ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer (NCT03485729), a non-randomized phase 2 study. The primary outcome is Progression-Free Survival Rate at 2 Months.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase II study, with non-randomized allocation, no masking, and a parallel model. The brief summary describes an open-label, 2-arm study and calls the design a Simon two-stage trial. However, the intervention descriptions list Arm A, Arm B, and Arm C, with different dosing or biopsy requirements. The registry record does not explain this difference in how the arms are described, or report how participants were assigned among them.

The overall enrollment is 27. The study began on 2018-03-21, had a primary completion date of 2023-01-19, and is listed as terminated. The reason for termination and the timing of the termination are not reported in the registry record. The brief summary says the study was completed by predecessor company Oncoceutics, Inc.; the listed sponsor is Jazz Pharmaceuticals.

Arms A and B used 625 mg dordaviprone once weekly on Days 1, 8, and 15 of each 3-week cycle. Arm A required a tumor biopsy one day after the second dose in Cycle 1, while Arm B did not require a biopsy. Arm C used 625 mg twice weekly on consecutive days on Days 1, 2, 8, 9, 15, and 16 of each 3-week cycle, with a biopsy one day after the fourth dose in Cycle 1. The registry record does not explain the rationale for these arm differences or provide arm-specific enrollment totals in the trial description.

The primary endpoint was designated for Arm B only. The registry states that the biopsy requirement in Arms A and C, and its absence in Arm B, informed this restriction. The endpoint analysis population and the number of Arm B participants contributing outcome data are not reported in the registry record. No results for the primary endpoint are posted among the recorded 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Note that only Arm B participants were planned to be assessed for progression-free survival at 2 months following treatment initiation. Participants in Arm A and Arm C were required to undergo a biopsy of their tumor during the study; participants in Arm B were not. Therefore, including participants in Arm A and Arm C may have represented a biased subset of the overall target population since some sites of metastases may not have been amenable to biopsy.

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 Progression-Free Survival Rate at 2 Months, measured over 2 months (8 weeks); from treatment initiation to 2 months (8 weeks) following treatment initiation.

Progression-free survival rate at 2 months is a fixed-time measure: it asks what proportion of a specified group remained progression-free through a stated time after treatment began. The registry defines the endpoint as the percentage of participants with progression-free survival for >8 weeks (>56 days) following treatment initiation. It describes the timeframe as 2 months (8 weeks) from treatment initiation to 2 months (8 weeks) after treatment initiation.

As a general statistical concept, a fixed-time rate can give readers a direct description of the share of an analysis group meeting an event-free status at a clinically specified point. It is not the same as reporting each participant’s follow-up duration or a full time-to-event curve. Interpretation depends on the endpoint definition, the analysis population, the way progression and follow-up are assessed, and how participants without complete follow-up are handled.

In this study, only Arm B participants were analyzed for the endpoint. The registry explains that Arm A and Arm C participants were required to undergo a tumor biopsy during the study, whereas Arm B participants were not. The result itself is not reported in the registry record: no endpoint count, rate, or confidence interval is listed. The assessment criteria for progression and the handling of missing or censored follow-up are also not reported in the registry record. Without those details and the numerical result, the endpoint’s observed value and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a Phase II, non-randomized, open-label, parallel study. These terms describe how treatment groups were organized and how the study was conducted; they do not supply an estimate of treatment effect. Non-randomized allocation means the record does not establish that participants were assigned to the listed arms by chance. Open-label means the study was not masked. In general, random assignment can help balance known and unknown prognostic characteristics across groups, while masking can reduce some risks of biased assessment or behavior. Neither feature is present in the listed design, and the registry record does not report other methods used to address these concerns.

The brief summary calls the study a Simon two-stage trial. In general, a Simon two-stage design is a framework for making a decision about continuing a single-arm study after an interim stage, based on a specified outcome and decision rules. The registry record does not report the design thresholds, stage-specific enrollment targets, stopping boundaries, or whether a formal interim analysis was conducted. Those details cannot be inferred from the design label alone. The presence of a Simon two-stage label does not establish what decision rules were used or how the study’s eventual termination relates to them.

The primary outcome is a binary status at a fixed time: participants either met the stated progression-free definition or did not, as determined by the study’s endpoint rules. A rate summarizes the proportion meeting that definition in the relevant analysis group. A confidence interval, if reported, would express statistical uncertainty around the estimate under the assumptions of the analysis; it would not guarantee that the true rate lies within that particular interval. The registry does not post the outcome count, rate, or confidence interval, so no numerical estimate or precision assessment can be described.

For a binary endpoint, the denominator matters as much as the numerator. The full enrollment of 27 does not identify the number included in the Arm B endpoint analysis. Participants may have had different follow-up availability, and the handling of participants who withdrew, had incomplete assessments, or otherwise lacked endpoint information can affect a fixed-time rate. The endpoint analysis population, missing-data rules, and any sensitivity analyses are not reported in the registry record. General good practice is to state these choices clearly because different denominators or missing-data assumptions can produce different interpretations.

The sample-size planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It sets the effect to detect as a stated fraction of the observed effect. For time-to-event outcomes, the stated planning approach uses the total number of events; for other outcomes, it gives participants per arm. These are planning illustrations based on an effect estimate, not observed power and not necessarily the study’s original design calculations. The registry record does not report the trial’s own sample-size justification. Since no primary endpoint effect estimate is posted, its relationship to any planning illustration cannot be evaluated from the registry record.

General power calculations describe the probability of detecting a specified effect under assumed conditions if that effect were present. They do not measure whether a completed study has demonstrated an effect, and retrospective calculations based on an observed estimate can be especially difficult to interpret. A planning number should instead be read as conditional on its assumptions, including the target effect, significance level, allocation, and statistical approximation. The registry record does not report the assumptions used in the original study’s own planning or any enrollment revision.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple probability model assumes. It can make standard errors too small and confidence intervals too narrow if ignored. The registered primary endpoint is described as a participant count underlying a binary rate, not as a count of repeated events. The registry record does not report an over-dispersion assessment or a model-based analysis for the primary outcome; no such method should be presumed.

The registry lists one outcome measure and zero analyses. This distinction is important: an endpoint definition states what was intended to be measured, while an analysis result reports what was estimated from collected data. The outcome entry alone does not provide a statistical estimate. No hypothesis test, p-value, confidence interval, adjusted analysis, or analysis-specific sample size is reported in the registry record. General statistical concepts can clarify how such results would be interpreted, but they cannot supply the missing result.

The posted safety figures are also descriptive. Counts of participants at risk and affected do not, by themselves, specify event rates over person-time, establish statistical comparisons, or describe causality. A formal comparison would need a defined estimand, appropriate analysis population, and suitable uncertainty estimates. The registry does not report such a safety comparison. In particular, the non-randomized design and differing arm schedules make a simple numerical contrast across arms insufficient to attribute differences to treatment schedule.

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("Arm B")
n      <- c(14)
events <- c(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  Arm B  14  3  21.4  4.7  50.8  7.6  47.6  7.8  48.1

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when several outcomes, time points, groups, or statistical tests are examined. In general, repeated testing can increase the chance of a false-positive finding unless the analysis plan accounts for it. The registry lists one outcome measure, the two-month progression-free survival rate, and no analyses. It does not report a multiplicity adjustment or a broader testing hierarchy. The protocol’s full outcome set and any prespecified testing strategy are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The endpoint depends on whether participants remained progression-free through the specified follow-up period, but the entry does not state how incomplete follow-up, withdrawals, or unavailable assessments were handled. It also does not report whether an analysis required a particular follow-up duration or used imputation, censoring, or sensitivity analyses. These are not interchangeable choices: as a general principle, the assumptions used for unavailable outcomes affect interpretation of a fixed-time rate.

The endpoint population is restricted to Arm B, but the registry record does not report the number included in that analysis or define the analysis population further. Overall enrollment is 27, which does not identify the endpoint denominator. The analysis populations for efficacy and safety, including any exclusions or deviations from the planned population, are not reported in the registry record. No interim-analysis conduct, decision rules, or statistical analysis plan is reported beyond the brief design label. These gaps prevent a fuller assessment of selection, missingness, and multiplicity.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (66.7%), atrial fibrillation (33.3%), cardiac failure (33.3%), ascites (33.3%), disease progression (33.3%).

The registry lists serious adverse event figures separately for Arms A, B, and C. The respective numbers at risk are 10, 14, and 3; the numbers affected are 7, 4, and 3. Deaths are listed as 5, 4, and 2, respectively. These are counts as recorded, not comparative estimates with uncertainty intervals. The registry record does not state whether the deaths were considered treatment-related, their timing, or their causes.

The listed top serious adverse event terms are dyspnoea (66.7%), atrial fibrillation (33.3%), cardiac failure (33.3%), ascites (33.3%), disease progression (33.3%), and oedema peripheral (33.3%). These percentages are reported as serious terms; the registry entry does not clarify the denominator or whether they represent participants, events, or another reporting unit. They should therefore be read as listed terms and percentages rather than as directly comparable arm-specific risks.

Other adverse event figures list 10 affected among 10 at risk in Arm A, 14 among 14 in Arm B, and 3 among 3 in Arm C. They are descriptive counts. The record does not provide event timing, severity breakdowns for these other events, exposure-adjusted rates, or a causal assessment. Because allocation was non-randomized and the arms differed, these counts do not establish a safety ranking between schedules.

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

The record establishes that a Phase II study of dordaviprone (ONC201) was registered for women with recurrent or metastatic Type II endometrial cancer after at least 1 prior chemotherapy regimen. It identifies the planned primary endpoint as progression-free survival at 2 months and states that only Arm B participants were analyzed for that outcome. It also documents three arm descriptions, differing schedules and biopsy requirements, an overall enrollment of 27, and a terminated status.

It does not report the numerical result for the primary endpoint. There is no posted count of participants meeting the progression-free definition, no reported rate, and no confidence interval. Accordingly, the record cannot establish the observed two-month progression-free survival rate or how precisely it was estimated. This absence is not itself a finding that the endpoint was met or not met.

Nor does the record support a causal comparison among the arms. The allocation was non-randomized, the study was open-label, and the registry explicitly notes that the arms are not a like-for-like control comparison. Differences in treatment schedule, biopsy requirements, participant characteristics, or follow-up could all matter to comparisons; the record does not provide enough information to separate those influences.

The safety counts document reported serious and other adverse event figures, along with listed serious terms and deaths. They do not show whether events were caused by treatment or permit a complete comparison of risk between arms. The reason for termination, missing-data methods, analysis populations, original sample-size justification, and detailed statistical plan are not reported in the registry record. The appropriate interpretation is therefore descriptive and limited to what the registry records, without drawing a treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registry record pairs a defined fixed-time efficacy endpoint with no posted analysis result. That distinction is central: specifying an endpoint does not provide evidence about its value. For clinical researchers, a registry entry can document what was intended to be assessed while still leaving the estimate, its uncertainty, and the underlying analysis unavailable.

The endpoint was assigned only to Arm B, while the intervention descriptions list three arms. The brief summary calls the study a 2-arm trial, and the registry does not explain the difference. This makes clear reporting of arm structure and analysis populations especially important. Readers need to know which participants contributed to an endpoint and why, rather than treating overall enrollment as the denominator for every outcome.

The non-randomized design also illustrates a general interpretive issue. A collection of arm-specific figures is not equivalent to a randomized comparison. When treatment groups differ in schedule or study procedures, descriptive contrasts do not isolate the effect of treatment schedule. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjustment method or an analysis result.

Finally, the terminated status and the absence of analysis details highlight the value of complete reporting. The registry record does not state why the study ended, how incomplete follow-up was handled, or what decision rules accompanied the Simon two-stage label. These omissions do not answer the clinical question, but they define the limits of what can be concluded from the posted 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.

Several limitations are specific to the information recorded for this study. The brief summary describes a 2-arm trial, whereas the intervention descriptions list Arms A, B, and C. The registry record does not explain this difference, report how the arms relate to the staged design, or give arm-specific enrollment totals in the trial description. Although overall enrollment is 27, that number should not be treated as the denominator for the Arm B primary endpoint.

The only listed outcome measure is progression-free survival rate at 2 months, and no analysis is listed. The registry record does not report the primary endpoint count or rate, confidence interval, assessment criteria for progression, analysis population details, or handling of missing follow-up. The reason for termination is not reported in the registry record. Neither the original sample-size justification nor detailed Simon two-stage decision rules are reported.

The study’s non-randomized, open-label design limits interpretation of arm-to-arm differences. The arms also differ in dosing schedule and biopsy requirements, and the record says they are not a like-for-like control comparison. The safety figures are descriptive, with no posted causal attribution or uncertainty estimates. The serious-term percentages do not have a stated denominator in the registry entry. These limitations prevent a fuller evaluation of efficacy, precision, comparative effects, and safety from the registry record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ONC201 in Recurrent or Metastatic Type II Endometrial Cancer Endometrial Cancer — NCT03485729.
• Registry record last updated 2024-12-24; status last verified 2024-12.
• Results first posted 2024-12-24.
• 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 identifies NCT03485729 as a Phase II, non-randomized, open-label, parallel study of dordaviprone (ONC201) in recurrent or metastatic Type II endometrial cancer. The brief summary describes women who had failed at least 1 prior chemotherapy regimen and calls the study a Simon two-stage design. Overall enrollment is 27; the study is listed as terminated, with a primary completion date of 2023-01-19.

The primary endpoint was progression-free survival rate at 2 months, defined as progression-free survival for >8 weeks (>56 days) after treatment initiation. Only Arm B participants were analyzed for this outcome. The registry lists one outcome measure and no analyses, so the primary endpoint result is not reported in the registry record. Three arm descriptions are listed, despite the brief summary’s reference to a 2-arm study. Serious and other adverse event counts are recorded by arm, but the posted information does not establish causality or support a like-for-like arm comparison.