Cabozantinib in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cabozantinib in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) (NCT04631744), a na phase 2 study. The primary outcome is Median Radiographic Progression-free Survival (rPFS) Using Kaplan-Meier Methodology.

2. Clinical Question

The study focuses on a selected group rather than all patients with metastatic castrate resistant prostate cancer. The official title specifies patients with known amplifications or activating mutations in gene targets of cabozantinib, or patients with liver metastases, after prior anti-androgen therapy. The brief description frames the hypothesis as anti-tumor activity in a molecularly selected group or in patients with liver metastases. The registry record does not further report the molecular eligibility details or the number of participants in each eligibility subgroup.

The primary outcome is a time-to-event measure: the elapsed time from starting treatment until radiographic progression. The registry record names secondary outcomes covering prostate-specific antigen change, overall survival, tumor response, and adverse events. It does not report results for the primary or secondary outcomes in the record details available for this analysis. Consequently, the clinical question is specified, but the posted information does not establish what was observed for radiographic progression-free survival or the other outcomes.

3. Trial Design

This is an open-label phase II study of cabozantinib in metastatic castrate resistant prostate cancer. It is listed as a single-group trial, with no masking and allocation recorded as not applicable. No comparator arm is described, so the design does not support a direct, randomized comparison with another treatment or with a control group. The registry lists Weill Medical College of Cornell University as the sponsor.

The registry record lists enrollment of 4. It also states that one participant withdrew after being registered but before starting treatment. The record does not explain why the study was terminated, how many participants received treatment, or whether any other participants withdrew or were excluded from an analysis. The study start date is 2021-03-03, the primary completion date is 2025-05-12, and its status is terminated. These registry entries describe the recorded study status and timeline; they do not give a reason for termination.

The intended population comprised patients with metastatic castrate resistant prostate cancer who had received prior anti-androgen therapy and met the molecular or liver-metastasis selection described in the official title. The registry record does not report the exact eligibility thresholds or other inclusion and exclusion criteria. Its brief description states the hypothesis of anti-tumor activity in a molecularly selected group or in patients with liver metastases, but a hypothesis is not an observed result.

The primary endpoint is median radiographic progression-free survival, assessed using Kaplan-Meier methodology. Radiographic progression was to be assessed using PCWG-modified RECIST 1.1 criteria for soft-tissue lesions and protocol-specific criteria for bone lesions. The registry record gives a timeframe of treatment initiation to a minimum of radiographic progression, approximately 6 months. It does not report the endpoint estimate, its confidence interval, or a detailed account of the analysis population. The registry record also does not report the study's sample-size justification, statistical analysis plan, or reason for termination.

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: 1 subject withdrew after being registered but before starting treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 1 participant withdrew after being registered but before starting treatment

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: 1 participant withdrew after registering but before starting treatment

6. Primary Endpoint

The registry lists the primary outcome as Median Radiographic Progression-free Survival (rPFS) Using Kaplan-Meier Methodology, measured over From initiation of treatment to minimum of radiographic progression, approximately 6 months..

The primary endpoint is median radiographic progression-free survival (rPFS), in months, estimated using the Kaplan-Meier method and accompanied by a 95% confidence interval. It measures the time from treatment initiation to radiographic progression. The registry's timeframe describes the period from treatment initiation to a minimum of radiographic progression, approximately 6 months. The endpoint description defines rPFS as time from treatment start to radiographic progression.

Radiographic progression was to be evaluated using PCWG-modified RECIST 1.1 criteria for soft-tissue lesions and protocol-specific criteria for bone lesions. For soft-tissue lesions, the description includes an increase of at least 20% in the sum of the longest diameters of target lesions, relative to the smallest sum since treatment began, or the appearance of new lesions. The record's wording also repeats the appearance of one or more new lesions. For bone lesions, the criteria distinguish whether new lesions are present; new lesions are to be confirmed on a second scan performed 6 or more weeks later.

General statistical context: a time-to-event endpoint retains information about when an event occurs, rather than reducing follow-up to whether a participant experienced the event. The median is the time by which the estimated event-free proportion reaches the midpoint of the survival curve. A confidence interval expresses uncertainty around that estimate. The registry record specifies this endpoint and method, but does not report a median rPFS estimate or its confidence interval. Therefore, the endpoint's observed value and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: the primary outcome is a time-to-event endpoint. Each participant contributes follow-up from the stated time origin, treatment initiation, until the event of interest or the end of observed follow-up. The registry defines the event as radiographic progression. Time-to-event methods are useful when participants can have different follow-up durations and when the timing of an event matters. The record does not report individual participant follow-up times or how follow-up ended for each participant.

What does Kaplan-Meier estimation do?

General statistical context: the Kaplan-Meier method estimates the probability of remaining free of the event over time. It updates the estimate at observed event times and can incorporate censored follow-up, meaning a participant's event time is not observed during the available observation period. Censoring does not mean that an event did not occur; it means that the event status or timing is not known beyond the participant's recorded follow-up. The registry says that Kaplan-Meier methodology is used, but does not report the censoring rules, the number of censored observations, or the follow-up distribution.

The median rPFS is the point on the estimated curve at which the estimated proportion remaining free of radiographic progression reaches one half. It is a summary of the estimated time-to-event distribution. If too little follow-up or too few events are available, a median may be difficult to estimate; the registry record does not report whether this occurred. No median estimate or confidence interval is reported in the registry entries available for this analysis.

What does the confidence interval communicate?

General statistical context: a confidence interval conveys the uncertainty associated with an estimate under the method's assumptions. A narrower interval indicates greater precision, while a wider interval indicates less precision. It is not a range containing a known, fixed fraction of individual participants' event times, and it does not remedy weaknesses in the study design. The registry specifies a 95% confidence interval for the primary endpoint, but does not report its limits. Because the estimate and interval are absent, their magnitude and precision cannot be assessed.

How was progression defined?

The registry specifies separate assessment approaches for soft-tissue and bone lesions. Soft-tissue progression follows PCWG-modified RECIST 1.1 criteria and includes an increase of at least 20% in the sum of longest diameters of target lesions relative to the smallest sum since treatment started, or the appearance of new lesions. The record's description repeats new-lesion appearance in its wording. Bone progression is described in terms of whether there are new lesions; new bone lesions require confirmation on a second scan performed 6 or more weeks later. These definitions determine which observations count as events in the rPFS analysis. The record does not provide the imaging schedule beyond this confirmation rule, nor does it report details of independent review or adjudication.

What can a single-group design estimate?

General statistical context: a single-group study estimates outcomes among the participants observed under the study conditions. It has no concurrent group to represent what would have happened over the same period under an alternative condition. A comparison with an external benchmark, if one were planned, would depend on details of the benchmark and analysis; no such comparison is described in the registry record. Since allocation is not applicable, there is no randomized allocation process to balance measured and unmeasured characteristics between treatment groups. Since the study is open label, participants and study personnel are not masked to the intervention according to the registry.

These design features are relevant to interpretation even when an endpoint is measured using a defined radiographic rule. Outcome definitions can improve consistency, but they do not create a control group, establish that observed events were caused by treatment, or eliminate all potential assessment differences. The registry record does not report further protections against assessment bias.

What do the planning assumptions describe?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event planning, the description refers to a total number of events, while other planning illustrations are expressed as participants per arm. These are planning assumptions, not a report of the trial's design or its actual sample-size justification. They do not represent observed power. The trial itself is listed as single group, not as an equal-allocation, two-arm comparison. No specific planning values are reported in the registry entries, and the protocol's sample-size justification is not reported in the registry record.

The registry lists zero analyses. It does not provide an inferential test, an effect estimate, or a statistical comparison for the primary endpoint. Sponsor-reported hazard ratios are not available in the record details, and the primary endpoint is a median rather than a reported hazard ratio. Any simple recalculation from summary statistics would require posted summary statistics that are not present. There is therefore no recalculated estimate to compare with a sponsor analysis.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study assesses several outcomes or performs multiple statistical tests. Repeated testing can increase the chance of observing a result that appears noteworthy even when there is no corresponding underlying effect. General statistical approaches include prespecifying a primary outcome, adjusting for multiple comparisons, or treating secondary analyses as exploratory. The registry names one primary endpoint and lists secondary outcomes for prostate-specific antigen change, overall survival, tumor response, and adverse events. It does not report a multiplicity adjustment, a hierarchy among the secondary outcomes, or the details of an analysis plan. These matters are not reported in the registry record.

The record lists five outcome measures and zero analyses, but does not provide results for the primary or secondary outcomes in the information available. The lack of posted analyses means that statistical significance, confidence intervals, and the treatment of multiple comparisons cannot be evaluated. It also does not establish whether analyses were planned but not completed, or whether results were recorded elsewhere; the reason is not reported in the registry record.

The record notes that one participant withdrew after registration but before treatment. It does not describe missing outcome data, censoring patterns, handling of participants who did not begin treatment, or the population used for analysis. In general, missing outcomes can affect both the amount of information available and the interpretation of an estimate, particularly if the reasons for missingness relate to prognosis or treatment experience. The registry record does not report the assumptions or methods used to address missing data.

The registry record also does not report whether interim analyses were planned or conducted, whether any stopping rules were specified, or whether the termination decision was related to efficacy, safety, feasibility, or another reason. These details cannot be inferred from the terminated status alone. No statistical analysis population is specified in the record details.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic failure (25.0%), pyleonephritis (25.0%), generalized weakness (25.0%).

The registry lists safety figures for the cabozantinib group. Four participants are listed as at risk for serious adverse events, and 2 are listed as affected. For other adverse events, 4 are listed as at risk and 4 as affected. The record lists 1 death. These are counts as recorded in the registry; they are not comparative estimates because there is no control group.

The most frequent serious adverse-event terms listed are Hepatic Failure, Pyleonephritis, and Generalized Weakness, each shown as 25.0%. The registry record does not clarify the relationship between these terms and the serious-event counts, nor does it provide event timing, severity grades, duration, or participant-level detail in the information available. It also does not report whether the events were judged related to cabozantinib. A listed event occurring during a study does not, by itself, demonstrate that the study treatment caused it.

The at-risk counts provide the denominators associated with the registry's safety summaries, but the record does not explain the precise safety observation period or confirm treatment exposure for each listed participant. The one participant who withdrew before starting treatment makes it especially important not to assume that enrollment and exposure populations are identical; the registry does not provide enough detail to reconcile those populations. These figures describe reported safety observations, not a complete characterization of risk or a comparison with another treatment.

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

The record establishes that a phase II study was designed to examine cabozantinib in a selected population with metastatic castrate resistant prostate cancer. It defines radiographic progression-free survival as the primary endpoint and describes how radiographic progression was to be assessed. It also records enrollment of 4, a withdrawal after registration but before treatment, selected safety counts, and a terminated study status. Those details help readers understand the intended question and the amount of information recorded.

The record does not report the primary rPFS estimate or its 95% confidence interval. Without those values, the observed time-to-event result and its precision cannot be described. The record also does not report results for the listed secondary outcomes. The stated hypothesis is not evidence that the hypothesized activity was observed. No conclusion about the direction or magnitude of an efficacy outcome can be drawn from the endpoint definition alone.

Even if a single-group outcome estimate were available, its interpretation would be limited by the absence of a concurrent comparator and the open-label design. Such a result could describe what happened among participants in the study, but it could not on its own establish what would have happened to comparable participants under another treatment strategy. The registry does not report a randomized comparison, and it does not provide the analysis details needed to assess potential sources of bias or missing outcome information.

The safety counts are also descriptive. The record lists serious and other adverse events, and a death, but does not report attribution or comparative safety data. These figures should not be interpreted as proof that cabozantinib caused a particular event, nor as a complete estimate of treatment risk.

Accordingly, the registry information supports a description of the study design, target population, endpoint definitions, and limited safety reporting. It does not support a quantified assessment of the primary endpoint, a treatment comparison, or a definitive account of why the study ended. The reason for termination and the missing outcome analyses are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it distinguishes an endpoint definition from an endpoint result. The registry specifies median radiographic progression-free survival, the time origin, and radiographic criteria, but does not report the estimated median or its confidence interval. A well-defined outcome is necessary for interpretation, but it is not a substitute for observed data.

The study also illustrates how design limits affect the questions that can be answered. A single-group, open-label study can document outcomes in the enrolled participants, but it does not create a concurrent counterfactual comparison. Without a comparator, the observed course cannot be directly contrasted with what would have occurred under another strategy. This distinction matters especially when a stated study hypothesis might otherwise be mistaken for a demonstrated result.

Enrollment of 4 and the recorded withdrawal before treatment highlight the importance of reporting the analysis population and outcome availability. The registry does not explain how many participants contributed to each endpoint analysis, how censoring was handled, or how missing data were addressed. These details are essential for interpreting a time-to-event estimate and its precision.

The record's planning assumptions provide another useful distinction: planning illustrations based on an observed effect are not the same as the study's own sample-size justification, and they are not observed power. Their stated assumptions describe a two-arm illustration even though the registered design is single group. Readers should therefore separate hypothetical planning calculations from the actual design and from results.

Finally, the safety counts show why denominator, exposure, event attribution, and comparison context matter. Registry counts describe reported observations, but do not establish causation or comparative risk. Taken together, the record demonstrates that sound statistical reading depends not only on named methods, but also on design, data completeness, analysis reporting, and the limits of the available evidence.

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 important limitation for interpreting outcomes is that the registry record does not report the primary rPFS estimate or its confidence interval. It also does not report results for the secondary outcomes, despite listing them. Without those results, the observed efficacy outcomes and their precision cannot be evaluated.

The study is single group and open label, with no concurrent comparator. The record therefore offers no randomized basis for comparing cabozantinib with another treatment. The enrollment is 4, and one participant withdrew after registration but before treatment. The registry does not report the number treated, the number included in each analysis, or the extent of follow-up. These omissions limit assessment of how complete and representative the outcome data are.

The official title describes molecular selection or liver metastases and prior anti-androgen therapy, but the registry entries do not specify exact eligibility criteria or the distribution of participants across those characteristics. This prevents a fuller description of the enrolled population and limits assessment of how broadly the recorded experience may apply.

Important analysis details are also absent. The registry record does not report its statistical analysis plan, sample-size justification, censoring rules, analysis population, missing-data methods, multiplicity approach, or interim analyses. It does not explain the reason for termination. The record's stated planning assumptions describe an illustrative two-arm calculation, not the actual single-group design, and do not provide a substitute for the missing protocol justification or outcome analyses.

Safety interpretation is limited by the absence of event timing, severity grades, attribution, exposure details, and a comparator. The listed counts are descriptive, and the registry does not establish whether events were considered related to treatment. These trial-specific limitations mean that the record supports a description of planned methods and selected observations, but not a full evaluation of efficacy, comparative safety, or the reasons the study ended.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cabozantinib in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) — NCT04631744.
• Registry record last updated 2026-05-01; status last verified 2026-04.
• Results first posted 2026-05-01.
• 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

NCT04631744 is an open-label phase II, single-group study of cabozantinib in patients with metastatic castrate resistant prostate cancer. The stated population had prior anti-androgen therapy and specified molecular features or liver metastases. Weill Medical College of Cornell University is listed as the sponsor. The study began on 2021-03-03, reached primary completion on 2025-05-12, and is listed as terminated.

Enrollment is listed as 4; one participant withdrew after registration but before treatment. The primary endpoint is median radiographic progression-free survival using Kaplan-Meier methodology, with a 95% confidence interval. The registry record does not report the endpoint estimate, its interval, secondary outcome results, or the reason for termination. Safety counts are listed for serious and other adverse events, along with 1 death, but attribution is not reported.