Alisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Alisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus (NCT01637961), a na phase 2 study. The primary outcome is Progression-free Survival (PFS) > 6 Months.

2. Clinical Question

3. Trial Design

This is a phase II, single-group study of alisertib in patients with recurrent or persistent leiomyosarcoma of the uterus. The registry record lists 23 participants as enrolled. It records the study as completed, with a start in 2012-08 and primary completion in 2014-08. These dates describe the record; they do not establish when every participant entered, finished treatment, or had follow-up.

Participants in the treatment group received alisertib by mouth twice daily on days 1–7. Courses were scheduled to repeat every 21 days while there was no disease progression or unacceptable toxicity. Laboratory biomarker analysis is also listed. The registry records no masking and no allocation scheme; the trial model is single group.

The primary outcome is the percentage of eligible and treated participants who remained progression-free for at least 6 months. Secondary outcomes listed include overall survival, participants with adverse events assessed using NCI CTCAE Version 4.0, and progression-free survival. The record lists six outcome measures in total, but the detailed information available does not give results for those measures.

There is no concurrent comparator arm. Consequently, the study describes outcomes in the treated group rather than an estimate of the difference between alisertib and another treatment or a control condition. The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or details of treatment adherence.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible and Treated Patients

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: Eligible and treated patients.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS) > 6 Months, measured over Assessed every other cycle for the first 6 months; then every 3 months from the date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months..

The primary endpoint asks whether a participant survived without progression for at least 6 months, and reports the result as a percentage of participants. This is a binary endpoint: each participant is classified according to whether the stated time-based condition was met. It combines the timing of progression with survival during that period, rather than measuring a tumor measurement alone.

The registry describes assessment every other cycle for the first 6 months, then every 3 months from enrollment until first documented progression or death from any cause, whichever came first. Follow-up was planned to extend up to 60 months. Progression is defined using imaging criteria: at least a 20% increase in the sum of target-lesion diameters relative to the smallest sum on study, with an absolute increase of at least 5 mm. New lesions and unequivocal progression of existing non-target lesions are also included in the definition.

As a general statistical point, a fixed-time progression-free endpoint can make a clinically interpretable summary of the proportion meeting a specified disease-control duration. It does not, by itself, describe the full pattern of event times or the length of progression-free time beyond the threshold. A confidence interval is useful because the observed percentage from a study is an estimate, with uncertainty that depends in part on the number of participants and their outcomes. The registry record states that a 90% Bonferroni-corrected confidence interval was intended, but does not report the endpoint estimate or interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary percentage describe?

The primary outcome is recorded as a percentage of participants meeting a yes-or-no condition: remaining progression-free for at least 6 months. In general, such an estimate depends on the number classified as meeting the condition and the number evaluated. A percentage can be easy to interpret, but it compresses individual follow-up into a single threshold-based summary. It does not show when each progression or death occurred, nor how far beyond the threshold participants remained progression-free.

The registry record does not give the observed percentage or the numbers used to calculate it. It also does not describe how participants whose progression status was unknown at the threshold were classified. Consequently, the endpoint cannot be reconstructed from the record details available for this analysis.

What is the role of a confidence interval?

In general, a confidence interval provides a range of values compatible with the observed estimate under a specified statistical procedure. It communicates estimation uncertainty, rather than proving that the true value lies within a particular range for an individual study. Its width is affected by the amount of information in the data and by the method used to calculate it.

The endpoint description specifies a 90% confidence interval and says that it is Bonferroni corrected. This identifies an adjustment, but the record does not state the correction’s scope or give the interval limits. A correction for multiplicity is intended, in general, to account for making more than one statistical assessment, so that the overall chance of false-positive findings is controlled under a stated framework. The exact family of comparisons or endpoints covered by this correction is not reported in the registry record.

Why does the endpoint definition matter?

The endpoint uses an explicit definition of progression. Target-lesion progression requires at least a 20% increase in the sum of diameters from the smallest sum recorded on study, and an absolute increase of at least 5 mm. The description also counts one or more new lesions and unequivocal progression of existing non-target lesions. It cautions that non-target progression should represent overall disease-status change and should not normally override target-lesion status on the basis of a single lesion increase.

As a general matter, prespecified definitions help make outcome classification more consistent. They also determine which events count and when an endpoint is reached. The registry specifies assessment every other cycle for the first 6 months, then every 3 months from enrollment until progression or death, with follow-up up to 60 months. It does not report the actual assessment schedule achieved for participants or how missed assessments were handled.

What can the study design estimate?

This is a single-group study with no comparator. In general, a single-group study can report the proportion of participants meeting an endpoint and describe observed outcomes, but it cannot estimate a randomized difference between treatment and control. Other factors can contribute to observed outcomes, and a single-group result does not separate those influences from the effect of treatment.

The registry record reports no analyses, and the primary outcome estimate is not reported in the registry record. It also does not report whether the endpoint analysis used a particular inferential test, how missing observations were treated, or whether any covariate adjustment was planned. The stated 90% Bonferroni-corrected interval is the only specific inferential method described for this primary outcome.

How should planning calculations be distinguished from observed results?

As a general statistical principle, sample-size planning calculations describe hypothetical design requirements under stated assumptions; they are not observed participant outcomes and are not evidence of the precision actually achieved. The registry record does not report a sample-size justification for the trial. Any planning illustration should therefore be kept distinct from the trial’s observed outcome data, which are not reported for the primary endpoint.

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("MLN8237")
n      <- c(21)
events <- c(0)
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  MLN8237  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description specifies a 90% Bonferroni-corrected confidence interval. The registry record does not state which outcomes or comparisons were included in the correction, or how the family of statistical assessments was defined. Six outcome measures are listed, including the primary endpoint and secondary outcomes such as overall survival, adverse events, and progression-free survival. The record lists no analyses. It does not report a broader multiplicity strategy or results from individual outcome analyses.

The endpoint population is described as eligible and treated patients, but the record does not provide the analysis denominator or explain how eligibility and treatment status were applied. It does not report how missing assessments, withdrawal, progression before the six-month threshold, or other incomplete follow-up were handled. These omissions prevent an assessment of whether missing outcome information could affect the reported percentage; in fact, the percentage itself is not reported in the registry record.

As a general statistical matter, missing data can alter an endpoint estimate when the participants with observed outcomes differ from those without them. The direction and size of any effect depend on the missingness pattern and the analysis rules, so they cannot be inferred from the fact of missingness alone. The registry record does not describe imputation, censoring, sensitivity analyses, or alternative analysis populations.

The safety entry identifies 21 participants at risk, but this should not be treated as the primary endpoint denominator. No analysis population beyond the primary endpoint’s eligible-and-treated description is reported in the registry record.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (4.8%), febrile neutropenia (4.8%), sinus tachycardia (4.8%), vaginal hemorrhage (4.8%), palmar-plantar erythrodysesthesia syndrome (4.8%).

The registry record lists 21 participants at risk for serious adverse events in the MLN8237 group, with 5 recorded as affected. The listed serious adverse-event terms are anemia, febrile neutropenia, sinus tachycardia, vaginal hemorrhage, and palmar-plantar erythrodysesthesia syndrome; each is reported as 4.8%. The record also lists 21 participants at risk and 21 affected for other adverse events. These are safety counts, not measures of treatment benefit.

As a general statistical point, a count of affected participants is different from a count of event episodes: one participant may experience more than one event. The registry entry does not explain whether the displayed serious-event terms represent unique participants or event reports, or whether participants could appear under multiple terms. The deaths field is not reported in the registry record.

Adverse events are listed as assessed using NCI CTCAE Version 4.0. The record does not provide the full event listing, severity distribution, timing, duration, or attribution details. These figures should therefore be read as the adverse-event information recorded for this group, not as a complete characterization of safety or as a comparison with another treatment.

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

The record describes a phase II study of alisertib in a single group of participants with recurrent or persistent uterine leiomyosarcoma. It defines a primary endpoint based on remaining progression-free for at least 6 months and identifies a 90% Bonferroni-corrected confidence interval. However, the registry record does not report the primary endpoint percentage, its confidence interval, or the number of participants included in that analysis. The central outcome therefore cannot be interpreted from the information available.

Even if a single-group outcome estimate were reported, it would describe what happened in that group rather than establish what would have happened under a comparator condition. There is no control group in this study record, so it cannot provide a like-for-like treatment comparison or a randomized estimate of a treatment effect. No conclusion that alisertib does or does not work follows from the design description or the missing endpoint result.

The enrollment of 23 gives context for the scale of the study, but it does not reveal the endpoint denominator, the amount of follow-up available, or the precision of the primary estimate. Likewise, the serious adverse-event counts describe recorded safety information but do not establish a comparative safety profile. The registry record does not report a complete analysis plan, missing-data approach, or results for the other listed outcomes.

As a general principle, estimates should be interpreted alongside their uncertainty, analysis population, outcome definition, and study design. Here, the endpoint definition is detailed, but the numerical result and important analysis details are absent from the registry record. The appropriate statistical reading is therefore limited to describing the study’s design and stated measurement approach, while recognizing that its primary outcome result is not reported.

14. Why This Trial Matters Statistically

This study illustrates why an outcome definition and an outcome estimate are both needed for statistical interpretation. The registry gives a detailed rule for progression and specifies a fixed progression-free threshold, along with the intended confidence-interval type. Yet without the observed percentage, interval limits, and analysis denominator, readers cannot judge the magnitude or precision of the result. A carefully stated endpoint does not replace reporting the data used to estimate it.

The single-group design is also central to interpretation. It allows outcomes in the treatment group to be described, but does not supply a concurrent control for estimating a treatment contrast. This distinction is important when reading an apparent outcome as evidence: a within-group result and a between-group comparison answer different statistical questions.

The entry also highlights the need to distinguish enrollment from analysis populations and safety populations. The record lists 23 enrolled participants, while the safety information uses 21 at risk. The primary endpoint population is described as eligible and treated, but its denominator is not reported. Such population details are necessary for understanding what a percentage represents and how it relates to the study’s enrolled participants.

Finally, the registry notes a Bonferroni-corrected confidence interval but does not explain its scope. Statistical adjustment is interpretable only in the context of the analyses it is intended to cover. Together, these features make the record useful for understanding the planned clinical question and its measurement, while underscoring the limits imposed by unreported outcomes and analysis details.

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.

The principal limitation for statistical interpretation is that the registry record does not report the primary endpoint estimate or its confidence interval. It also does not report the number of participants included in the endpoint analysis. The enrollment count alone cannot fill those gaps, and the difference between enrollment and the safety at-risk count does not identify which participants contributed to the primary outcome.

The study has no comparator group, so it cannot estimate a randomized contrast. The record lists no masking, and it does not describe additional safeguards for outcome assessment. It gives progression criteria and an assessment schedule, but does not report how assessments were completed in practice, how missing or delayed assessments were handled, or whether endpoint classification was independently reviewed.

The record does not report a sample-size justification, interim analyses, or the full statistical analysis plan. It identifies a Bonferroni-corrected interval without stating the family of outcomes or comparisons covered. Missing-data methods and alternative analysis populations are also not reported. These details matter because analysis choices and incomplete outcome information can affect both estimates and their interpretation.

The safety information is limited to the listed at-risk and affected counts and selected serious-event terms. The deaths entry is not reported in the registry record, and details such as event timing, duration, severity distribution, and attribution are not included in the registry entries. These limitations restrict conclusions about both the primary outcome and the broader clinical profile of the study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Alisertib in Treating Patients With Recurrent or Persistent Leiomyosarcoma of the Uterus — NCT01637961.
• Registry record last updated 2019-07-23; status last verified 2019-07.
• Results first posted 2015-07-17.
• 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

NCT01637961 is a completed phase II, single-group trial of alisertib in recurrent or persistent leiomyosarcoma of the uterus. The registry lists 23 participants enrolled, a study start in 2012-08, and primary completion in 2014-08. Participants received alisertib by mouth twice daily on days 1–7, with courses repeating every 21 days in the absence of progression or unacceptable toxicity.

The primary outcome is the percentage of eligible and treated participants progression-free for at least 6 months, with a 90% Bonferroni-corrected confidence interval specified. The primary result and its analysis denominator are not reported in the registry record. There is no comparator group. Secondary outcomes include overall survival, adverse events, and progression-free survival. Safety information lists 21 participants at risk and 5 affected for serious adverse events, and 21 at risk and 21 affected for other adverse events.