Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer (NCT01935934), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study sponsored by the National Cancer Institute. The registry record lists enrollment of 102 participants and a completed status. The study began on 2013-05-08, and primary completion was recorded as 2019-09-12. These dates describe the registry record; they do not by themselves establish when every analysis was conducted or reported.

All participants were assigned to the treatment group described in the record. They received cabozantinib s-malate at 60 mg by mouth once daily on days 1-28. Courses were scheduled to repeat every 28 days unless disease progression or unacceptable toxicity occurred. The registry lists no masking and no allocation procedure, consistent with the single-group design. It does not describe a concurrent control group.

The listed conditions include recurrent or metastatic endometrial cancer and several histologic and stage categories. The study’s broad condition list should not be treated as evidence that every category contributed the same number of participants or had separate outcome estimates. Such breakdowns are not reported in the registry record.

The primary endpoint was response rate, expressed as a participant count and defined with RECIST v1.0 criteria for target lesions assessed by CT. Assessments were scheduled at 12 weeks, then every 8 weeks during treatment, with follow-up up to 12 weeks after treatment for participants who discontinued due to toxicities; the stated maximum was 16 weeks. Secondary outcomes included overall survival and the number of participants with archival specimens that had C-met amplification or mutation. Detailed analysis methods and outcome estimates are not reported in the registry record.

A single-group phase 2 design can describe outcomes among treated participants, but it does not provide a randomized comparison. Any observed response count would therefore be a description of this study group, not a direct estimate of how outcomes would differ under another treatment.

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

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 Response Rate, measured over At 12 weeks, then every 8 weeks during treatment; up to 12 weeks post-treatment if discontinued due to toxicities, a maximum of 16 weeks.

The primary endpoint, response rate, is defined as the count of participants who achieved either a complete response or a partial response under RECIST v1.0 criteria for target lesions assessed by CT. A complete response requires disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. The registry defines overall response as complete response plus partial response.

Response is used in oncology studies as a way to characterize measurable change in target lesions over an assessment period. It is a binary classification at the participant level for the response definition: each participant either meets the stated response criteria or does not. A count can then describe how many participants met the criteria. The registry records this endpoint in participants, rather than reporting a continuous change in lesion size as the primary outcome.

The assessment schedule was at 12 weeks, then every 8 weeks during treatment, and up to 12 weeks post-treatment if a participant discontinued due to toxicities, subject to a stated maximum of 16 weeks. The timing matters because a response endpoint depends on when and how often participants are assessed. The number classified as responders, the corresponding rate, and any uncertainty interval are not reported in the registry record. The endpoint definition alone cannot establish what response was observed in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome summarized as a count: a participant meets the response definition or does not. The registry specifies that response combines complete response and partial response under RECIST v1.0 criteria. The response definition concerns target lesions assessed by CT. No participant-level response data or primary estimate is reported in the registry record, so an observed response rate or its precision cannot be described from the available information.

What does a confidence interval communicate?

General statistical explanation: a confidence interval is a range of values produced by a method that, over repeated use under its assumptions, has a stated coverage property for the quantity being estimated. For a participant response proportion, an interval would communicate uncertainty around the estimated proportion, rather than identify a set of individual participants or guarantee that the true value lies within that particular interval. No confidence interval for the primary endpoint is reported in the registry record.

What can the single-group design estimate?

The listed design has one treatment group, with no randomized control group. General statistical explanation: a single-group estimate describes outcomes in the observed cohort. A treatment-versus-control contrast requires outcomes under both conditions, and a randomized comparison helps make those groups comparable with respect to measured and unmeasured factors on average. Without a concurrent randomized comparator, differences from an external benchmark would be vulnerable to differences in eligibility, assessment, follow-up, and other features. The registry record does not report an external comparison or an adjusted comparative analysis.

How should a count be read?

A count says how many participants met a stated definition; it is not automatically a rate. A rate or proportion needs an appropriate denominator, and interpretation also depends on who was assessed and how missing assessments were handled. The primary endpoint is recorded as a participant count, but the response count, analysis denominator, and missing-data handling are not reported in the registry record. The enrollment figure alone should not be assumed to be the denominator for the primary endpoint.

What is the role of the assessment schedule?

General statistical explanation: when an outcome is assessed repeatedly, the schedule can affect which events are observed and the timing assigned to them. For this study, the registry states an assessment at 12 weeks, then every 8 weeks during treatment, and follow-up up to 12 weeks after discontinuation due to toxicities, with a maximum of 16 weeks. It does not report whether all planned assessments were completed or how an unassessed participant was classified. The scheduled assessment times describe the intended framework, not the completeness of observed data.

What do planning illustrations mean?

The sample-size planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. These are planning illustrations, not the design of the single-group study described in the registry record. In particular, an assumed two-arm allocation in an illustration should not be mistaken for observed randomization or for the actual study’s treatment allocation. The illustration is based on an observed effect, but the primary response estimate needed to inspect that effect is not reported in the registry record.

General statistical explanation: power is a design-stage probability of detecting a specified effect under a set of assumptions. A planning calculation can show how a hypothetical design might behave under those assumptions, but it does not indicate the probability that the study’s result is true, nor does it measure the probability that a treatment works. It is not observed power. The registry record does not report a sample-size justification for the actual single-group study or enough primary outcome information to evaluate a planning calculation against the observed response.

What can be concluded from the safety counts?

The safety information records participants at risk and affected, as well as a death count and selected serious-event terms. General statistical explanation: a count is most interpretable when the event definition, observation period, denominator, and method of attribution are clear. Comparisons of safety outcomes also require suitable groups and consistent surveillance. The registry record does not provide a randomized safety comparator or detailed information about attribution and overlap among event categories in the reported entries.

Over-dispersion is a general concept in which variability exceeds what a chosen statistical model expects. It can matter when a model’s uncertainty calculations assume less variability than the data contain. The registry information summarized for this endpoint is a binary participant count, and no model for response, variance estimate, or over-dispersion assessment is reported. It would therefore be inappropriate to assert that over-dispersion was present or that a particular model addressed it. More broadly, the registry record does not report the statistical analysis plan, model specification, covariate adjustment, or inferential method for the primary outcome.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Experimental (Endometriod + Serous)", "Exploratory (Uncommon Histology)")
n      <- c(70, 32)
events <- c(9, 2)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Experimental (Endometriod + Serous)  70  9  12.9  6.1  23.0  6.9  22.7  7.0  22.7
ARM  Exploratory (Uncommon Histology)  32  2  6.2  0.8  20.8  1.7  20.1  1.9  20.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists response rate as the primary outcome and includes overall survival and the number of participants with archival specimens that had C-met amplification or mutation as secondary outcomes. It also records four outcome measures, but the available information does not describe how the outcomes were organized into analyses or whether any hypothesis-testing hierarchy was specified. No multiplicity adjustment or strategy for controlling the chance of false-positive findings across multiple tests is reported in the registry record.

Missing-data handling is also not reported in the registry record. In particular, the record does not explain how participants without an evaluable scan, participants who discontinued treatment, or participants with incomplete follow-up were handled for the response endpoint. The assessment schedule is stated, but a schedule does not establish that every participant had an assessment at every planned time.

The analysis population is not described for the primary endpoint. The registry reports enrollment of 102 participants, but it does not state whether the response analysis included every enrolled participant, only participants who received treatment, or a different defined group. The denominator for the response result is not reported. These omissions limit interpretation of any response count because the denominator and rules for classifying unavailable outcomes affect the meaning of a proportion.

Likewise, the record does not report how censoring, follow-up, or missing observations were handled for overall survival. Without these details, the listed secondary outcomes cannot be treated as fully specified analyses. The registry record also does not report interim analyses, stopping rules, or a statistical analysis plan. Their presence or absence should not be inferred.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (5.9%), thromboembolic event (3.9%), diarrhea (3.9%), colonic perforation (3.9%), hyponatremia (2.9%).

The registry records 102 participants at risk for serious adverse events, with 42 recorded as affected. For other adverse events, it records 102 at risk and 102 affected. It also lists 7 deaths. These are counts associated with the treatment group; the registry information does not establish that the treatment caused an event or death. No concurrent control group is listed for a comparative safety assessment.

The listed serious adverse-event terms and percentages are hypertension at 5.9%, thromboembolic event at 3.9%, diarrhea at 3.9%, colonic perforation at 3.9%, hyponatremia at 2.9%, and progressive disease at 2.9%. They describe entries in the registry record, not necessarily a complete account of every event. The record does not explain in this information whether participants could contribute to more than one listed term, how terms were grouped, or how the percentages were derived. These percentages should therefore be read as posted, without converting them to counts or adding them together.

The listed deaths are not accompanied by an attribution statement in the registry information. Event timing, duration, severity grading details beyond the serious-event label, and individual outcomes are not reported. These limitations matter because safety counts depend on definitions and observation. The figures describe what is recorded for this group; they do not support a treatment-versus-control risk comparison.

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

The study record identifies a completed phase 2, single-group investigation of cabozantinib s-malate in recurrent or metastatic endometrial cancer. It specifies a participant-level response endpoint and records selected adverse-event counts. Those details help define the clinical and statistical question, but they do not provide the primary response result. The number of participants meeting complete or partial response criteria and any estimate of response rate are not reported in the registry record.

Consequently, the record does not allow a reader to judge the observed response magnitude or its precision. A response endpoint can be clinically informative, but the definition and schedule alone do not show what happened to participants. Nor does the study’s completed status supply an outcome estimate. The listed overall-survival and archival-specimen outcomes likewise have no numerical results or detailed analyses in the registry information.

The safety entries show recorded affected-participant counts and selected serious-event terms, including 7 deaths. They do not show whether events were caused by treatment, and the single-group design does not provide a randomized basis for comparing risks with another treatment. The reported counts should not be interpreted as proof of harm or proof of safety in isolation.

More broadly, an outcome observed in a single treated cohort does not by itself establish what would have happened to the same participants under a different treatment or under no treatment. General statistical explanation: causal comparisons depend on a credible counterfactual comparison, which random allocation is designed to support. No such control group is described in this registry record. The findings that can be stated are therefore bounded by what is posted: the trial’s design, endpoint definition, schedule, and recorded safety figures. Claims about efficacy, comparative benefit, or causation would go beyond the reported information.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported outcome estimate are both necessary for statistical interpretation. The registry defines response using complete and partial response criteria under RECIST v1.0 and gives an assessment schedule. Those features clarify what would count as response and when it was intended to be evaluated. However, without the response count, denominator, and uncertainty estimate, the primary endpoint cannot be interpreted quantitatively from the registry information.

The single-group design is also statistically important. It allows outcomes to be described in the enrolled cohort, but it does not create a concurrent randomized contrast. That distinction matters whenever readers are tempted to interpret an outcome as evidence of what treatment caused. The design and the registry’s posted results need to be considered together, rather than treating a study title, endpoint definition, or completed status as a treatment-effect estimate.

The safety information provides another useful lesson: counts and percentages need context. Denominators, definitions, overlap among event terms, follow-up, and attribution all affect interpretation. The record lists serious adverse-event and other adverse-event counts and selected serious terms, but does not provide every detail needed to compare risks or establish causation.

Finally, the record shows why planning calculations must be distinguished from study results. The stated sample-size assumptions describe a planning illustration for a two-arm design, while the trial itself is recorded as a single-group study. A planning illustration is not evidence that the trial randomized participants or that its actual design was justified by that calculation. Statistical interpretation depends on matching each number to the question and design it represents.

15. 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.

Important limitations specific to this record include the absence of the primary response count and response estimate. The registry describes the response definition and timing but does not report how many participants met the criteria, the analysis denominator, or an uncertainty interval. Without those items, the primary outcome’s magnitude and precision cannot be assessed.

The single-group design has no concurrent randomized comparator. It can describe outcomes in the treated group but does not provide a direct estimate of how outcomes differ from those under another treatment. The registry also does not report adjusted comparisons or an external control analysis.

The registry does not report the primary analysis population, missing-data rules, protocol deviations, or whether participants completed the planned assessments. These omissions make it difficult to determine how representative any eventual response count would be of the enrolled group. The assessment schedule does not answer these questions.

For safety, counts and selected serious-event percentages are available, but detailed event definitions, attribution, overlap among terms, and event-level timing are not reported in this information. The listed deaths have no stated causal attribution. Because there is no concurrent control group, the figures do not support comparative safety estimates.

The record lists secondary outcomes but does not report their results or analytical methods. It also does not report multiplicity handling, the statistical analysis plan, interim analyses, or the actual study’s sample-size justification. These details should be treated as unreported in the registry record, not assumed to have been handled in a particular way.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cabozantinib S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer — NCT01935934.
• Registry record last updated 2025-10-01; status last verified 2025-09.
• Results first posted 2020-07-14.
• 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.

19. Record Summary

The registry record describes a completed phase 2, single-group study sponsored by the National Cancer Institute, with 102 participants enrolled. Cabozantinib s-malate was given at 60 mg by mouth once daily on days 1-28, with 28-day courses scheduled to repeat absent progression or unacceptable toxicity. The primary endpoint was response rate under RECIST v1.0 criteria, assessed by CT. The study began on 2013-05-08, and primary completion was recorded as 2019-09-12.

The registry lists overall survival and an archival-specimen outcome as secondary outcomes. It records 42 participants affected by serious adverse events among 102 at risk, 102 affected by other adverse events among 102 at risk, and 7 deaths. The primary response result, analysis population, missing-data methods, and detailed statistical analysis plan are not reported in the registry record. With no concurrent control group, the record supports description of the study design and posted counts, not a randomized treatment comparison.