independent analysis are not reported in the registry record: full eligibility criteria, baseline participant characteristics, progression definitions and assessment procedures, analysis populations, missing-data methods, multiplicity handling, sample-size justification, and interim-analysis details. The primary endpoint description mentions Fisher's Exact Test without reporting its comparison or result.

The record lists adverse-event counts and selected serious event terms, but does not provide a comparator, event timing, or detailed attribution information. Deaths and numerical results for the listed secondary outcomes are not reported in the registry record. These limitations mean the posted information is best read as a partial descriptive account, not as a complete analysis of efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vorinostat in Treating Patients With Progressive Metastatic Prostate Cancer — NCT00330161.
• Registry record last updated 2014-05-26; status last verified 2012-12.
• Results first posted 2014-05-26.
• 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.

18. Record Summary

NCT00330161 is a completed phase II, single-group trial sponsored by the National Cancer Institute (NCI), with enrollment of 29. It studied vorinostat in advanced prostate cancer after one prior chemotherapy, with no masking and no randomized allocation. The registry lists a start date of 2006-03 and primary completion of 2009-09.

The primary endpoint concerned the proportion without disease progression at 6 months. The record states that all eligible patients were off therapy before that time and lists discontinuation due to progression, toxicity, and other reasons. It does not report a primary endpoint estimate or analysis result. Serious adverse events affected 8 of 29 participants; other adverse events affected 29 of 29. The registry record does not report deaths or numerical findings for the listed secondary outcomes.