This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer (NCT01560923), a randomized phase 2 study. The primary outcome is Immune Response to Sipuleucel-T.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01560923 |
| Phase | Phase 2 |
| Condition | Metastatic Prostate Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 47 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Masonic Cancer Center, University of Minnesota |
| Results posted | Yes |
2. Clinical Question
Population
Men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The registry lists metastatic prostate cancer as the condition and records enrollment of 47.
Intervention
Oral indoximod twice daily for 6 months, beginning after the final sipuleucel-T infusion. The arm description specifies a dose of 1200 mg.
Comparator
An identical-looking placebo, given in the same manner, after sipuleucel-T. Both groups received sipuleucel-T as part of the study regimen.
Primary question
At 14 weeks from first leukapheresis, what immune response to sipuleucel-T was measured in each arm, using the frequency of antigen-specific, cytokine-producing cells responding to PA2024?
The registry describes a randomized, double-blind, parallel-group phase II study. Its primary endpoint concerns an immune assay, rather than a direct measure of tumor progression or survival. The central comparison is therefore whether the posted immune-response measurements differ between the indoximod and placebo arms at the stated assessment time.
The listed secondary outcomes include progression-free survival at 6 months, objective response rate, overall survival, quality-of-life scale results, and the ratio of antibodies to PA2024. Numerical posted results are available for progression-free survival at 6 months and overall survival. The registry record does not report numerical results for the other listed secondary outcomes.
3. Trial Design
This was a randomized, double-blind, parallel-group phase II study sponsored by Masonic Cancer Center, University of Minnesota. The registry lists the study as completed and records enrollment of 47. The study began on 2012-10-01, and primary completion is recorded as 2018-12-12.
Participants were assigned to sipuleucel-T followed by oral indoximod or to sipuleucel-T followed by placebo. The indoximod description specifies twice-daily oral administration at 1200 mg for 6 months, starting after the third and final sipuleucel-T infusion. Placebo was described as identical-looking and provided in the same manner. Double masking means the study was recorded as masked for participants and study personnel, but the registry record does not specify the masking roles or operational details.
The primary endpoint was immune response to sipuleucel-T, assessed 14 weeks from first leukapheresis. The description specifies an ELISPOT assay using whole PBMC to assess interferon gamma production in response to PA2024. The reported measure is a geometric mean in spots per ml with a 95% confidence interval.
The registry lists 6 outcome measures and 5 posted secondary outcomes. It does not report any analyses in the analysis count, and the posted analysis details for the secondary endpoints are absent. The registry record does not report a sample-size justification, the randomization procedure, allocation concealment details, or a prespecified statistical analysis plan. Those aspects should not be inferred from the phase, masking, or allocation labels.
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.
Before assignment: One patient withdrew or refused to participate after receiving protocol therapy
Overall Study
| Stage | Sipuleucel-T + Placebo | Sipuleucel-T + Oral Indoximod |
|---|---|---|
| STARTED | 24 | 22 |
| COMPLETED | 24 | 22 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Control (Placebo) Arm | Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 24 | 22 | 46 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 9 | 15 |
| Age, Categorical: >=65 years | Participants | 18 | 13 | 31 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 24 | 22 | 46 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 22 | 22 | 44 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 2 | 3 |
| Race (NIH/OMB): Asian | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 23 | 16 | 39 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Immune Response to Sipuleucel-T, measured over 14 Weeks from First Leukapheresis.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Spots per ml |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the immune response to sipuleucel-T measured at 14 weeks from first leukapheresis. The assay description identifies antigen-specific, cytokine-producing cells and focuses on interferon gamma production by whole PBMC in response to PA2024. Results are expressed as spots per ml and summarized as a geometric mean with a 95% confidence interval.
In general, an immune assay can provide a biological measure of whether an intervention is associated with a change in a targeted immune response. It is distinct from clinical outcomes such as progression, survival, symptoms, or quality of life. The endpoint is therefore useful for addressing the trial's stated immune-response question, but it does not by itself establish how the treatment groups compare on those other outcomes.
The posted geometric mean is 29.6 for the placebo arm, with a 95% confidence interval from 4.86 to 180.4. For the indoximod arm, the posted geometric mean is 25.45, with a 95% confidence interval from 2.92 to 222.1. These are arm-specific summaries; the registry record does not report a direct statistical comparison for this primary endpoint. The overlapping and broad intervals indicate substantial uncertainty in the arm-specific estimates, but they do not substitute for a comparative analysis.
The endpoint description explains how the assay was intended to measure the immune response. The registry record does not report assay validation details, the handling of measurements below assay limits, or the analysis population used for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results are geometric means of 29.6 spots per ml in the sipuleucel-T plus placebo arm and 25.45 spots per ml in the sipuleucel-T plus oral indoximod arm. The 95% confidence intervals are 4.86 to 180.4 and 2.92 to 222.1, respectively. These intervals are wide, so the arm-specific estimates are imprecise. The registry record does not report a comparative effect estimate, confidence interval for the difference, or p-value for the primary endpoint. A definitive statistical comparison of the primary outcome cannot be read from the arm summaries alone.
For progression-free survival at 6 months, the posted counts are 6 participants in the placebo arm and 11 in the indoximod arm. The unadjusted risk difference is 0.25, with a confidence interval from -0.021 to 0.521, and the unadjusted p-value is 0.079. The interval includes no difference and also permits a range of potentially meaningful differences in either direction. The p-value is an unadjusted result, not evidence that accounts for multiple secondary outcomes.
For overall survival at 2 years, the posted counts are 18 participants in the placebo arm and 17 in the indoximod arm. The unadjusted risk difference is 0.023, with a confidence interval from -0.224 to 0.269; the unadjusted p-value is 0.857. The interval is compatible with differences in either direction. These posted counts and summaries should be interpreted as registry results, not as evidence of a causal treatment effect.
The planning illustrations use the observed secondary endpoint effects to show hypothetical participants per arm for selected power targets. They are not observed power, do not explain the original trial's design, and should not be treated as a sample-size justification. For progression-free survival, the illustration gives 58 participants per arm for 80% power and 77 for 90% power when planning for 100% of the observed effect; for 75% of the observed effect, it gives 100 and 133; for 50%, 215 and 287. For overall survival, the corresponding figures are 5,521 and 7,390; 9,895 and 13,247; and 22,443 and 30,044. These are planning outputs under the stated assumptions, not additional findings from the trial.
9. Statistical Methods Explained
The primary outcome is reported as a geometric mean with a 95% confidence interval. A geometric mean is a way to summarize measurements that are positive and may vary over a broad range; it is based on multiplicative rather than additive averaging. This can make it a suitable summary for some biological measurements, but the registry record does not explain why this summary was selected or report the distribution of individual assay values.
In general, a confidence interval describes uncertainty around an estimate under the statistical procedure used to calculate it. A broad interval signals that the estimate is not very precise. The intervals for the two primary arm summaries are broad, and they overlap. Because they are separate arm-specific intervals, their overlap is not a formal test of the difference between arms. The registry record does not report a confidence interval or hypothesis test for the primary between-arm contrast.
The secondary progression-free survival and overall survival outcomes are presented as counts of participants, with unadjusted risk differences and confidence intervals. A risk difference expresses the difference between the observed proportions in the groups; it is an absolute, rather than relative, comparison. The reported risk-difference intervals include zero for both outcomes. In general, when a confidence interval for a difference includes zero, the data are compatible with no difference as well as with values on either side of zero. The interval's width also matters: a wide interval indicates considerable uncertainty about the size and direction of the contrast.
The reported p-values for these secondary comparisons are unadjusted. A p-value assesses how compatible the data are with a specified null model under the assumptions of the test; it does not give the probability that a treatment effect is true, nor does it measure the clinical importance of an effect. The registry record does not report adjusted p-values or a multiplicity procedure for the listed outcomes. Accordingly, the secondary p-values should be read as exploratory evidence rather than as confirmatory tests.
The registry also posts risk ratios and odds ratios for the secondary binary outcomes. These are relative measures, while the risk difference is an absolute measure. Relative measures can look different from absolute measures because they use different scales. For progression-free survival, the posted risk ratio is 2.0, with a confidence interval from 0.890 to 4.492, and the odds ratio is 3.0, with a confidence interval from 0.863 to 10.43. For overall survival, the risk ratio is 1.03, with a confidence interval from 0.746 to 1.424, and the odds ratio is 1.133, with a confidence interval from 0.291 to 4.413. These intervals are broad and include the null value for their respective relative measures. The registry record does not describe these as the sponsor's prespecified primary analyses.
The planning illustrations are explicitly based on observed effects and use a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The listed effect fractions refer to planning for 100%, 75%, or 50% of the observed effect. In general, sample-size planning asks how many participants would be needed under stated assumptions to detect an effect at a chosen power level. Smaller assumed effects generally require larger planned samples, all else equal. These calculations are illustrations only: they are not observed power, and the registry record does not report that these assumptions were used to design this trial.
For binary outcomes, planning values are stated as participants per arm. A planning estimate depends on the assumed event proportions, effect size, significance level, power target, and allocation. If the observed effect is unstable, planning from it can also be unstable. The posted planning numbers should therefore be treated as scenarios, not as a forecast of what a future study will achieve or as evidence about the reliability of the observed result.
In general, over-dispersion occurs when observations vary more than a statistical model assumes. It can make standard errors too small if the model fails to allow for that extra variability. The registry record does not report whether over-dispersion was assessed or relevant to the primary assay analysis, so no conclusion about its role in these results is possible.
The record does not report the statistical model, test, transformation, covariate adjustment, or confidence-interval method used for the primary endpoint. It also does not report how missing outcome data were handled, which analysis populations were used, whether an interim analysis occurred, or a detailed plan for secondary analyses. These omissions limit the ability to reproduce or fully assess the analyses from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary immune-response endpoint and multiple secondary outcomes, but it does not report a statistical plan describing how those outcomes were prioritized or how repeated testing was handled. A multiplicity procedure, when specified, can limit the chance of declaring a finding based on chance across a family of tests. Without a reported procedure or testing hierarchy, the posted secondary p-values should be treated as unadjusted and interpreted cautiously.
The registry record does not report the analysis population for the primary or secondary outcomes. It does not state whether analyses followed an intention-to-treat principle, were restricted to participants who received assigned treatment, or used another population definition. The record also does not describe exclusions, protocol deviations, or how participants with unavailable measurements were handled.
Missing-data methods are not reported in the registry record. This matters because estimates can be affected if outcome measurements are unavailable, especially when missingness differs between groups or is related to participant outcomes. The posted arm counts alone do not explain whether all assigned participants contributed to each outcome, or whether missing observations were excluded, imputed, or handled in another way.
The registry record does not report an interim-analysis plan, stopping rules, or a detailed analysis plan. It also does not report a primary-endpoint comparison statistic. These are not details that can be inferred from the randomized, double-blind design or from the posted endpoint summaries. Their absence restricts assessment of how prespecified the analyses were and how completely the reported results represent the planned analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sipuleucel-T + Indoximod | 2 | 22 | 9.1% |
| Sipuleucel-T + Placebo | 1 | 24 | 4.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sipuleucel-T + Indoximod | 5 of 22 |
| Sipuleucel-T + Placebo | 6 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sipuleucel-T + Indoximod | 20 of 22 |
| Sipuleucel-T + Placebo | 21 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | Sipuleucel-T + Indoximod | Sipuleucel-T + Placebo |
|---|---|---|---|
| Urinary tract obstruction | Renal and urinary disorders | 1 of 22 | 0 of 24 |
| Sepsis | Infections and infestations | 0 of 22 | 1 of 24 |
| Flank pain | Musculoskeletal and connective tissue disorders | 1 of 22 | 0 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sipuleucel-T + Indoximod | Sipuleucel-T + Placebo |
|---|---|---|---|
| Fatique | General disorders | 9 of 22 | 7 of 24 |
| Back pain | Musculoskeletal and connective tissue disorders | 6 of 22 | 7 of 24 |
| Constipation | Gastrointestinal disorders | 4 of 22 | 4 of 24 |
| Diarrhea | Gastrointestinal disorders | 2 of 22 | 6 of 24 |
| Headache | Nervous system disorders | 4 of 22 | 4 of 24 |
| Hot flashes | Vascular disorders | 3 of 22 | 5 of 24 |
| Nausea | Gastrointestinal disorders | 3 of 22 | 4 of 24 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 3 of 22 | 4 of 24 |
| Pain | General disorders | 1 of 22 | 5 of 24 |
| Fever | General disorders | 3 of 22 | 2 of 24 |
Serious events with the highest arm-level rate: urinary tract obstruction (4.5%), flank pain (4.5%), sepsis (4.2%).
The registry posts serious adverse event and other adverse event counts by arm. For serious adverse events, 2 of 22 participants are recorded as affected in the sipuleucel-T plus indoximod group, and 1 of 24 in the sipuleucel-T plus placebo group. For other adverse events, the corresponding affected counts are 20 of 22 and 21 of 24. The record separately lists 5 deaths in the indoximod group and 6 in the placebo group.
These counts describe events recorded in the registry; they do not establish that an event was caused by a study treatment. The registry lists urinary tract obstruction and flank pain at 4.5% each, and sepsis at 4.2%, among the top serious terms. It does not provide enough detail in the registry record to establish event timing, severity beyond the serious-event classification, attribution, recurrence, or the relationship of deaths to treatment.
In general, safety counts should be read alongside the population at risk, event definitions, follow-up duration, and event-level details. The registry record does not report a comparative statistical analysis of adverse events. The counts are descriptive and should not be interpreted as a formal estimate of a treatment-related difference.
12. What the Result Does, and Does Not, Mean
The registry records an immune-response endpoint measured by ELISPOT and posts separate geometric means for the placebo and indoximod arms. Those summaries describe the assay results, but the record does not include a direct comparison or inferential analysis for the primary endpoint. The arm-specific confidence intervals are broad, leaving substantial uncertainty around each estimate.
The available secondary results show counts and unadjusted comparisons for progression-free survival at 6 months and overall survival at 2 years. Their confidence intervals include no difference and allow a range of values in either direction. The results therefore do not identify a precise comparative effect. The unadjusted p-values do not account for the multiple secondary outcomes listed in the record.
These findings do not establish whether the regimens differ on the primary immune outcome or on the broader clinical outcomes. They also do not support a conclusion about treatment causation from the descriptive safety counts. The registry record does not report numerical results for several listed secondary outcomes, a primary comparison analysis, or the analysis details needed to fully evaluate missing data and populations.
In general, a registry result is best interpreted within the limits of its reported endpoints, estimates, uncertainty, and methods. The posted numbers are informative descriptions of what was recorded, but they do not resolve the unanswered statistical questions. They should not be treated as medical advice or as a substitute for a complete clinical and statistical assessment.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between a biological endpoint and outcomes that directly describe participants' clinical course. Its primary measure is an immune assay response to PA2024, while the listed secondary outcomes include progression-free survival, overall survival, response, quality of life, and antibody ratios. These outcome types answer different questions and should not be treated as interchangeable evidence.
The record also illustrates why arm-specific summaries are not enough for a treatment comparison. The primary geometric means and their confidence intervals describe each group, but no direct contrast is reported. The secondary risk differences offer comparisons, yet their intervals are broad and their p-values are unadjusted. Effect estimates, precision, and analysis context all matter; a p-value alone cannot convey the full strength or uncertainty of evidence.
Finally, the planning illustrations make clear that the sample size required in a future study depends on the effect size assumed. The listed scenarios are based on observed effects and specified planning assumptions, not on observed power or the original design justification. This is a reminder that small or imprecise results can yield unstable planning inputs, and that planning assumptions should be stated transparently.
The registry record is therefore statistically informative both for its posted estimates and for the gaps in reported methods. A clear account of the primary comparison, analysis populations, missing-data handling, and multiplicity would make the results easier to assess and reproduce.
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.
Several limitations are specific to the posted record. Although the primary outcome is clearly described as an immune assay measure at 14 weeks from first leukapheresis, no direct between-arm estimate or test is reported. The separate geometric means and confidence intervals do not establish the size or precision of a primary treatment contrast.
The secondary outcome reporting is incomplete: numerical results are available for progression-free survival and overall survival, while the record does not report numerical results for objective response rate, quality-of-life scale results, or the ratio of antibodies to PA2024. It also does not report analyses for these outcomes. As a result, the posted secondary results do not give a complete account of the outcome set listed in the registry.
The record does not report the statistical analysis plan, analysis populations, missing-data procedures, or the methods used to calculate the primary endpoint confidence intervals. It also does not report a multiplicity strategy. These omissions limit assessment of prespecification, robustness, and the potential influence of unavailable observations.
The planning illustrations rely on observed effects and stated assumptions, so they should not be treated as the trial's design rationale. The registry record does not report a sample-size justification. Finally, adverse-event counts are descriptive; without event-level attribution and a reported comparative safety analysis, they cannot establish treatment-related differences.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer — NCT01560923.
- Registry record last updated 2020-04-03; status last verified 2020-03.
- Results first posted 2020-04-03.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01560923 is a completed randomized, double-blind, parallel-group phase II study of sipuleucel-T followed by oral indoximod or placebo in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. The registry records enrollment of 47 and identifies immune response to sipuleucel-T at 14 weeks from first leukapheresis as the primary endpoint.
The primary results are arm-specific geometric means with 95% confidence intervals, without a reported comparative analysis. Numerical secondary results are posted for progression-free survival at 6 months and overall survival at 2 years, with unadjusted comparisons. The registry record does not report numerical findings for several other listed secondary outcomes or key analysis details, including missing-data handling, analysis populations, and multiplicity procedures.