MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma (NCT00853307), a na phase 2 study. The primary outcome is Combined Best Overall Response Rate Based on Investigator Assessment.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group study of alisertib (MLN8237) in platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. The registry record lists an enrollment of 31. It identifies Millennium Pharmaceuticals, Inc. as the sponsor and gives the study status as completed. The listed start date is 2009-03-23, and the primary completion date is 2009-11-23.

The intervention description specifies alisertib 50 mg capsules taken orally twice daily for 7 days, followed by a 14-day washout period in 21-day cycles. Treatment continued until disease progression or unacceptable treatment-related toxicity, with treatment for up to 26 cycles. The registry record does not describe dose adjustments, adherence, or treatment exposure for individual participants.

Allocation is listed as NA, masking as none, and the model as single-group. Accordingly, the record does not describe random assignment or a concurrent control arm. The platinum-refractory and platinum-resistant labels appear in the adverse-event grouping, but this does not make the study a randomized comparison between those groups. Any difference between their recorded outcomes could reflect differences in who entered each group, rather than an effect caused by treatment assignment.

The primary endpoint was a combined best overall response rate based on investigator assessment. Secondary outcomes included progression-free survival, duration of response, time to progression, clinical benefit rate, and counts of participants with treatment-emergent adverse events, serious adverse events, abnormal vital signs, and abnormal laboratory values reported as treatment-emergent adverse events. The registry record does not report a protocol-level statistical plan, a sample-size justification, or interim analyses.

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: Participants with a diagnosis of Platinum-refractory and Platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma received 50 mg alisertib twice daily for 7 days in 21-day cycles.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Response-evaluable population is defined as all participants who have measurable neoplastic disease according to the RECIST criteria OR participants with a CA 125 level \> 40 units/milliliter (mL) and clinical evidence of neoplastic disease and received at least 1 dose of alisertib and have at least 1 post-baseline response assessment.

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: Safety Population is defined as all participants who receive any amount of alisertib.

6. Primary Endpoint

The registry lists the primary outcome as Combined Best Overall Response Rate Based on Investigator Assessment, measured over Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months).

The primary endpoint is the percentage of participants in the response-evaluable population who had a complete response or partial response, assessed by the investigator. The endpoint combines two routes to defining response: RECIST 1.1 assessment and CA 125 response criteria. Under the stated RECIST definitions, complete response means disappearance of all target lesions, while partial response means a 30% decrease in the sum of the longest diameter of target lesions. The CA 125 criteria include either a 50% decrease from 2 initially elevated samples, confirmed by a fourth sample 28 days later, or a serial decrease of > 75% over 3 samples, with the third sample obtained 28 days after the second.

A response rate is a binary-outcome summary: each participant in the analysis population is classified as having or not having a qualifying response, and the endpoint expresses the responding share as a percentage. Using investigator-assessed tumor response and a marker-based criterion can capture response according to the definitions specified in the record. Combining the criteria also means the endpoint is not simply a RECIST-only response rate; interpretation depends on which criterion qualified each participant.

The registry record does not report the response count, the percentage, or the number of participants included in this endpoint analysis. It therefore does not show how often response occurred or how precisely that rate was estimated. The response-evaluable population definition is also truncated in the record after stating that participants received at least 1 dose of alisertib and had at least; the remaining condition is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with identifying what was measured and in whom. The primary outcome is a binary response endpoint expressed as a percentage of participants. A participant either meets the stated complete- or partial-response definition or does not. The primary population is described as response-evaluable, rather than simply all enrolled participants. This distinction is important because eligibility for the analysis can depend on having the required disease measurements or marker information and on receiving treatment.

What does a response percentage represent?

In general, a response percentage is the number of participants classified as responders divided by the number of participants included in the endpoint analysis, expressed as a percentage. The numerator and denominator are both needed to understand the estimate. The denominator indicates how much information contributed to the result, while the numerator indicates how many participants met the endpoint definition. The registry record does not report either number for the primary outcome, so no response percentage can be interpreted from it.

Binary outcomes are often accompanied by a confidence interval. In general, a confidence interval describes the uncertainty around an estimate arising from sampling variability, under the assumptions of the method used. It is not a guarantee that the true value lies within the interval, nor does it remedy limitations in study design, missing information, or population selection. No primary-endpoint confidence interval is reported in the registry record.

Why do the response criteria matter?

The endpoint combines investigator assessment using RECIST 1.1 with CA 125 response criteria. The stated RECIST definitions distinguish complete response, defined as disappearance of all target lesions, from partial response, defined as a 30% decrease in the sum of the longest diameter of target lesions. The CA 125 definition uses specified patterns of decrease across samples, including a 50% decrease from 2 initially elevated samples confirmed by a fourth sample 28 days later, or a serial decrease of > 75% over 3 samples with the third sample obtained 28 days after the second.

These criteria do not measure exactly the same thing: one uses lesion measurements and the other uses a tumor marker over time. Combining them means a qualifying response could be established through either stated route. Interpretation of the overall endpoint would be clearer with counts for each route, but such counts are not reported in the registry record. The record also does not report details about how discordant assessments were handled, how assessments were reviewed, or whether an independent review was used.

What does the single-group structure allow?

A single-group study can describe outcomes among participants who received the intervention. Without a concurrent randomized control group, it does not by itself estimate the difference between treatment and a control condition. General statistical reasoning also cautions that a before-and-after or single-group response observation can be influenced by participant selection, disease course, measurement practices, and other factors. The registry record lists allocation as NA, masking as none, and the model as single-group; it does not report a randomized treatment comparison.

The two platinum-status categories in the adverse-event record should be read as descriptive groupings. They do not constitute randomized arms. Comparisons between such categories may be affected by differences in participant characteristics or clinical status, and the record does not report an analysis designed to adjust for such differences. No causal contrast between the categories is reported.

How should secondary outcomes be viewed?

The registry lists progression-free survival, duration of response, time to progression, and clinical benefit rate among the secondary outcomes, alongside adverse-event and abnormal-measurement counts. Time-to-event outcomes generally describe the time until a specified event, while accounting for participants whose event time is not observed during follow-up requires methods for censoring. In general, censoring occurs when follow-up ends before the event is recorded; interpretation then depends on how follow-up and censoring are handled. The registry record does not provide secondary-outcome estimates, analytic details, or censoring rules.

For adverse events, a count of participants affected is different from a count of event episodes. One participant may experience more than one type of event, and an event can recur; participant counts alone do not convey recurrence or duration. The record presents serious and other adverse-event participant counts by platinum-status group, but it does not report all event-level detail in the registry record for this description.

What is the role of planning calculations?

In general, sample-size planning calculations ask how many participants would be needed under stated assumptions to detect a chosen effect with a specified statistical procedure and power. They are conditional illustrations, not observed outcomes. The registry record does not report that its planning assumptions were the original design assumptions or provide a sample-size justification. A planning calculation based on an observed effect should not be treated as observed power, which is not a substitute for the observed estimate and its uncertainty.

The registry record lists no statistical analyses for the primary outcome. It also does not report the statistical model, adjustment strategy, handling of missing data, confidence-interval method, or hypothesis-testing procedure. Those methods should not be inferred from the endpoint definition alone. In general, the appropriateness of any analysis depends on the outcome, population, follow-up, and assumptions; those details are not fully described in the record.

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("Alisertib 50 mg (Platinum-Refractory)", "Alisertib 50 mg (Platinum-Resistant)")
n      <- c(6, 25)
events <- c(0, 3)
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  Alisertib 50 mg (Platinum-Refractory)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Alisertib 50 mg (Platinum-Resistant)  25  3  12.0  2.5  31.2  4.2  30.0  4.4  30.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary response endpoint, including progression-free survival, duration of response, time to progression, clinical benefit rate, and safety-related counts. When a study examines multiple outcomes or multiple statistical comparisons, the chance of at least one apparently notable result can increase. In general, a prespecified multiplicity strategy may address that issue, but the registry record does not report a plan for multiplicity adjustment or state how the outcomes were prioritized beyond identifying a primary endpoint.

The record lists no statistical analyses for the endpoint. It does not report a statistical analysis plan, planned hypothesis tests, confidence-interval methods, or model specifications. The absence of these details limits assessment of whether analyses followed prespecified methods or how results across outcomes were to be interpreted. It does not establish that no analysis was conducted; it means the analysis information is not reported in the registry record.

The primary population is described as response-evaluable and includes disease measurement or CA 125 conditions, treatment exposure, and an incomplete final eligibility clause. The full definition is not reported in the registry record. The record also does not state how participants with missing response assessments, incomplete marker measurements, or discontinuation before assessment were handled. It does not report whether missing outcomes were excluded, imputed, or treated in another way.

These gaps matter because the analysis population and missing-data approach can affect a binary response estimate. The total enrollment of 31 does not reveal the number included in the primary endpoint analysis, and the response result itself is not reported. The record therefore does not allow a check of the analysis denominator, missingness, or the robustness of any primary result to alternative handling choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stomatitis (16.7%), abdominal pain (16.7%), small intestinal obstruction (16.7%), intestinal obstruction (16.7%), vomiting (16.7%).

The serious adverse-event record divides participants into Alisertib 50 mg (Platinum-Refractory) and Alisertib 50 mg (Platinum-Resistant). In the platinum-refractory group, 6 participants were at risk and 4 were affected by serious adverse events. In the platinum-resistant group, 25 participants were at risk and 7 were affected. These are counts of participants affected, not counts of all serious-event episodes. The record also lists other adverse events for 6 of 6 participants in the platinum-refractory group and 24 of 25 in the platinum-resistant group.

The listed serious-event terms are stomatitis, abdominal pain, small intestinal obstruction, intestinal obstruction, vomiting, and neutropenia, each shown with 16.7%. The registry record does not provide enough detail in this listing to assign those term percentages to a specific group or to determine whether participants experienced more than one listed term. These percentages should not be treated as a complete account of event frequency or severity.

The groups are not randomized comparison arms, and the figures do not establish that one group had a safer or less safe experience. Death counts are not reported in the registry record. The record also does not provide event timing, duration, recurrence, or a full account of attribution to treatment. These safety figures are descriptive and should be read with those limitations.

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

The registry record establishes that this was a phase 2, single-group study of alisertib in participants with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. It specifies the treatment schedule and describes a combined investigator-assessed response endpoint using RECIST 1.1 or CA 125 criteria. It also lists secondary efficacy and safety outcomes and provides selected adverse-event counts.

Those details explain what the study set out to measure and the general setting in which outcomes were collected. They do not establish the observed response rate. The primary endpoint result, analysis denominator, and uncertainty estimate are not reported in the registry record. The absence of that result cannot be read as a response rate of zero, nor can it be interpreted as evidence that responses did or did not occur.

The study structure also limits what can be inferred. A single-group design does not provide a randomized concurrent control for estimating a treatment contrast. The platinum-refractory and platinum-resistant categories in the adverse-event listing are not treatment-versus-control groups. Any descriptive outcome in a treated group would not, by itself, identify what would have happened under a different treatment or no treatment.

The adverse-event counts describe participants affected, rather than all episodes, and the listed term percentages do not supply a complete safety analysis. The registry record does not report the primary response analysis methods, missing-data handling, or a full statistical plan. As a result, the record supports a description of the study design and endpoint definitions, but not a conclusion about the size, precision, or comparative meaning of the primary response outcome.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and endpoint results must be considered separately. The registry record describes an investigator-assessed combined response endpoint in detail, including lesion-based RECIST criteria and CA 125 criteria. Yet the primary response value and the number of participants analyzed are not reported. A detailed definition is useful for understanding what would count as a response, but it cannot substitute for the observed estimate or its uncertainty.

It also highlights the importance of study design when interpreting outcomes. This is a single-group study with allocation listed as NA and masking as none. The platinum-status categories in the adverse-event record do not create a randomized comparison. Statistical descriptions of outcomes in treated participants answer a different question from a controlled estimate of the difference between treatment strategies.

The record further shows why analysis populations matter. Enrollment is reported as 31, while the primary outcome is defined for a response-evaluable population with eligibility conditions tied to disease assessment or CA 125 and treatment exposure. The endpoint population wording is incomplete, and its denominator is not reported. Without a complete population definition and analysis count, readers cannot determine how much of the enrolled group contributed to the primary endpoint.

Finally, multiple secondary outcomes and safety measures are listed, but no statistical analysis plan or multiplicity approach is reported. These omissions do not prove that methods were absent; they limit what can be evaluated from the registry record. The study is statistically informative as an example of the questions readers should ask about estimands, denominators, uncertainty, control groups, and missing data before drawing conclusions from a trial record.

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 most consequential limitation for interpreting efficacy is that the primary response result is not reported in the registry record. The response count, percentage, analysis denominator, and uncertainty estimate are all absent. The record therefore does not permit an assessment of the observed response rate or its precision.

The response-evaluable population definition is incomplete: it states that participants received at least 1 dose of alisertib and have at least, but does not include the remainder of the criterion. The record does not report how many enrolled participants met the complete endpoint definition or how participants with missing assessments were handled. This prevents a clear reconciliation between enrollment and the primary analysis population.

The single-group, unmasked design provides no randomized control comparison. The platinum-refractory and platinum-resistant labels are descriptive groups in the adverse-event record, not randomized treatment assignments. The registry record does not report methods for adjusting comparisons between those categories or details that would support a causal interpretation.

The record also does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity strategy, or detailed methods for secondary outcomes. The listed safety counts omit event-level information such as timing and recurrence, and death counts are not reported in the registry record. These limitations concern what can be evaluated from the registry record; they should not be mistaken for evidence that an unreported procedure or outcome did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma — NCT00853307.
• Registry record last updated 2022-04-08; status last verified 2022-04.
• Results first posted 2018-03-27.
• 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

NCT00853307 is a completed phase 2, single-group study of alisertib (MLN8237) in platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Enrollment was 31. The listed regimen was alisertib 50 mg orally twice daily for 7 days, followed by a 14-day washout in 21-day cycles, for up to 26 cycles.

The primary endpoint was combined best overall response rate based on investigator assessment using RECIST 1.1 or CA 125 criteria. The registry record does not report the primary endpoint result, its denominator, or an uncertainty estimate. It lists secondary efficacy and safety outcomes and selected adverse-event participant counts by platinum-status group. The record does not provide a complete statistical analysis plan or a complete response-evaluable population definition.