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 Immediate Prostatectomy vs. Cabozantinib Followed by Prostatectomy in Men With High-Risk Prostate Cancer (NCT03964337), a randomized phase 2 study. The primary outcome is Apoptotic Index in Prostatectomy Specimens From Patients Who Undergo Immediate Prostatectomy (Arm B) Versus Those Treated With Cabozantinib Followed by Prostatectomy (Arm A).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03964337 |
| Phase | Phase 2 |
| Condition | Prostate Cancer, Prostate Cancer Adenocarcinoma, Non-Metastatic |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Duke University |
| Results posted | Yes |
2. Clinical Question
Population
Men with untreated, high-risk, non-metastatic prostate cancer undergoing radical prostatectomy. The registry record reports 3 participants enrolled, while the study description had planned to enroll 30 subjects.
Intervention
Cabozantinib 40 mg by mouth daily for 4 weeks, followed by a 2 week drug washout before prostatectomy. The treatment arm is described as cabozantinib followed by prostatectomy.
Comparator
Immediate prostatectomy, described in the protocol summary as surgery within 12 weeks of registration. The record identifies this as the control group.
Primary question
Whether the pathologic apoptotic index, measured by cleaved caspase-3 levels in tumor tissue at prostatectomy, differs between the immediate-prostatectomy group and the group receiving cabozantinib before surgery.
This is a comparison of a tissue-based biological measure at surgery, not a reported comparison of survival, symptoms, or another clinical outcome. The registry record also describes secondary immune profiling in peripheral blood and the tumor microenvironment. It does not report collected primary outcome data or an estimated difference between the groups, so the clinical question remains unanswered by the posted results.
3. Trial Design
The registry record describes SPARC as a phase II, open-label, randomized study with a parallel-group design. Participants were intended to undergo either cabozantinib followed by prostatectomy or immediate prostatectomy. Because masking was absent, participants and study personnel were not blinded to the assigned approach.
The planned study was to enroll 30 subjects. The summary describes a 2:1 allocation plan, with 20 assigned to cabozantinib followed by prostatectomy and 10 to immediate prostatectomy. It also describes a safety lead-in cohort of the first 9 subjects: 6 assigned to cabozantinib and 3 to immediate prostatectomy. These first participants were to be assigned, while later participants were to be randomized. Accrual at an additional site was contingent on six cabozantinib participants completing the 57-85 day safety visit without triggering a stopping rule.
The planned cabozantinib schedule was 40 mg by mouth daily for 4 weeks, followed by a 2 week washout before prostatectomy. The immediate-prostatectomy group was to undergo surgery within 12 weeks of registration. The primary endpoint was to be assessed at prostatectomy, with the timeframe described as Arm A: Day 43 and Arm B: Day 1.
Actual enrollment was 3. The study status is terminated, and the record gives a primary completion date of 2021-06-04. The reason for termination and the details of any changes to the planned conduct are not reported in the registry record. The planned allocation and enrollment targets therefore describe the design intent, not the distribution or experience of a completed trial.
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: Study accrual was discontinued prior to enrolling any participants in the control arm (Immediate Prostatectomy, Arm B).
Overall Study
| Stage | Cabozantinib Followed by Prostatectomy (Arm A) | Immediate Prostatectomy (Arm B) |
|---|---|---|
| STARTED | 3 | 0 |
| COMPLETED | 3 | 0 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Data not collected.
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: Study accrual was discontinued prior to enrolling any participants in the control arm (Immediate Prostatectomy, Arm B).
| Characteristic | Unit | Cabozantinib Followed by Prostatectomy (Arm A) | Immediate Prostatectomy (Arm B) | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 0 | 3 | |
| Age, Continuous | years | 62.47 (SD 8.40) | — | 62.47 (SD 8.40) |
| Sex: Female, Male: Female | Participants | 0 | — | 0 |
| Sex: Female, Male: Male | Participants | 3 | — | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | — | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | — | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | — | 0 |
| 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 | 3 | — | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | — | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | — | 0 |
| Region of Enrollment: United States | Participants | 3 | — | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Apoptotic Index in Prostatectomy Specimens From Patients Who Undergo Immediate Prostatectomy (Arm B) Versus Those Treated With Cabozantinib Followed by Prostatectomy (Arm A), measured over At prostatectomy (Arm A: Day 43, Arm B: Day 1).
| 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 the apoptotic index in prostatectomy specimens. The registry defines this measure as cleaved caspase-3 levels in tumor tissue, assessed at prostatectomy. The planned comparison is between participants undergoing immediate prostatectomy and participants who receive cabozantinib before prostatectomy.
General biological explanation: apoptosis is a process of programmed cell death, and cleaved caspase-3 is used as a tissue marker associated with that process. Measuring it in the removed tumor provides a way to examine a biological response in the tissue after the assigned treatment approach. It is a laboratory or pathology endpoint, rather than a direct measure of how participants feel, function, or survive.
The registry record does not state a unit, summary parameter, or dispersion measure for the endpoint. It lists the primary outcome population as “Data not collected.” No group-level values, between-group estimate, confidence interval, or significance test are posted. Consequently, the intended endpoint and its measurement are described, but the registry record does not establish whether the groups differed in apoptotic index or how precisely any difference could be estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The most important statistical fact is that the registry record lists actual enrollment as 3 and states that primary outcome data were not collected. No primary endpoint comparison is reported. There is therefore no posted estimate of the difference in cleaved caspase-3 levels between the two treatment groups, and no confidence interval or p-value with which to assess its direction, magnitude, or precision.
This should not be read as evidence that the approaches had the same apoptotic index. A missing estimate is not an estimate of no difference. Nor does the absence of a reported statistical test establish that a test found no statistically significant result. The registry record lists zero analyses, and the primary outcome population is explicitly recorded as data not collected.
Actual enrollment was substantially short of the planned enrollment of 30 subjects, but the registry record does not explain the reasons or give a detailed account of how the enrolled participants were distributed across groups. The adverse-event summary lists 3 participants at risk in the cabozantinib-followed-by-prostatectomy group and 0 in the immediate-prostatectomy group. These figures do not provide a basis for comparing the groups on the primary endpoint, and the zero at-risk count for the immediate-surgery group makes a safety comparison especially limited.
The planned design was intended to compare a biological tissue measure under two surgical pathways. The posted record documents that intention and a small amount of safety information, but it does not provide the observations needed to answer that comparison. The secondary immune phenotyping outcomes are named, but no analysis results are reported for them either.
As a result, interpretation should focus on what the record can support: the trial was designed as a randomized phase II study, enrollment was 3, the status is terminated, and primary outcome data were not collected. Claims about the size or direction of a biological effect, its statistical uncertainty, or the clinical implications of such an effect are not supported by the posted results.
9. Statistical Methods Explained
General statistical explanation: A randomized parallel-group trial assigns participants to separate treatment strategies and compares outcomes between those groups. Randomization can help balance measured and unmeasured participant characteristics on average, but its protections depend on how allocation is implemented and on having outcome data to analyze. This record describes a planned randomized study, with the first 9 subjects assigned as a safety lead-in and later subjects intended to be randomized. Since actual enrollment was 3 and primary outcome data were not collected, the planned comparative analysis cannot be evaluated from posted primary results.
What would the primary comparison estimate?
The primary outcome is an apoptotic index measured by cleaved caspase-3 levels in tumor tissue at prostatectomy. A comparative analysis would ordinarily summarize that measure for each group and estimate a difference between the groups, using a method appropriate to the scale and distribution of the outcome. The registry record does not state the unit, summary parameter, or dispersion measure, and it does not report an analysis method for the primary outcome. It is therefore not possible to identify a planned model, adjustment strategy, or particular effect measure from the record.
General statistical explanation: An effect estimate describes the observed contrast between groups; a confidence interval describes the uncertainty around that estimate under the assumptions of the analysis. A p-value, when reported, measures how compatible the observed data are with a specified statistical null model. None of these quantities is reported for the primary endpoint in this registry record. Without an estimate and its uncertainty, statistical significance and precision cannot be assessed.
Why does the small enrollment matter?
The study planned to enroll 30 subjects but reports actual enrollment of 3. A small study generally has less information for estimating group differences, and its estimates can be highly uncertain. In this record, however, the more direct limitation is that the primary outcome data were not collected: there is no posted primary estimate to interpret, whether precise or imprecise. Enrollment alone does not reveal an outcome effect, and it should not be used to infer one.
The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are not a description of the trial's own design justification. The planned study allocation was 2:1, and the record does not report a trial-specific sample-size justification. Planning sample sizes should not be interpreted as observed power or as evidence that a result was obtained.
What does over-dispersion mean in general?
General statistical explanation: Over-dispersion occurs when variability in observed outcomes is greater than the variability assumed by a statistical model. If it is ignored, standard errors can be too small and confidence intervals can be too narrow. Whether this issue is relevant depends on the outcome and analysis model. The registry record does not report a primary outcome model or enough outcome data to assess dispersion, so over-dispersion cannot be evaluated for this trial.
How should the design features be read?
The study was open-label and had no masking. General statistical explanation: Knowledge of treatment assignment can influence care, co-interventions, assessments, or reporting, particularly for outcomes involving judgment. A pathology measure may be more objective than a subjective report, but the record does not say whether specimen assessment was blinded or how measurements were standardized. Those procedural details are not reported in the registry record.
The safety lead-in was designed to permit an accrual decision after six cabozantinib participants completed a 57-85 day safety visit without triggering a stopping rule. That is a planned safety condition, not a reported interim efficacy analysis. Whether an interim efficacy analysis occurred, and the details of any interim statistical procedures, are not reported in the registry record. The presence of a safety lead-in alone does not establish that early efficacy testing or statistical stopping boundaries were used.
Can secondary analyses be interpreted?
The record names immune phenotyping and immunohistochemical outcomes, including measurements involving myeloid-derived suppressor cells, neutrophils, macrophages, CD8+, PD-L1, CTLA-4, and IL-1RA. It lists 14 outcome measures but reports zero analyses. No results, effect estimates, confidence intervals, or p-values are posted for these outcomes.
General statistical explanation: When several outcomes or comparisons are tested, the chance of obtaining at least one apparently unusual result can increase. Multiplicity procedures can address this issue, but their choice depends on which outcomes are confirmatory, how tests are related, and how the analysis plan is defined. The registry record does not report a multiplicity adjustment or a hierarchy of confirmatory and exploratory outcomes. With no posted analyses, there is also no observed set of tests for which to assess adjustment.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 14 outcome measures, including the primary apoptotic index and secondary immune phenotyping and immunohistochemical outcomes. It reports zero analyses. No statistical approach for handling multiple outcomes, comparisons, or time points is reported in the registry record. The record therefore does not establish whether any outcomes were designated as confirmatory, whether a testing hierarchy was planned, or whether an adjustment for multiplicity was intended.
General statistical explanation: If many outcomes are tested, the chance of at least one result appearing noteworthy by chance can rise. A multiplicity strategy may control that risk, but it must be specified in relation to the planned tests and interpretation. Since no results or analysis details are posted, multiplicity cannot be assessed from the registry record.
The primary outcome population is recorded as “Data not collected.” The registry record does not describe missing-data handling, imputation, sensitivity analyses, or reasons for missing primary outcome data. It also does not specify an intention-to-treat, per-protocol, or safety analysis population for efficacy comparisons. The planned groups and the participants at risk in the adverse-event summary do not substitute for a reported analysis population.
These omissions matter because a statistical result depends not only on the outcome definition but also on which participants and measurements are included and how missing observations are handled. Here, the absence of collected primary outcome data means there is no primary analysis whose population, missing-data assumptions, or multiplicity treatment can be checked.
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 |
|---|---|---|---|
| Cabozantinib Followed by Prostatectomy (Arm A) | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cabozantinib Followed by Prostatectomy (Arm A) | 0 of 3 |
| Immediate Prostatectomy (Arm B) | 0 of 0 |
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 |
|---|---|
| Cabozantinib Followed by Prostatectomy (Arm A) | 3 of 3 |
| Immediate Prostatectomy (Arm B) | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cabozantinib Followed by Prostatectomy (Arm A) | Immediate Prostatectomy (Arm B) |
|---|---|---|---|
| Constipation | Gastrointestinal disorders | 3 of 3 | 0 of 0 |
| Abdominal pain | Gastrointestinal disorders | 2 of 3 | 0 of 0 |
| Fatigue | General disorders | 2 of 3 | 0 of 0 |
| Urinary incontinence | Renal and urinary disorders | 2 of 3 | 0 of 0 |
| Skin and subcutaneous tissue disorders - Other | Skin and subcutaneous tissue disorders | 2 of 3 | 0 of 0 |
| Anemia | Blood and lymphatic system disorders | 1 of 3 | 0 of 0 |
| Diarrhea | Gastrointestinal disorders | 1 of 3 | 0 of 0 |
| Nausea | Gastrointestinal disorders | 1 of 3 | 0 of 0 |
| Pain | General disorders | 1 of 3 | 0 of 0 |
| Hepatobiliary disorders - Other | Hepatobiliary disorders | 1 of 3 | 0 of 0 |
The adverse-event summary lists the cabozantinib-followed-by-prostatectomy group with 3 participants at risk for serious adverse events, 0 participants affected by serious adverse events, 3 participants at risk for other adverse events, 3 participants affected by other adverse events, and 0 deaths. The immediate-prostatectomy group lists 0 participants at risk and 0 affected for both serious and other adverse events, with 0 deaths.
These counts should be read with the group sizes at risk in mind. In particular, the immediate-prostatectomy row reports 0 participants at risk, so it does not provide an observed comparison group for interpreting safety. A zero count among participants at risk is also not equivalent to evidence that an event could not occur. The record does not identify the non-serious or other adverse events in this summary, and it does not list any top serious adverse-event terms.
The small number of participants represented and the absence of a safety comparison limit what can be concluded. These figures describe the posted safety record; they do not establish comparative safety or a broader rate of adverse events.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase II study intended to compare cabozantinib before prostatectomy with immediate prostatectomy in men with high-risk prostate cancer. Its primary endpoint was a tissue-based apoptotic index measured by cleaved caspase-3 levels at surgery. The study planned to enroll 30 subjects, reports actual enrollment of 3, and is listed as terminated.
The record does not report primary outcome data. It therefore does not show whether the apoptotic index was higher, lower, or similar in the two groups. No effect estimate, confidence interval, or p-value is posted. The absence of those statistics means the biological comparison cannot be quantified, and the result cannot be interpreted as either evidence for a difference or evidence of no difference.
The registry record also names secondary immune measures, but reports zero analyses. Their inclusion in the study description does not mean that results were obtained or that the measures changed. The limited adverse-event counts are not a substitute for the primary outcome and do not support a balanced comparison between groups.
General statistical explanation: A treatment-effect conclusion requires outcome data and an analysis that estimates the contrast between the assigned strategies, with uncertainty and relevant study limitations made clear. A trial design describes the question researchers intended to answer; it is not itself evidence of the answer. In this case, the posted information supports a description of the study plan, enrollment, status, and recorded adverse-event counts, but not a conclusion about the effect of cabozantinib on tumor apoptosis or other outcomes.
13. Why This Trial Matters Statistically
This trial is statistically notable because it set out to compare a biological endpoint in surgical specimens within a randomized phase II design, yet the registry record reports actual enrollment of 3 and primary outcome data not collected. That distinction illustrates a basic principle of trial interpretation: a clearly specified research question does not become an estimated treatment effect unless relevant outcomes are observed and analyzed.
The study description also separates a safety lead-in from later planned randomization. This is important when reading the design: the first 9 subjects were described as assigned to the two groups, while later participants were intended to be randomized. The registry record reports actual enrollment far below the planned 30 subjects, but does not report the reason for termination or explain how the planned conduct changed.
The named primary and secondary measures reflect different kinds of evidence. Cleaved caspase-3 in tumor tissue is a biological endpoint, while immune phenotyping describes additional cellular and immunohistochemical measures. Such endpoints can help characterize biological processes, but they do not by themselves supply evidence about clinical outcomes. Statistical interpretation must remain tied to what was measured and what was actually reported.
Finally, the record highlights why reporting analysis populations, missing-data methods, and multiplicity plans matters. Without primary observations or reported analyses, readers cannot evaluate effect size, precision, assumptions, or the consequences of testing multiple outcomes. The statistical lesson is not that the trial found a particular result; it is that the available record does not contain the outcome evidence needed to answer its primary question.
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 main limitation for interpreting this particular trial is that the registry record states that primary outcome data were not collected. Actual enrollment was 3, compared with the planned enrollment of 30 subjects. No primary endpoint values, group comparison, confidence interval, or p-value are reported. Consequently, there is no observed estimate from which to assess direction, magnitude, or precision.
The record lists the study status as terminated but does not report the reason for termination. It also does not give a detailed account of participants' treatment assignments, completion of surgery, or the reasons outcome data were not collected. The planned safety lead-in and accrual condition are described, but the record does not say whether or when the additional site opened or whether the planned expansion proceeded.
Important analysis details are also absent from the registry record: the primary outcome's unit and summary parameter, the statistical model, the analysis population, missing-data procedures, and any multiplicity plan. The record does not report whether pathology assessment was blinded or how the tissue measure was standardized. These gaps prevent evaluation of how a primary comparison would have been constructed even if results were posted.
The adverse-event summary is limited by the small number of participants and by the immediate-prostatectomy group having 0 participants at risk. The record does not identify the other adverse events or provide a usable comparative safety assessment. These limitations concern the posted record and do not establish why the study stopped or what its unreported outcomes might have been.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immediate Prostatectomy vs. Cabozantinib Followed by Prostatectomy in Men With High-Risk Prostate Cancer — NCT03964337.
- Registry record last updated 2022-06-29; status last verified 2022-06.
- Results first posted 2022-06-29.
- 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
The registry record describes NCT03964337, a phase II, open-label, randomized parallel-group study comparing cabozantinib followed by prostatectomy with immediate prostatectomy in men with high-risk prostate cancer. The planned enrollment was 30 subjects, with a 2:1 allocation plan and a safety lead-in among the first 9 subjects. Actual enrollment was 3, and the study status is terminated.
The primary endpoint was apoptotic index in prostatectomy specimens, measured by cleaved caspase-3 levels in tumor tissue. The record states that primary outcome data were not collected and reports zero analyses. It names secondary immune and tissue outcomes but does not report their analysis results. The reason for termination and key statistical details, including missing-data handling and analysis populations, are not reported in the registry record.