Leuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Leuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer (NCT01163084), a randomized phase 1, phase 2 study. The primary outcome is Proportion of Patients With =< 5% Tumor Involvement.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group phase Ib/II study of preoperative vismodegib plus androgen ablation compared with androgen ablation alone. The official title identifies radical prostatectomy as the surgery following the preoperative treatment. The registry lists enrollment of 10. The record does not report the allocation ratio or describe how the random sequence was generated or concealed.

In the vismodegib group, participants received leuprolide acetate by intramuscular injection or goserelin acetate subcutaneously on day 1, with vismodegib taken orally once daily on days 1–28. Cycles were to repeat every 28 days for up to 16 weeks, unless disease progression or unacceptable toxicity occurred. The comparison group received leuprolide acetate or goserelin acetate on the same stated schedule, without vismodegib. The registry does not report whether all participants completed the planned treatment or underwent surgery.

The study started on 2010-07-09, and the listed primary completion date is 2012-06-01. Its status is terminated. The reason for termination, the timing of termination, and whether the study stopped before or after planned enrollment are not reported in the registry record. The phase designation is phase Ib/II, but the registry does not describe separate phase-specific objectives or decision criteria. Masking was listed as none, so the record describes the trial as open-label rather than blinded.

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: 10 participants started but only 9 were randomized

Overall Study

Analysis population for the primary outcome, as defined in the registry: Results was not determined.

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 With =< 5% Tumor Involvement, measured over Baseline up to 4 months or radical prostatectomy, whichever comes first.

The primary endpoint was the proportion of patients whose tumor involvement was 5% or less. The registry says pathologic staging would be assessed from samples collected at prostatectomy. Its stated timeframe was baseline up to 4 months or radical prostatectomy, whichever came first. The registry does not further define how tumor involvement was measured, how borderline or missing pathology findings would be handled, or how patients without a prostatectomy specimen would enter the endpoint analysis.

A pathologic measure after surgery can describe tumor involvement in the tissue examined, rather than relying only on assessments made before treatment. In this study, the endpoint was intended to compare the proportion meeting the specified threshold between the two randomized groups. That kind of binary endpoint reduces each patient’s pathology finding to whether it falls on one side or the other of a cutoff. Such a summary can be easier to compare between groups, but it also does not retain all the detail in the underlying pathology measurements.

The registry says results were to be descriptively summarized and that a two-sided Chi-Square test would test the difference between the groups. However, the primary outcome result was not determined in the registry record. No group counts, proportions, effect estimate, confidence interval, or test result for this endpoint are reported there.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies randomization, an open-label parallel-group design, and a planned two-sided Chi-Square test for the primary comparison. It does not report a detailed statistical analysis plan, a sample-size justification for the trial, or analysis results. The explanations below describe the methods in general and distinguish the stated plan from results that are absent from the registry record.

What does randomization contribute?

In general, randomization assigns participants to groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the time of assignment, so that outcome comparisons can be interpreted more fairly. Randomization does not guarantee that groups will be similar in every characteristic, especially in a small study. The registry says the study was randomized, but the sequence-generation method, allocation concealment, and allocation ratio are not reported in the registry record.

What does the Chi-Square test assess?

In general, a Chi-Square test can assess whether the distribution of categorical outcomes differs between groups. Here the stated outcome is whether a patient’s tumor involvement was 5% or less, and the planned test was two-sided. A two-sided test considers evidence of a difference in either direction; it does not establish which group has the higher proportion without the group results. The registry does not report the outcome counts or the test statistic, so no test conclusion can be drawn.

Chi-Square methods rely on information about the counts in the outcome categories. When cell counts are sparse, the usual approximation may be unreliable, and an exact method or another approach may be considered in general. The study enrolled 10 participants, but the registry does not report the endpoint category counts or evaluable sample size. It is therefore not possible to determine from the record whether the planned test’s assumptions were met or whether another method was used.

What would an effect estimate and confidence interval add?

In general, an effect estimate describes the observed comparison between groups, while a confidence interval describes the range of values compatible with the data under the method’s assumptions. The interval communicates precision as well as direction and magnitude. A wide interval would indicate substantial uncertainty; a narrow interval would indicate greater precision. No primary effect estimate or confidence interval is reported in the registry record, so neither the magnitude nor the precision of the planned comparison can be assessed.

How should the planning illustrations be read?

The registry’s planning illustration describes a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It frames the effect to detect as a stated fraction of the observed effect. These are assumptions for planning illustrations, not a reported account of how the original trial’s enrollment was chosen. The record does not report the trial’s own sample-size justification.

Sample-size illustrations estimate how many participants per arm might be needed under specified assumptions. They are not observed power and do not show what the trial found. Because the primary outcome result was not determined in the registry record, the illustrations should not be read as a substitute for an observed comparison. The numerical planning outputs do not establish the achieved precision of this study.

The record lists zero analysis results. It does not provide a primary test result, an analysis population definition, a missing-data method, or details about any adjusted analyses. The test named in the endpoint description is the only specific inferential method described for that outcome. Whether analyses beyond the stated descriptive summary and Chi-Square test were conducted is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description specifies a two-sided Chi-Square test for a comparison between the two groups. The registry does not report a broader statistical analysis plan, a hierarchy of primary and secondary hypotheses, or any method for controlling multiplicity. It lists 8 outcome measures, but does not explain how testing across those outcomes was to be interpreted or whether any multiplicity adjustment was planned. Without that information, the record does not establish how the chance of false-positive findings across multiple analyses would have been addressed.

The registry does not report an analysis population definition, such as whether the primary analysis was intended to follow participants according to randomized assignment. It also does not report how participants without usable prostatectomy pathology, participants who did not complete treatment, or participants with missing outcome data would be handled. The endpoint timeframe includes baseline up to 4 months or surgery, whichever came first, but that alone does not specify a missing-data strategy.

The record does not report the number of participants with evaluable primary endpoint data, the extent or reasons for missing data, or any sensitivity analyses. It also does not describe interim analyses or early stopping rules. These items are not reported in the registry record; their absence from the record does not establish whether they were or were not used outside the posted record.

These omissions matter because the interpretation of a small randomized study depends on who was included in each analysis and how incomplete outcome information was handled. With no primary result, no analysis population, and no missing-data account reported, it is not possible to assess whether the posted outcome information would represent all randomized participants or a subset.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for participants at risk in each group. In the group receiving vismodegib with androgen ablation, 4 participants were at risk and 0 were recorded as affected by serious adverse events. In the androgen-ablation-alone group, 5 participants were at risk and 0 were recorded as affected by serious adverse events. Deaths were listed as 0 in each group.

The registry also lists other adverse events: 4 participants were at risk and 4 were affected in the vismodegib group, while 5 were at risk and 5 were affected in the androgen-ablation-alone group. The record does not provide the event terms, event severity, number of events per participant, or a description of how these “other” events are distinguished from serious adverse events. No serious adverse-event terms are listed.

These figures are counts, not comparative estimates. The at-risk counts are small, and the registry does not report a statistical safety comparison or further follow-up detail. Zero recorded serious events or deaths in these groups should be read as the reported observations, not as proof that such events could not occur or that the groups have equivalent safety.

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

The record establishes that a randomized, open-label phase Ib/II study was planned to compare preoperative androgen ablation with the same approach plus vismodegib, followed by radical prostatectomy. It also specifies a primary pathology endpoint and a planned comparison method. Those design details describe the question the trial set out to address; they do not supply an answer to that question.

The primary outcome was not determined in the registry record. Consequently, the record does not show whether either group had a higher proportion of patients with tumor involvement of 5% or less. It gives no estimate of the between-group difference, no confidence interval, and no p-value for the primary comparison. The findings therefore cannot support a conclusion about the size, direction, or statistical precision of a difference in this endpoint.

The status “terminated” does not explain why the study ended, and the registry does not identify a reason for termination. It is not possible to infer from that status whether the study ended for administrative, recruitment, safety, efficacy, or other reasons. Likewise, the absence of a determined primary result should not be interpreted as a null finding or as evidence that the treatments were equivalent.

The adverse-event counts provide limited descriptive information. They show the listed counts of participants affected by serious and other adverse events and the deaths recorded, but do not describe event types or provide a formal between-group safety analysis. The small at-risk groups and the limited event detail make those counts insufficient for a broad comparative safety conclusion.

In general, a randomized design can support a comparative interpretation when the outcomes, analysis population, and methods are reported. In this record, those elements are incomplete for the primary endpoint. The most defensible reading is that the trial’s intended comparison is documented, while its primary result and the reasons for termination are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates the difference between a registered research question and a reported answer. The registry describes randomization, two treatment strategies, a pathology-based primary endpoint, and a planned statistical test. Yet the primary result was not determined in the registry record. Without outcome counts and an estimate of the between-group comparison, the central statistical question remains unanswered in the posted record.

The study also highlights the importance of reporting who contributed data to each analysis. Enrollment was 10, while the safety groups list 4 and 5 participants at risk. The record does not explain the relationship between those figures or report the number with evaluable primary pathology. A reader needs that context to understand the analysis denominator and the degree to which the outcome reflects the randomized groups.

Small studies can be useful for evaluating feasibility and generating information, but their estimates may be imprecise, and sparse categorical outcomes can complicate standard testing. These are general statistical considerations; the registry does not report enough primary outcome data to determine their practical impact in this study. The planning illustrations are not substitutes for an observed result or a trial-specific sample-size justification.

Finally, the terminated status and incomplete outcome record underscore why status alone cannot explain a study’s evidence. A clear account of termination, outcome availability, analysis populations, and statistical methods would help readers distinguish an unreported result from a completed analysis showing little evidence of a difference. Those details are not reported in the registry record.

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 principal limitation is that the primary outcome result was not determined in the registry record. No group-specific primary outcome counts, proportions, effect estimate, confidence interval, or p-value are reported. This prevents assessment of the direction, size, and precision of the intended comparison.

Enrollment was 10, and the record does not report the number of participants with evaluable prostatectomy samples or the number included in the primary analysis. It does not explain whether participants who did not proceed to surgery or lacked pathology data were excluded, retained, or handled in another way. The reason for termination is also not reported, so the study’s completion and outcome-reporting context remain unclear.

The registry states that a two-sided Chi-Square test was planned, but does not provide the outcome counts needed to assess whether its assumptions were appropriate. It does not report randomization details, allocation ratio, an analysis population, missing-data methods, an adjustment strategy for multiple outcomes, or interim-analysis plans. The record also does not describe the threshold measurement procedures in enough detail to assess how tumor involvement was classified.

Safety reporting is limited to counts at risk and counts affected by serious or other adverse events, along with deaths. The event terms and further clinical detail are not reported. These limitations constrain both the comparative interpretation and the ability to understand what the recorded safety counts represent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Leuprolide Acetate or Goserelin Acetate With or Without Vismodegib Followed by Surgery in Treating Patients With Locally Advanced Prostate Cancer — NCT01163084.
• Registry record last updated 2019-02-28; status last verified 2019-02.
• Results first posted 2019-02-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01163084 was a randomized, open-label, parallel-group phase Ib/II study sponsored by the National Cancer Institute. It compared leuprolide acetate or goserelin acetate before surgery, with or without vismodegib, in patients with locally advanced prostate adenocarcinoma. The study enrolled 10 participants, started on 2010-07-09, listed primary completion on 2012-06-01, and has a terminated status.

The primary endpoint was the proportion of patients with 5% or less tumor involvement based on prostatectomy samples. A two-sided Chi-Square test was planned, but the primary result was not determined in the registry record. The record lists no analysis results and does not state why the study was terminated. Safety counts include no serious adverse events or deaths in either listed group, alongside other adverse events recorded in both groups.