Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer (NCT01804465), a randomized phase 2 study. The primary outcome is Percentage of Participants With an Immune Response to Prostatic Acid Phosphatase (PAP) and/or PA2024.

2. Clinical Question

3. Trial Design

This completed phase 2 study was a randomized, unmasked, parallel-group trial in prostate cancer. It enrolled 50 participants. Both arms received sipuleucel-T followed by ipilimumab; the planned contrast was the timing of the ipilimumab course after the final sipuleucel-T dose. In the immediate arm, ipilimumab began 1 day after that dose. In the delayed arm, it began 3 weeks afterward. Both schedules specified ipilimumab every 3 weeks for 4 doses.

The primary endpoint was the percentage of participants with an immune response to PAP and/or PA2024, assessed up to 20 weeks. The record reports an immune-response result for 7 participants in the immediate arm and 8 in the delayed arm. It also notes that only a small portion of collected samples contained enough aliquots or tissue for this analysis. These endpoint denominators are therefore smaller than the overall enrollment; the record does not explain why particular samples were unavailable or whether the analyzed participants differed from those without evaluable samples.

The registry lists 7 secondary outcomes, including PSA declines, objective and radiographic response measures, and time to PSA progression. The record does not report analyses for these secondary outcomes. It lists the study as completed, with a start date of 2014-04-22 and a primary completion date of 2020-02-27. Details such as the randomization method, allocation concealment, follow-up beyond the primary endpoint timeframe, and the planned analysis population are not reported in the registry record. The posted primary percentages can describe the analyzed samples, but the record does not provide enough information to assess how representative those samples are of all randomized participants.

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: Only a small portion of the collected samples contained enough aliquots or tissue available for this particular 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 Percentage of Participants With an Immune Response to Prostatic Acid Phosphatase (PAP) and/or PA2024, measured over Up to 20 weeks.

The primary endpoint measures the proportion of analyzed participants who had an antibody response to PAP and/or PA2024. The registry describes assessment of IgM and IgG antibodies by ELISA at baseline and week 20 after the start of sipuleucel-T, identified as day 113 of study treatment. A positive response is defined as a titer > 1:400. The record says the positive immune percentage for both IgG and IgM antibodies to PAP and to PA2024 is used to summarize results for each arm.

An immune-response endpoint is a laboratory measure: it records whether an antibody result meets the specified threshold. It is not itself a measure of symptoms, tumor shrinkage, survival, or time to disease progression. The trial also listed several clinical and PSA-related secondary outcomes, but their results are not reported in the registry record.

The registry identifies a single-sample binomial exact test for the immune response when induction therapy is completed. It reports 71.4% for 7 analyzed participants in the immediate arm and 87.5% for 8 in the delayed arm. The record does not report confidence intervals or a statistical test comparing the two arm percentages. The stated endpoint timeframe is up to 20 weeks, and the record notes that only a small portion of collected samples had enough material for this analysis. This limited sample availability is important when interpreting what the endpoint percentages represent.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a percentage and identifies a single-sample binomial exact test when induction therapy is completed. The posted arm results are proportions of analyzed participants meeting the antibody-response definition. The main statistical distinction is between describing each arm separately and testing whether the arms differ. The record reports the former, but does not report an inferential two-arm comparison.

What does a binomial exact test do?

In general, a binomial model represents an outcome with two categories, such as meeting or not meeting a prespecified response definition. A response percentage summarizes the observed share meeting that definition. A single-sample test compares one group’s observed response with a reference probability specified for the test. An exact test calculates probabilities under the binomial model without relying on a large-sample normal approximation. This can be useful when the analyzed group is small. The registry names this test but does not report its reference probability or test result, so neither can be reconstructed from the posted percentages.

The word “exact” describes how the test probability is calculated under its statistical assumptions; it does not mean that the estimated response percentage has no uncertainty. In general, a confidence interval gives a range of values compatible with the observed data under a stated method. The registry record does not report confidence intervals for the arm results. It also does not report the method used to calculate any interval, or a test that directly compares the immediate and delayed groups. A single-sample test in each arm, even if results were posted, would not by itself be the same as a direct test of the difference between arms.

Why do the denominators matter?

The primary percentages are based on 7 analyzed participants in the immediate arm and 8 in the delayed arm. The registry notes that only a small portion of collected samples had adequate aliquots or tissue for this analysis. These denominators describe the people included in the endpoint results, not the total enrollment. In general, fewer observations mean less information about the underlying response probability and greater sensitivity of a percentage to individual outcomes. No additional precision measure is posted, so the degree of uncertainty cannot be quantified from the registry record.

When a randomized trial has endpoint measurements missing for some participants, the analysis population and missing-data approach affect how its results should be interpreted. General approaches can include analyzing participants according to randomized assignment, analyzing only those with an evaluable endpoint, or using a specified model for missing outcomes. These are not interchangeable. The registry record does not report which population was used for the primary endpoint, how missing samples were handled, or whether sample availability was examined by arm. It therefore does not support an assessment of possible selection related to sample availability.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable at the start of a trial, on average, and to reduce confounding in a comparison of assigned strategies. Here the randomized contrast was immediate versus delayed ipilimumab after sipuleucel-T. Randomization does not ensure that every endpoint subset remains comparable if measurements are unavailable for many participants. Nor does the word “randomized” alone reveal how the sequence was generated, whether assignment was concealed, or whether the analysis followed assignment. Those procedural and analysis details are not reported in the registry record.

The trial was unmasked, meaning the registry lists no masking. Masking can be relevant to how participants, clinicians, or assessors behave or evaluate outcomes; the record does not specify which parties knew treatment timing or whether outcome assessment was masked. The primary endpoint is an antibody assay, but the registry does not give further information about laboratory blinding or assay quality control. These details should not be assumed.

How should sample-size illustrations be read?

General sample-size planning asks how many participants would be needed to detect a specified effect under stated assumptions. The registry-related planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with target effects expressed as fractions of the observed effect. Such figures are planning illustrations, not the trial’s observed power and not evidence that a planned effect was detected. The registry does not report the trial’s own sample-size justification. Because the two-arm binary endpoint comparison is not estimable in the posted results, no particular planning figure should be treated as a direct test of the trial’s primary contrast.

More generally, statistical significance and clinical importance are distinct concepts. A test addresses compatibility with a statistical null model under specified assumptions; it does not establish that a measured difference matters clinically. Conversely, a non-significant test would not prove that groups are identical. In this record, no direct two-arm test result or confidence interval is reported, so neither statistical significance nor the precision of the arm contrast can be evaluated. The posted values support a descriptive account of the analyzed samples, with substantial limits on broader inference.

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("Immediate IpilimumabTreatment", "Delayed IpilimumabTreatment")
n      <- c(7, 8)
events <- c(5, 7)
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  Immediate IpilimumabTreatment  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5
ARM  Delayed IpilimumabTreatment  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 secondary outcomes in addition to the primary immune-response endpoint. These include PSA declines of at least 30% and at least 50% below baseline, objective response, objective response stratified by prior radical prostatectomy and by radiation therapy, radiographic clinical response rate, and median time to PSA progression. Results for these secondary outcomes are not reported in the registry record. The record does not report a multiplicity procedure or a hierarchy governing interpretation across outcomes. In general, examining multiple outcomes can increase the chance of at least one apparently notable result by chance; prespecified adjustment or a testing hierarchy can address that issue. No such plan should be inferred for this trial.

The record identifies a single-sample binomial exact test for the primary immune response, but does not report the reference probability, test result, or a direct comparison between arms. It reports no analyses. There is consequently no posted inferential result from which to assess a multiplicity-adjusted claim.

Missing endpoint information is a central limitation. Only a small portion of the collected samples had enough aliquots or tissue for the primary analysis, which includes 7 participants in the immediate arm and 8 in the delayed arm. The registry record does not report the reasons samples could not be analyzed, how many participants lacked samples in each arm, or any method for handling missing endpoint data. It also does not report whether the analyzed population was defined before results were known.

The analysis populations for the secondary outcomes and the safety summaries are not described in detail. The record does not report an intention-to-treat analysis definition, per-protocol criteria, or sensitivity analyses for missing data. These gaps prevent assessment of whether the immune-response subset represents the randomized groups and how robust any comparison would be to alternative handling of unavailable measurements.

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: colitis (11.5%), diarrhea (11.5%), vascular disorders - other (4.2%), chills (4.2%), fever (4.2%).

The safety record reports serious adverse events for 24 participants at risk in the immediate arm and 26 at risk in the delayed arm. The serious-event counts are 1 and 11, respectively. Other adverse events are reported for 21 of 24 at risk in the immediate arm and 26 of 26 at risk in the delayed arm. Death counts are 0 in the immediate arm and 1 in the delayed arm. These are separate safety summaries; they should not be confused with the primary immune-response denominators of 7 and 8.

The registry also lists serious adverse-event terms with percentages: colitis and diarrhea at 11.5% each, vascular disorders - other and chills at 4.2% each, fever at 4.2%, and endocrine disorders - other at 3.8%. The record does not assign these listed terms to a specific treatment arm in the information, so they should not be attributed to either arm individually. Nor does the record provide event timing, duration, severity breakdown beyond the serious classification, or a safety follow-up timeframe.

These figures describe recorded safety events in this trial. They do not by themselves show that treatment timing caused an event or establish a comparative safety effect. Differences in the number at risk and the absence of further analysis details are relevant when reading the arm summaries.

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

The primary endpoint results report immune-response percentages of 71.4% for the immediate-treatment arm and 87.5% for the delayed-treatment arm. Those values describe the analyzed sample subsets: 7 participants and 8 participants, respectively. They are not estimates based on all 50 enrolled participants. The registry notes that only a small portion of collected samples contained enough aliquots or tissue for this analysis.

The record does not report a direct statistical comparison of the two percentages, confidence intervals, or the result of the named single-sample binomial exact test. As a result, the precision of the percentages and the uncertainty around an arm-to-arm contrast cannot be assessed from the registry. The values alone do not establish that the timing strategies differ, or that they are equivalent. Lack of a reported comparison is not evidence of no difference.

The endpoint is an antibody-based laboratory measure at a defined threshold. It is not a direct measure of a clinical outcome. The registry lists PSA, objective-response, radiographic-response, and PSA-progression outcomes, but their results are not reported in the registry record. The primary percentages therefore cannot stand in for those outcomes or answer questions about them.

The trial’s design addresses the timing of ipilimumab after sipuleucel-T, with both arms receiving both treatments. It does not compare sipuleucel-T with no sipuleucel-T or ipilimumab with no ipilimumab. The posted primary results also do not establish whether either schedule improves health outcomes. Any interpretation must remain specific to the endpoint, the small analyzed subset, and the missing inferential detail. The record supports reporting what was observed in the available samples, but not a broader claim about clinical effectiveness or comparative benefit.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a randomized design and the data available for a particular endpoint. Randomization can support a fair comparison of assigned strategies, but the primary immune-response analysis includes only 7 participants in one arm and 8 in the other. The registry says only a small portion of collected samples had sufficient aliquots or tissue. The endpoint results therefore need to be read in light of sample availability, not simply the overall enrollment of 50.

It also illustrates why descriptive percentages and comparative inference are different. The record posts an immune-response percentage for each arm, but does not report a direct statistical comparison, confidence intervals, or the result of the named exact test. Without those elements, readers cannot judge the precision of the percentages or how compatible the observed arm contrast is with chance variation under a specified model. A pair of percentages is not, by itself, a complete statistical comparison.

The trial also separates a laboratory endpoint from the clinical outcomes listed as secondary measures. An antibody response is a distinct outcome from PSA change, objective response, radiographic response, or time to PSA progression. The latter outcomes are not reported in the registry record, so the primary measure cannot answer those questions.

Finally, the record shows why transparent reporting of analysis populations, missing-data handling, and multiplicity plans matters. The registry does not describe these details. Their absence limits the conclusions readers can draw, even though the study is completed and its primary arm percentages are posted. Statistical interpretation depends not only on the numerical result, but also on who contributed data, how outcomes were analyzed, and how uncertainty was quantified.

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 immediate limitation is the size of the analyzed primary endpoint subsets: 7 participants in the immediate arm and 8 in the delayed arm. The registry states that only a small portion of collected samples had enough aliquots or tissue for this analysis. It does not explain the sample-availability process, identify reasons samples were unavailable, or describe whether the availability pattern differed by arm. This makes it difficult to assess how representative the analyzed participants are of the randomized groups.

Although the registry names a single-sample binomial exact test, it does not report the reference probability or test result. No direct two-arm test, confidence interval, or comparative estimate is reported for the primary endpoint. The precision of the arm percentages and the uncertainty around their contrast therefore cannot be assessed using the posted results. The record also does not report the analysis population or a missing-data strategy.

The trial is unmasked, and the registry does not provide further detail about who knew treatment assignment or whether laboratory outcome assessment was masked. It does not report the randomization procedure or allocation concealment. These are reporting gaps, not evidence that a particular procedure was or was not used.

The registry lists 7 secondary outcomes but does not report their results or a multiplicity plan. It also does not report the trial’s own sample-size justification, detailed analysis plan, or sensitivity analyses. Finally, the posted primary endpoint is an antibody measure; it does not substitute for the clinical outcomes also listed in the record. These limitations restrict interpretation to the descriptive immune-response results in the small analyzed subsets and the safety summaries reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sipuleucel-T With Immediate vs. Delayed Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Blockade for Prostate Cancer — NCT01804465.
• Registry record last updated 2021-08-18; status last verified 2021-07.
• Results first posted 2021-01-25.
• 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

NCT01804465 is a completed randomized phase 2, unmasked, parallel-group trial in prostate cancer, sponsored by the University of California, San Francisco. The registry enrollment is 50. Both arms received sipuleucel-T followed by ipilimumab every 3 weeks for 4 doses; the timing differed, with ipilimumab starting 1 day after the final sipuleucel-T dose in the immediate arm and 3 weeks afterward in the delayed arm.

The primary endpoint was the percentage of participants with an immune response to PAP and/or PA2024, assessed up to 20 weeks and defined using an antibody titer > 1:400. The posted percentages are 71.4% among 7 analyzed participants in the immediate arm and 87.5% among 8 in the delayed arm. The registry notes limited sample availability for this analysis and does not report a direct two-arm comparison or confidence intervals.

Seven secondary outcomes are listed, but their results are not reported in the registry record. Safety summaries list serious events, other adverse events, and deaths by arm. Important analysis details, including missing-data handling and the analysis populations, are not reported.