A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer (NCT00108732), a na phase 2 study. The primary outcome is Proportion of Patients Free of PSA Progression at 6 Months (Prior to the Start of Androgen Ablation).

2. Clinical Question

3. Trial Design

This completed Phase II study evaluated PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM with GM-CSF in patients with PSA progression after local therapy for prostate cancer. The National Cancer Institute sponsored the study. The registry records enrollment of 50 and a single-group model. Allocation is listed as not applicable, and masking as none; the record therefore describes neither a randomized comparison nor blinded treatment assignment.

Patients received vaccinia-PSA-TRICOM vaccine subcutaneously on day 1 and sargramostim, or GM-CSF, subcutaneously on days 1-4 during weeks 1-4. Beginning in week 5, the described regimen switched to fowlpox-PSA-TRICOM vaccine on day 1 and GM-CSF on days 1-4. The registry also lists bicalutamide and goserelin acetate. The primary endpoint was assessed before the start of androgen ablation, and the record says androgen ablation could be used when needed. The available regimen description ends before its full course is specified, so its complete duration is not reported in the registry record.

The study started in 2006-02, reached primary completion in 2010-10, and is recorded as completed. The primary analysis population was eligible and treated patients in step I; the registry does not report the size of that population. The design can describe outcomes among the analyzed patients, but without a concurrent control group it cannot estimate a treatment contrast against another assigned strategy. The registry record does not report a statistical analysis plan, sample-size justification, or interim-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.

Step 1 (Vaccinia/Fowlpox/GM-CSF)

Reasons for not completing this period:

Step 2 (Androgen Ablation and Vaccine)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only eligible and treated patients in step I are included in this analysis.

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 Proportion of Patients Free of PSA Progression at 6 Months (Prior to the Start of Androgen Ablation), measured over Assessed at 6 months.

The primary endpoint is the proportion of eligible and treated step I patients free of PSA progression at six months, assessed before androgen ablation. PSA is a laboratory marker used in prostate cancer monitoring. Tracking whether PSA meets a prespecified progression rule over a stated period provides a way to characterize disease course in this study population. The endpoint is not itself a measure of overall survival, symptoms, or tumor size.

The progression definition depends on the PSA pattern after treatment began. For patients whose PSA declined by more than 50%, progression required a rise of 50% over the nadir, confirmed by a second PSA two weeks later, with the rise at least 5 ng/mL or back to pretreatment baseline, whichever was greater. PSA changes below 5 ng/mL were not assessable for progression. For patients whose PSA did not decline by 50%, progression required a rise greater than 50% of baseline on trial or nadir PSA, whichever was lower, confirmed by a repeat PSA two weeks later; the PSA had to rise by at least 5 ng/mL.

These criteria make the endpoint a classification based on serial PSA measurements and defined thresholds. The registry record does not report how many patients met the free-of-progression endpoint, nor the corresponding 90% confidence interval. The definition and timeframe are reported, but the endpoint result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame what this study can and cannot show. The registry record identifies a proportion endpoint, a 90% confidence interval, a single-group design, and planning assumptions for a sample-size illustration. It does not report the primary numerical estimate, its interval limits, or a detailed statistical analysis plan. The methods below explain the meaning of these design features generally without inferring unreported analyses.

What does a proportion estimate describe?

A proportion expresses how many people in a defined analysis population meet a specified condition. Here, the condition is being free of PSA progression at six months under the registry's endpoint rules. The denominator is important: the registry states that only eligible and treated patients in step I were included, but the size of that analysis population is not reported. Enrollment is recorded as 50, but enrollment should not be substituted for the endpoint denominator unless the record establishes that they are the same population.

A proportion is descriptive of the patients included in its calculation. It does not, on its own, establish why the outcome occurred. In a single-group study, there is no randomized control outcome against which to compare the observed proportion. A comparison with an assumed or historical value would require a specified reference and a suitable analysis; no such comparison is reported in the registry record.

What does a confidence interval convey?

A confidence interval communicates statistical uncertainty around an estimate. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry identifies a 90% confidence interval for the primary endpoint, but does not report the interval bounds or the method used to construct it. It is therefore not possible to assess the width of the interval, the range of values compatible with the reported analysis, or whether the estimate is precise enough for any particular interpretation.

A confidence interval is not a guarantee that the true value lies within its limits, nor does an interval by itself resolve bias or limitations in study design. It quantifies uncertainty under the assumptions of the statistical procedure. Those assumptions and the interval calculation method are not reported in the registry record.

Why do the progression rules matter?

The primary endpoint uses different progression criteria depending on whether PSA declined by more than 50%. That distinction means endpoint classification depends on the observed PSA course, not just on a single measurement at six months. Confirmation by a second measurement is part of the stated definition, and the rise must meet additional magnitude criteria. The rules also exclude changes below 5 ng/mL from being assessable for progression. In general, such thresholds can reduce the influence of small PSA fluctuations on endpoint classification, while making the operational definition central to interpretation.

Because classification relies on repeated measurements, missing or mistimed PSA values could affect whether progression can be assessed. The record does not explain how such cases were handled, whether a missing confirmation measurement counted as progression, or whether any imputation was used. These details are important for reproducing and evaluating the endpoint analysis.

What can planning assumptions tell readers?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not features of the actual single-group treatment assignment. In particular, equal allocation between two arms in an illustration does not mean that this trial randomized patients between two arms.

A planning calculation estimates the sample size that would be needed under its stated assumptions; it does not report the study's observed outcome. If the effect used for planning comes from observed data, the resulting illustration is conditional on that effect and the chosen assumptions. It is not observed power and does not establish that the trial was designed with those assumptions. The registry record does not report the trial's own sample-size justification or the numerical planning estimates. General sample-size calculations can also be sensitive to the assumed effect and the statistical model, so their assumptions need to be read alongside any estimate.

The record notes that time-to-event planning tables use a total number of events, while other planning tables use participants per arm. That distinction is general to those planning calculations and does not change the single-group description of this trial. No time-to-event primary endpoint is identified in the record; the primary endpoint described is a six-month proportion.

Why does over-dispersion matter in general?

For count or binary outcomes, a statistical model may assume a particular amount of variation. Over-dispersion means the observed variation is greater than the model expects. If it is ignored, uncertainty can be understated, making confidence intervals too narrow or significance assessments too optimistic. This is a general consideration rather than a reported feature of this study: the registry record does not state that an over-dispersion adjustment was used or was needed.

Overall, the available methodological information supports a clear description of the endpoint, population restriction, confidence-interval level, and planning assumptions. It does not supply enough detail to reproduce the primary analysis or evaluate the reported precision, because the result, interval limits, analysis denominator, and key handling rules are not reported.

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("Vaccinia/Fowlpox/GM-CSF")
n      <- c(40)
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  Vaccinia/Fowlpox/GM-CSF  40  0  0.0  0.0  8.8  0.0  8.8  0.1  8.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and four analyses. The primary outcome is the proportion free of PSA progression at six months before androgen ablation. The secondary outcomes are the proportion with a PSA response, the difference between day 4 and day 15 PSA, and the difference between PSA slopes before and after treatment. The record does not explain whether each listed analysis corresponds to one outcome measure, whether additional analyses were performed, or how the analyses were prioritized beyond identifying the primary endpoint.

When several outcomes or analyses are considered, the chance of a chance finding can increase if results are interpreted without accounting for multiplicity. The registry record does not report whether any multiplicity adjustment was planned or applied, nor does it describe a hierarchy or decision rule for interpreting secondary outcomes. Without that information and the numerical results, the secondary outcomes cannot be assessed as a coordinated set of confirmatory tests.

The primary analysis population is specified as eligible and treated patients in step I. The record does not report the number included, the number with an evaluable PSA endpoint, or whether an intention-to-treat population was used for any analysis. It also does not report how missing PSA measurements, incomplete follow-up, withdrawal, or other unavailable outcomes were handled. No imputation method or sensitivity analysis for missing data is described in the registry record.

These omissions matter because eligibility, treatment receipt, endpoint evaluability, and missingness can affect the denominator and the interpretation of a proportion. The endpoint's reliance on serial PSA values and confirmation makes the handling of incomplete measurements especially relevant. The registry record provides the population definition and endpoint rules, but not enough information to reconstruct the analysis population or determine how missing observations influenced the result.

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: fever w/o neutropenia (2.0%), joint effusion (2.0%), muscle pain (2.0%).

The safety record lists a Vaccinia/Fowlpox/GM-CSF group with 50 at risk. It records 2 serious adverse-event affected and 44 other adverse-event affected. These are separate registry entries, and the record does not explain whether a person could be represented in both categories or how events were counted. They should not be added together to infer a count of people with any adverse event.

The listed serious-event terms are Fever w/o neutropenia, Joint effusion, and Muscle pain, each shown with a value of 2.0%. These are reported terms, not a complete description of event severity, duration, relatedness, or clinical course. The record does not report deaths in this group. The group-level entries do not supply a comparator, so they cannot establish how safety outcomes differ from another treatment or from no treatment.

In general, adverse-event counts describe observations recorded during a study and depend on how events were collected and classified. The registry record does not provide further detail on collection procedures or attribution. These figures should therefore be read as the safety entries recorded for this study, not as a comparative estimate of risk.

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

The registry record describes a Phase II, single-group study of vaccine therapy with GM-CSF in patients with PSA progression after local therapy for prostate cancer. Its primary question concerns the proportion of eligible and treated step I patients free of PSA progression at six months before androgen ablation. The endpoint has explicit PSA thresholds and confirmation requirements, and the record identifies a 90% confidence interval as its dispersion measure.

Those details establish what the study set out to measure, but the registry record does not report the observed primary proportion or the confidence interval. It is therefore not possible to state the study's primary result or how precisely it was estimated. The endpoint definition alone does not show how many patients remained free of PSA progression.

Even if a primary estimate were available, the single-group design would limit causal interpretation. An outcome observed during the study would describe the analyzed population under the study regimen; without a concurrent randomized comparator, it would not establish the difference attributable to the regimen. The study also does not establish outcomes beyond the measures and follow-up described in the registry record.

The listed secondary outcomes concern PSA response and PSA changes over time. Their numerical results are not reported in the registry record. Safety entries include serious and other adverse-event counts and listed serious-event terms, but do not provide a comparative assessment. The record also does not report the handling of missing endpoint data, details of the statistical analysis plan, or the number included in the primary analysis.

Accordingly, the most defensible interpretation is bounded: the registry defines a PSA-based six-month endpoint and describes a single-group treatment regimen, but it does not provide the primary numerical outcome needed to characterize the observed result. The design and missing reporting details also prevent a comparative treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly specified endpoint and an unavailable endpoint result. The registry describes a six-month PSA-progression definition in detail, including different rules according to the degree of PSA decline, confirmation by repeat measurement, and thresholds for an assessable rise. Such operational detail helps clarify what would count as progression in an analysis. It does not replace the estimate, denominator, or interval needed to judge the observed outcome.

The single-group structure is also central to interpretation. The study can describe outcomes among patients who met the stated analysis criteria, but it does not provide a randomized treatment contrast. That boundary is especially important when reading a study that evaluates a treatment regimen and follows a biomarker over time: a change during follow-up is not automatically evidence that the regimen caused the change.

The record further illustrates why analysis population and missing-data reporting matter for proportion endpoints. The primary analysis was limited to eligible and treated patients in step I, while the size of that group and the treatment of unavailable PSA assessments are not reported. Without those details, readers cannot fully assess the denominator or reproduce the analysis.

Finally, planning assumptions should not be confused with the actual study design or with observed power. The record's planning illustration uses assumptions that include equal allocation between two arms, even though the trial itself is listed as single-group. Recognizing this distinction helps prevent hypothetical planning calculations from being read as evidence of a randomized comparison or as a report of the trial's achieved statistical power.

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 principal limitation for statistical interpretation is that the registry record does not report the primary outcome estimate or its 90% confidence interval. It also does not report the number of eligible and treated step I patients included in that analysis. As a result, neither the observed proportion nor its precision can be evaluated from the record.

The single-group design has no randomized comparator, so it cannot establish a comparative treatment effect. Masking is listed as none, and the record does not describe a blinded outcome assessment. The primary outcome depends on serial PSA values and confirmation rules; the registry does not report how missing or incomplete PSA measurements were handled, or whether sensitivity analyses were performed.

The statistical analysis plan, sample-size justification, and interim-analysis plan are not reported in the registry record. Nor does it explain whether or how multiplicity was addressed across the primary and secondary outcomes. Numerical results for the listed secondary outcomes are not reported. These gaps limit assessment of the analyses beyond the primary endpoint's stated definition.

The described treatment regimen includes vaccine and GM-CSF, with bicalutamide and goserelin acetate listed and androgen ablation used when needed. The primary endpoint is assessed before androgen ablation, but the record does not provide the full treatment-course description or further detail about how subsequent androgen ablation related to later assessments. The safety entries lack a comparator and do not report deaths in the listed group. Taken together, the registry supports a description of the study design and endpoint rules, but limited evaluation of efficacy, precision, missingness, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Study of PROSTVAC-V (Vaccinia)/TRICOM and PROSTVAC-F (Fowlpox)/TRICOM With GM-CSF in Patients With PSA Progression After Local Therapy for Prostate Cancer — NCT00108732.
• Registry record last updated 2015-06-30; status last verified 2013-12.
• Results first posted 2013-04-04.
• 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

NCT00108732 is a completed Phase II, single-group study sponsored by the National Cancer Institute. It enrolled 50 and studied PROSTVAC-V and PROSTVAC-F vaccines with GM-CSF in patients with PSA progression after local therapy for prostate cancer. The study started in 2006-02 and reached primary completion in 2010-10. Allocation is listed as not applicable, and masking as none.

The primary outcome was the proportion of eligible and treated step I patients free of PSA progression at six months before androgen ablation, with a 90% confidence interval specified. The registry record describes the PSA progression criteria but does not report the primary estimate or interval. It also does not report the primary analysis denominator or missing-data handling. Safety entries list 50 at risk, 2 serious adverse-event affected, and 44 other adverse-event affected in the Vaccinia/Fowlpox/GM-CSF group. The available record supports description of the design and endpoint, but not a numerical assessment of the primary result or a comparative treatment-effect conclusion.