VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer (NCT00462826), a na phase 2 study. The primary outcome is Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0.

2. Clinical Question

The registry record describes a phase II study of VEGF Trap, also called aflibercept, in patients with recurrent or persistent endometrial cancer. Its primary question concerns safety: how many eligible and evaluable patients experienced adverse events considered at least possibly related to the study agent, as assessed using Common Terminology Criteria for Adverse Events version 3.0. The record also lists duration of progression-free survival and duration of overall survival as secondary outcomes.

The study description also gives a biological rationale: VEGF Trap may act by blocking blood flow to a tumor and by carrying tumor-killing substances to cancer cells. That rationale is not itself a measured endpoint. The record does not report results for the primary endpoint or for the listed progression-free and overall survival outcomes. Consequently, the registry entry describes the questions and treatment schedule, but does not establish an observed treatment effect or permit a comparison with another treatment.

3. Trial Design

NCT00462826 is recorded as a completed phase II study sponsored by the National Cancer Institute. The registry lists a single-group model, allocation as not applicable, and no masking. Enrollment is recorded as 49. The study began in 2007-11, and primary completion is recorded as 2013-01. These are registry entries; they do not by themselves describe the number of patients who received treatment or contributed data to each outcome.

Patients in the treatment group received aflibercept intravenously over 1 hour on days 1 and 15. The schedule repeated every 28 days while disease had not progressed and unacceptable toxicity had not occurred. The registry does not give additional details about dose, treatment duration, dose modifications, or reasons for stopping beyond those conditions.

A single-group design describes outcomes among participants receiving the study treatment, without a concurrent control group. It can document what happened in the group, but it does not provide a like-for-like estimate of how outcomes would have differed under another treatment or under no study treatment. The record explicitly identifies the study as not a randomized comparison. No causal conclusion should be drawn from an uncontrolled group result alone.

The primary endpoint is a participant count for adverse events at least possibly related to the study agent, assessed using CTCAE version 3.0. The assessment timeframe is every cycle while on treatment and 30 days after the last cycle. The primary endpoint population is described as eligible and evaluable patients. The registry separately lists duration of progression-free survival and duration of overall survival as secondary outcomes, but does not report their results or analysis details.

The record lists five outcome measures and zero analyses. It does not report a statistical analysis plan, planned sample-size justification, interim analyses, or methods for handling missing outcome data. The completed status indicates the registry record's status designation; it does not supply results that are absent from the posted record.

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: Patients were required to have had one prior chemotherapeutic regimen for the treatment of endometrial carcinoma. Patients entering the study therefore were required to have either persistent or recurrent cancer that was measurable by RECIST.

Overall Study

Reasons for not completing this period:

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: Number of Eligible and Evaluable Participants

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Incidence of Adverse Events at Least Possibly Related to Study Agent as Assessed by Common Terminology Criteria for Adverse Events Version 3.0, measured over Assessed every cycle while on treatment, 30 days after the last cycle of treatment.

The primary endpoint counts participants who experienced adverse events judged at least possibly related to the study agent. The registry specifies CTCAE version 3.0 as the assessment standard and names eligible and evaluable patients as the endpoint population. Assessments were scheduled every cycle during treatment and 30 days after the last cycle of treatment.

A participant count is a direct way to describe how many people in the defined population experienced an event meeting the endpoint definition. It is useful for summarizing safety observations, while the attribution threshold makes clear that the endpoint is limited to events considered at least possibly related to the agent. It is not a count of every symptom or event regardless of attribution, and it is not a measure of tumor response.

In general, endpoint interpretation depends on the population and observation period as well as the event definition. The stated follow-up window matters because events occurring outside that window may not be captured by this endpoint. Likewise, the eligible-and-evaluable population is not automatically identical to all enrolled patients. The registry does not give the primary endpoint result, event-level detail for this endpoint, or the number included in its eligible-and-evaluable population. Therefore, the endpoint's definition can be described, but its observed frequency cannot be assessed from the posted record.

Progression-free survival and overall survival are listed separately as secondary outcomes. The record does not report their outcome values, definitions of events, or analysis methods. They should not be treated as findings of the primary adverse-event endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies a participant-count primary endpoint and a single-group design. It does not report the analysis procedures used to produce the posted results. The concepts below explain how such information is generally interpreted; they are not claims about methods used in this trial unless explicitly stated in the record.

What does a participant count represent?

For a binary event outcome, each participant is classified according to whether the event definition was met during the stated observation period. A count describes the number who met that definition; interpretation also requires a clearly defined denominator and population. Here, the primary endpoint is the number of eligible and evaluable patients with an adverse event at least possibly related to the agent, assessed under CTCAE version 3.0. The registry does not report the endpoint count or its denominator, so a primary endpoint frequency cannot be reconstructed from the record.

The serious and other adverse-event summaries are separate safety fields. Each reports 44 at risk, with 24 and 28 affected participants, respectively. The record does not explain whether participants could appear in both categories, and the counts should not be added together. Nor should they be substituted for the primary endpoint: the endpoint concerns adverse events at least possibly related to the study agent, whereas the separate summaries are described as serious and other adverse events.

Why does a single-group design matter?

A single-group study observes outcomes in a treated group without an untreated or active-comparator group. In general, a proportion or count in that group is descriptive. It cannot by itself estimate the contrast between treatment strategies because there is no concurrently observed control outcome. Differences from historical experience, if any, would be vulnerable to differences in eligibility, follow-up, supportive care, event ascertainment, and other factors. The registry does not present a randomized comparison.

Masking is recorded as none. In general, masking can reduce the influence of knowledge of treatment assignment on some aspects of assessment or reporting. In an unmasked study, such influence can be a consideration, particularly when outcomes depend on judgment. The record does not describe procedures for independent event review or other safeguards, so these should not be assumed.

What can a confidence interval tell a reader?

In general, a confidence interval expresses statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. It does not correct for bias or create a comparator that a single-group study does not have. The registry record does not report a confidence interval for the primary endpoint or the listed secondary outcomes.

For participant counts, uncertainty is commonly considered in relation to an estimated event frequency, which requires both an event count and an appropriate denominator. Neither a primary endpoint estimate nor its denominator is posted. No interval should therefore be inferred from the separate adverse-event summaries.

What is over-dispersion, and is it relevant?

In general, over-dispersion means that observed variability is greater than expected under a particular statistical model. It can affect standard errors and confidence intervals when a model assumes less variability than the data contain. The primary outcome described in this record is a participant count, not a reported rate model, and no model specification or over-dispersion assessment is reported. It would be inappropriate to claim that over-dispersion was tested or corrected in this study.

What do the planning assumptions mean?

The record includes a sample-size-planning description based on an observed effect, a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect; time-to-event planning uses a total event count, while other planning values refer to participants per arm. These are planning illustrations, not observed power and not evidence that the study itself was designed using those assumptions. The registry does not report the trial's own sample-size justification. No planning result should be interpreted as a trial outcome.

In general, a planning calculation depends on assumptions about the target effect, variability or event frequency, allocation, significance level, and desired power. Changing an assumed effect can change the resulting planned sample size. A planning illustration based on an observed effect is especially dependent on the stability and relevance of that estimate. The record does not report the numerical planning outputs in the registry record for this analysis, so none can be stated.

What analyses are actually reported?

The registry lists zero analyses. It does not report a statistical analysis plan, an analysis population beyond the endpoint's description as eligible and evaluable patients, methods for missing data, adjustment for multiple outcomes, or interim analyses. General explanations of these methods cannot fill in trial-specific details. The absence of those details limits assessment of how outcome estimates would have been selected, calculated, or interpreted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary adverse-event endpoint and the secondary outcomes of duration of progression-free survival and duration of overall survival. It lists zero analyses. The posted record does not report whether the study used a prespecified hierarchy, adjusted significance thresholds, or another method to address testing multiple outcomes. A multiplicity adjustment should not be assumed.

In general, when several outcomes or statistical comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed without accounting for the number of tests. A prespecified testing strategy can help clarify which outcomes are confirmatory and how results should be interpreted. Here, the record identifies one primary endpoint and secondary outcomes, but the statistical handling of that set is not reported in the registry record.

The record does not report a missing-data strategy, reasons for missing measurements, or how incomplete follow-up was handled. In general, missing outcomes can affect interpretation when the likelihood of being observed is related to a participant's health or outcome. Different assumptions about missing information can lead to different estimates. No such assumptions or sensitivity analyses are described.

The primary endpoint population is stated as eligible and evaluable patients, but the record does not define the evaluability criteria or give the number in that population. Enrollment is listed as 49. Separately, safety summaries report 44 at risk. These figures should not be conflated, and the record does not state whether the at-risk group corresponds to the primary endpoint population. An intention-to-treat population is not reported in the registry record.

The record also does not report interim analyses, stopping rules, or adjustments associated with any interim monitoring. Their presence or absence should not be inferred from the completion status. These omissions make it difficult to assess the full analysis process, but do not change the design information and safety counts that are explicitly recorded.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: death no ctcae term - disease progression nos (6.8%), hypertension (4.5%), neutrophils (2.3%), lt ventricular systolic dysfunction (2.3%), fever (2.3%).

The registry's serious-adverse-event summary reports 24 affected participants among 44 at risk. Its separate other-adverse-event summary reports 28 affected participants among 44 at risk. The record does not explain the relationship between these categories, so the counts should not be added or treated as mutually exclusive. They also should not be equated with the primary endpoint, which counts eligible and evaluable participants with events at least possibly related to the study agent.

Among the listed serious-event terms, the record gives “Death No Ctcae Term - Disease Progression Nos” as 6.8%, hypertension as 4.5%, and neutrophils, left ventricular systolic dysfunction, fever, and colon gastrointestinal perforation as 2.3% each. The registry record does not provide the denominator or further calculation details for these term-level percentages. The listed death-related term is not a reported death count; the death count is not reported in the registry record.

These figures are descriptive. Without a concurrent comparator group, they do not establish whether event frequency differs from another treatment or from the course of the disease. The record does not provide detail on individual event timing, duration, recurrence, or overlap. These summaries therefore offer a limited account of the recorded safety categories, not a complete characterization of risk.

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

The record establishes that a phase II, single-group study of aflibercept in recurrent or persistent endometrial cancer was completed. It describes the treatment schedule and a primary safety question based on adverse events at least possibly related to the study agent. It also records serious and other adverse-event counts and several serious-event terms with percentages.

Those details do not establish how often the primary endpoint occurred, because its result and denominator are not reported. The separate safety summaries do show 24 affected participants among 44 at risk for serious adverse events and 28 among 44 at risk for other adverse events. These descriptions should be read within their own categories and should not be merged into a single count. The listed term-level percentages also lack the denominator and further calculation details in the registry record.

The study's single-group design means the posted information does not show what would have happened to a comparable group receiving another treatment or no study agent. Consequently, the record cannot establish a treatment difference or attribute all observed events to aflibercept. The primary endpoint's “at least possibly related” criterion is a safety attribution definition, not a controlled causal comparison.

Although progression-free survival and overall survival appear as secondary outcomes, their results are not reported. The record therefore does not support conclusions about tumor control or survival. It also does not report confidence intervals or statistical analyses that would show the precision of an outcome estimate. A study's completed status and enrollment figure do not substitute for outcome results.

In general, a registry entry is most informative when interpreted according to its design, outcome definitions, analyzed populations, and available uncertainty estimates. In this case, the defensible interpretation is limited to the design and the posted descriptive safety information. The absence of reported outcome analyses is not evidence that an outcome did or did not occur, and it should not be treated as evidence for or against treatment benefit.

13. Why This Trial Matters Statistically

This study illustrates why statistical interpretation starts with the design and endpoint rather than with a treatment claim. A single-group phase II study can document treatment exposure and observed safety events, but it lacks a concurrent comparator for estimating a treatment contrast. That distinction remains important even when a registry identifies a completed study and lists a substantial enrollment figure.

The primary endpoint is also specific: it counts eligible and evaluable participants whose adverse events were considered at least possibly related to the study agent. That is not the same as counting all adverse events, all serious adverse events, or measuring efficacy. Separating this endpoint from the registry's serious and other adverse-event summaries avoids combining outcomes with different definitions.

The record demonstrates the importance of denominators and analysis populations. It reports enrollment of 49, while separate safety summaries report 44 at risk. The record does not explain the relationship between them, and it does not give the primary endpoint denominator. Without those details, even a clearly stated endpoint cannot be fully quantified from the posted information.

Finally, the record lists progression-free and overall survival outcomes but does not report their analyses. A named outcome is not an outcome finding. Likewise, planning assumptions are not observed power or evidence of a result. Keeping these distinctions clear helps readers separate the study's stated aims, its recorded safety summaries, and the conclusions that the available information can support.

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 trial-specific limitation is the single-group design. There is no randomized or other concurrent comparator in the registry record, so observed outcomes cannot be interpreted as comparative effects. The record lists no masking. It does not describe independent outcome review or other procedures that might address the influence of unmasked assessment.

The primary endpoint result is not reported, and the eligible-and-evaluable denominator is not given. Although enrollment is listed as 49, the safety summaries separately report 44 at risk. The registry does not explain this difference or establish that these populations are the same. The serious and other adverse-event counts may not represent separate groups of participants, and no overlap information is reported.

Outcome reporting is incomplete for interpretation of efficacy. Progression-free survival and overall survival are listed as secondary outcomes, but their results, event definitions, follow-up information, and analysis methods are not reported. The record lists zero analyses and does not provide confidence intervals for the primary or secondary outcomes.

The record also does not report a statistical analysis plan, missing-data methods, the handling of multiple outcomes, interim analyses, or the study's own sample-size justification. The term-level serious-event percentages are not accompanied by a stated denominator or calculation details in the posted information. The death count is not reported in the registry record. These gaps limit assessment of precision, completeness, and the analysis process, and they preclude stronger conclusions than descriptive reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: VEGF Trap in Treating Patients With Recurrent or Persistent Endometrial Cancer — NCT00462826.
• Registry record last updated 2019-07-23; status last verified 2019-07.
• Results first posted 2013-09-16.
• 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

NCT00462826 is a completed phase II, single-group study sponsored by the National Cancer Institute. It enrolled 49 participants with recurrent or persistent endometrial cancer and evaluated ziv-aflibercept. The registry records no masking and allocation as not applicable.

The primary endpoint was the number of eligible and evaluable participants with adverse events at least possibly related to the study agent, assessed using CTCAE version 3.0. The record lists progression-free survival and overall survival as secondary outcomes. It does not report results for these outcomes or the primary endpoint, and it lists zero analyses.

Safety summaries report 24 affected participants among 44 at risk for serious adverse events and 28 among 44 at risk for other adverse events. Several serious-event terms are listed with percentages, but further denominator details are not reported. The single-group design and incomplete outcome reporting limit interpretation to the registry's descriptive information.