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 Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases (NCT02758132), a non-randomized phase 2 study. The primary outcome is Measure Change in Serum-based Metabolites Associated With Bone Deposition, Growth and Turnover in Patients Who Have CRPC With Clinical Evidence of Metastatic Disease to the Bone, All Using Gas Chromatography-time-of-flight Mass Spectrometry (GC-TOFMS)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02758132 |
| Phase | Phase 2 |
| Condition | Prostate Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Hawaii |
| Results posted | Yes |
2. Clinical Question
Population
Men with castrate resistant prostate cancer (CRPC) and bone metastases are named in the study title. The brief summary describes a correlative study of patients with newly diagnosed metastatic CRPC who were not currently receiving bone targeting agents. The registry record reports an enrollment of 1 and says the patient expired before completing the study.
Intervention
The arm labelled Alliance A031201 is described as denosumab plus enzalutamide, abiraterone and prednisone. The intervention list also names denosumab as a biological intervention and enzalutamide, abiraterone and prednisone as drugs.
Comparator
The arm labelled Standard of Care is described as denosumab plus enzalutamide alone. Allocation is listed as non-randomized, so the arms should not be treated as a like-for-like randomized control comparison.
Primary question
The primary outcome concerns change in serum metabolites associated with bone deposition, growth and turnover, measured using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). The registry record names measurement before registration, at registration, and on Day 1 of cycle 4 and 13. It does not report a metabolite result or a completed comparison between arms.
3. Trial Design
This is a phase 2, parallel, non-randomized study with no masking. It was sponsored by the University of Hawaii, and its listed condition is prostate cancer. The study began on 2016-03-01, had a primary completion date of 2016-09-06, and is marked terminated. The enrollment is 1.
The study title describes a comparison of denosumab plus enzalutamide, abiraterone and prednisone with denosumab plus enzalutamide alone. The arm descriptions use the labels Alliance A031201 and Standard of Care, respectively. Because allocation is non-randomized, differences between these groups would not have the protection against selection bias that random allocation is intended to provide. With enrollment of 1, the registry record does not support a meaningful comparison of outcomes between the arms.
The brief summary characterizes the study as correlative: its aim is to characterize serum metabolites associated with bone deposition, growth and turnover in patients with newly diagnosed metastatic CRPC who were not currently receiving bone targeting agents. The listed secondary outcomes concern time to a skeletal related event, progression-free survival and duration of response. The record reports 8 outcome measures, but does not give names or details for all of them.
The registry record does not report the protocol, eligibility criteria beyond the summary and title, reasons for termination, or the allocation process. It also does not report a sample-size justification or explain how the intended two-arm comparison was to be conducted.
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
| Stage | Alliance A031201 | Standard of Care |
|---|---|---|
| STARTED | 0 | 1 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Patient expired before completing study
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Patient expired before completing study
| Characteristic | Unit | Alliance A031201 | Standard of Care | Total |
|---|---|---|---|---|
| Participants analysed | 0 | 1 | 1 | |
| Age, Categorical: <=18 years | Participants | — | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | — | 0 | 0 |
| Age, Categorical: >=65 years | Participants | — | 1 | 1 |
| Sex: Female, Male: Female | Participants | — | 0 | 0 |
| Sex: Female, Male: Male | Participants | — | 1 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | — | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | — | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | — | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | — | 0 | 0 |
| Race (NIH/OMB): White | Participants | — | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | — | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | — | 1 | 1 |
| Region of Enrollment: United States | participants | — | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Measure Change in Serum-based Metabolites Associated With Bone Deposition, Growth and Turnover in Patients Who Have CRPC With Clinical Evidence of Metastatic Disease to the Bone, All Using Gas Chromatography-time-of-flight Mass Spectrometry (GC-TOFMS)., measured over Prior to Registration, Registration, Day 1 of cycle 4 and 13.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is a change in serum-based metabolites associated with bone deposition, growth and turnover in patients with CRPC and clinical evidence of metastatic disease to bone. The specified measurement method is gas chromatography-time-of-flight mass spectrometry (GC-TOFMS). The timeframe lists measurement prior to registration, at registration, and on Day 1 of cycle 4 and 13.
In general, a biomarker endpoint can describe biological features or changes that are relevant to a disease process. Repeated measurements can be useful for characterizing how measured markers vary over time. Such measurements require clear definitions of the metabolites, assay procedures, timing, and the approach to comparing observations. Those details, including the particular metabolites and the endpoint’s unit and summary parameter, are not reported in the registry record.
The record identifies the primary outcome population as a patient who expired before completing the study. It does not provide measurements, a change estimate, or an analysis of the endpoint. Therefore, the intended biomarker question is identifiable, but the posted record does not establish what the measurements showed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this was a terminated phase 2 study with non-randomized allocation, no masking, and enrollment of 1. It does not report a completed primary outcome analysis. No metabolite values, estimates of change, measures of uncertainty, or statistical test results are listed. Consequently, there is no posted estimate from which to judge the direction, size, or precision of a metabolite change.
The primary outcome description identifies a planned biomarker assessment over specified study timepoints, but the listed population says the patient expired before completing the study. The record does not clarify which measurements were obtained before that point. Without observations and a clear accounting of measurement availability, a within-person pattern or comparison across timepoints cannot be evaluated.
The two named arms also cannot be interpreted as a treatment comparison on the basis of this record. Allocation was non-randomized, and enrollment was 1. The registry record does not identify which arm included the enrollee. Even if an arm assignment were known, a single enrollee would not provide a basis for estimating comparative effects or separating treatment-related differences from individual variation and other influences.
The secondary outcomes are time to skeletal related event, time to progression-free survival, and duration of response. These are named outcomes, not reported findings: the record provides no event times, response estimates, or analyses for them. It reports no listed statistical analyses. The number of outcome measures is 8, but the record does not give complete details for all of them.
Serious adverse event information is also very limited. The Alliance A031201 group has zero participants at risk and zero serious events reported. The Standard of Care group has 1 participant at risk and 1 with a serious event; 1 death is also reported in that group. These counts do not establish a causal relationship between an intervention and an event. The registry record does not report event timing, attribution, or an explanation of the death.
Overall, the posted record describes the study’s question and design but does not provide an interpretable estimate of the primary outcome or a comparative treatment result. The absence of a reported estimate is not evidence that there was no change or no difference.
9. Statistical Methods Explained
The design features determine what kinds of conclusions a study can support. This study is listed as parallel, non-randomized and unmasked. In a parallel design, participants are assigned to one arm rather than switching between arms, but the registry record does not report how assignment was made. In general, randomization helps balance known and unknown prognostic factors across groups on average. Non-randomized allocation can leave groups different for reasons that also influence outcomes, so an observed contrast would not automatically represent a treatment effect. The record explicitly cautions that the arms are not a like-for-like control comparison.
What can the primary endpoint estimate?
The primary outcome concerns serum metabolites associated with bone deposition, growth and turnover, using GC-TOFMS, at the listed study timepoints. In general, a change endpoint requires a defined measurement at each relevant time and a prespecified way to summarize change. For example, an analysis might focus on within-person change, a difference between arms, or a model using all repeated measurements. These approaches answer different questions. The registry record does not report which estimand or statistical model was planned, nor the endpoint’s unit, parameter or dispersion measure. It reports no metabolite observations or calculated change.
In general, a confidence interval describes the range of effect values compatible with the data under the model and its assumptions. Its width reflects precision as well as the amount and variability of information. A point estimate without an uncertainty measure can conceal substantial imprecision. No estimate or confidence interval for the primary outcome is reported in the registry record, so precision cannot be assessed.
What does non-randomized allocation mean for interpretation?
In general, an unadjusted comparison summarizes what was observed in groups, but it does not address confounding. Adjustment can sometimes account for measured differences, though it cannot guarantee control of unmeasured differences. The registry record does not report an adjustment plan, covariates, or an analysis population. Given the enrollment of 1, it also does not provide data for a useful arm-level estimate. No analysis details are listed that would allow readers to assess assumptions or reproduce a comparison.
How should the planning illustrations be read?
The record describes sample-size calculations as planning illustrations based on an observed effect, not as the trial’s own design or as observed power. It states that the illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustrations use total event counts based on the Schoenfeld approach; other outcomes are expressed as participants per arm. These are planning conventions, not evidence that the study enrolled the indicated number or had a particular probability of detecting an effect. The record does not report a trial-specific sample-size justification. No numerical planning results are stated in the registry record.
In general, over-dispersion means that observed variability exceeds what a simple model assumes. If it is ignored, uncertainty can be understated and statistical tests may be poorly calibrated. The registry record does not report a count-data model or an over-dispersion assessment; this general issue cannot be connected to a posted analysis for this study.
What can the listed analyses establish?
The registry record lists no statistical analyses. It provides no test statistics, p-values, effect estimates, confidence intervals, or model specifications for the primary or secondary outcomes. General principles about statistical significance cannot substitute for those missing results. A p-value, when reported, describes compatibility between data and a specified null model; it does not measure effect size or establish causation. Here, there is no posted p-value to interpret.
The serious adverse event counts are descriptive registry entries, not a comparative safety analysis. A denominator, consistent follow-up, event definitions, attribution, and appropriate uncertainty assessment are important for comparing safety across groups. The record’s small and unequal group counts do not permit a stable comparative estimate. The event data should therefore be read as a limited account of what was registered, rather than as a quantified assessment of relative risk.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a primary metabolite outcome and secondary outcomes concerning time to skeletal related event, progression-free survival and duration of response. It reports 8 outcome measures overall, but does not provide complete descriptions for all of them. The registry record does not report a multiplicity plan, such as a hierarchy of hypotheses or an adjustment for testing multiple outcomes. In general, when many outcomes or analyses are examined, the chance of at least one apparently notable result can increase; a prespecified plan helps readers distinguish confirmatory questions from exploratory ones. No outcome-specific analysis results are available to evaluate in this case.
The registry record identifies the primary outcome population as a patient who expired before completing the study, but does not state which endpoint measurements were available, when they were collected, or how incomplete follow-up was handled. It does not report a missing-data strategy, imputation method, sensitivity analysis, or reasons for missing measurements. In general, missing-data methods rely on assumptions about why observations are missing. Those assumptions cannot be assessed without a record of what was missing and why.
The record does not report an analysis population definition, such as whether analyses were intended to include all registered participants or only those with specified measurements. It also does not explain handling of protocol deviations or treatment exposure. These omissions limit interpretation of any potential analysis, and no completed analysis is listed. No missingness mechanism or multiplicity method should be inferred from the registry entry.
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 |
|---|---|---|---|
| Standard of Care | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Alliance A031201 | 0 of 0 |
| Standard of Care | 1 of 1 |
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 |
|---|---|
| Alliance A031201 | 0 of 0 |
| Standard of Care | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Alliance A031201 | Standard of Care |
|---|---|---|---|
| intracranial hemorrhage | Nervous system disorders | 0 of 0 | 1 of 1 |
Serious events with the highest arm-level rate: intracranial hemorrhage (100.0%).
The serious adverse event entries are small descriptive counts. For Alliance A031201, the registry lists zero participants at risk and zero participants affected by a serious event. With no participants at risk recorded for that group, these zeros should not be read as evidence that the group had no serious-event risk.
For Standard of Care, the registry lists 1 participant at risk, 1 affected by a serious event, and 1 death. It also lists zero participants affected by other adverse events. The serious term reported is intracranial hemorrhage at 100.0%. The registry record does not explain the percentage’s denominator, event attribution, timing, or relationship to study treatment. The death count and serious event count do not establish that the treatment caused either event.
In general, adverse event counts need to be interpreted alongside exposure, follow-up, event definitions and attribution. These entries do not support a reliable comparison between the study arms or a broad safety rate estimate. The record does not provide additional detail that would resolve those limits.
12. What the Result Does, and Does Not, Mean
The record documents a study intended to characterize serum metabolites related to bone deposition, growth and turnover in metastatic CRPC, alongside listed clinical outcomes. It also identifies two denosumab-based treatment strategies. However, the record does not report a completed primary outcome result or a statistical analysis. It therefore does not show whether serum metabolite levels changed, how large any change was, or how precisely it was estimated.
Nor does the record establish a comparative effect between the arm labelled Alliance A031201 and the Standard of Care arm. Allocation was non-randomized, enrollment was 1, and the record does not identify the enrollee’s arm. The listed secondary outcomes are not accompanied by event-time or response results. No treatment benefit or lack of benefit can be inferred from those missing results.
The registry marks the study as terminated and describes the patient as having expired before completing the study. That information explains why the planned outcome record is incomplete only to the extent stated; the reason for termination and which measurements were collected are not reported. It would be inappropriate to infer why the patient expired or whether an intervention contributed.
In general, a small and incomplete study can still document feasibility questions or generate hypotheses, but its conclusions depend on what was measured and reported. The registry record does not provide enough observations or analysis detail to assess metabolomics feasibility, compare treatment strategies, or characterize clinical outcomes. The accurate interpretation is limited to the study design, its stated aims, and the sparse posted participant and adverse event information.
13. Why This Trial Matters Statistically
This study is statistically notable because its scientific aim and its available record do not align at the level of evidence needed for an outcome estimate. The stated primary question concerns repeated serum metabolite measurements, yet the registry reports that the patient expired before completing the study and gives no measurements or analysis. The gap between a clearly described biomarker question and an unavailable result is important when assessing what a registry entry can support.
The non-randomized allocation also matters. Even with more complete outcomes, a comparison between these arms would require careful attention to how participants entered each group and whether prognostic differences could explain observed contrasts. The registry record does not describe the allocation process or an adjustment strategy. In this record, enrollment of 1 and the absence of arm assignment information prevent a meaningful comparative assessment.
The entry also distinguishes planned outcomes from analyzed findings. Time to skeletal related event, progression-free survival and duration of response are listed, but no results are reported. The total number of outcome measures is 8, while full details for all measures are not given. This makes outcome completeness and multiplicity planning difficult to assess.
These features illustrate a general lesson in clinical biostatistics: a study title and endpoint description indicate questions of interest, not evidence that those questions were answered. Interpretation depends on observed data, analysis choices, uncertainty, and transparent accounting of missing outcomes. The registry record is informative about the study’s intended focus and limitations, but not about a treatment effect.
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 direct limitation is the enrollment of 1, alongside the registry statement that the patient expired before completing the study. The record does not say which scheduled metabolite measurements were obtained, whether the participant was assigned to either arm, or why the study was terminated. Without those details, even a descriptive account of the primary endpoint is unavailable.
Allocation is non-randomized and masking is listed as none. The record does not describe the allocation mechanism, eligibility criteria in detail, treatment exposure, adherence, or any methods intended to address confounding. The arm labels and treatment descriptions alone do not show that the groups were comparable. The record also does not report a trial-specific sample-size justification.
Key endpoint details are missing: the unit, parameter, dispersion measure, metabolite definitions, and analysis method are not reported. The record lists 8 outcome measures but names only the primary outcome and three secondary outcomes in the available descriptions. It does not report a multiplicity plan, missing-data approach, analysis populations, or protocol deviations.
There are no listed statistical analyses or outcome estimates. As a result, readers cannot assess effect magnitude, precision, model assumptions, or robustness. Safety information is similarly limited: the registry does not report event attribution, timing, or the denominator underlying the serious-term percentage. The serious adverse event counts do not permit a reliable comparison. These limitations are specific to the available registry record and should not be filled in by assumptions about the unreported protocol or conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Denosumab Plus Enzalutamide, Abiraterone and Prednisone Compared to Denosumab Plus Enzalutamide Alone for Men With Castrate Resistant Prostate Cancer (CRPC) With Bone Metastases — NCT02758132.
- Registry record last updated 2019-11-08; status last verified 2019-11.
- Results first posted 2019-10-02.
- 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.
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18. Record Summary
NCT02758132 is a phase 2, parallel, non-randomized, unmasked study sponsored by the University of Hawaii. It is listed as terminated, with an enrollment of 1. The study title describes denosumab plus enzalutamide, abiraterone and prednisone compared with denosumab plus enzalutamide alone. Its primary outcome concerns serum metabolites related to bone deposition, growth and turnover measured using GC-TOFMS.
The registry record lists measurement timepoints prior to registration, at registration, and on Day 1 of cycle 4 and 13. It names secondary outcomes for skeletal related events, progression-free survival and duration of response. The primary outcome population is described as a patient who expired before completing the study. No statistical analyses or outcome results are listed.
The record reports one serious event and one death in the Standard of Care group, and zero participants at risk in Alliance A031201. It does not provide sufficient outcome or analysis information to estimate a treatment effect or assess comparative safety.