A Study of Onapristone ER Alone Or In Combination With Anastrozole in Gynecologic Cancers That Respond to Progesterone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Onapristone ER Alone Or In Combination With Anastrozole in Gynecologic Cancers That Respond to Progesterone (NCT03909152), a non-randomized phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

The study asks whether response was observed during treatment with onapristone ER, used alone or alongside anastrozole, in these progesterone receptor-positive gynecologic cancers. It is a phase 2 study with non-randomized allocation and no masking. Its structure is therefore descriptive rather than a randomized test of whether one regimen is better than another. In particular, the disease groups differ, and the treatments were not assigned through a randomized comparison.

The registry lists enrollment of 34 and describes treatment groups for three cancer types, including a granulosa cell group marked closed. It does not report the number of participants who met the endpoint in any group. As a result, the central response question cannot be answered from the posted results. The record also does not report a response estimate, its uncertainty, or a statistical test for the primary endpoint.

3. Trial Design

This is a phase 2, completed, parallel-group study sponsored by Memorial Sloan Kettering Cancer Center. The registry lists non-randomized allocation and no masking. Enrollment is 34. The registry dates the study start as 2019-05-02 and primary completion as 2024-09-03.

The record describes four disease-group entries. Participants in the progesterone receptor-positive low grade serous ovarian cancer and endometrioid endometrial cancer groups were to receive onapristone ER 50 mg by mouth twice daily, about 12 hours apart. The granulosa cell tumor group marked closed has the same onapristone ER regimen. A separate progesterone receptor-positive granulosa cell ovarian cancer group was to receive onapristone ER 50 mg twice daily with anastrozole 1mg once daily in the morning. The descriptions state that treatment began on Day 1 of Cycle 1 and that a cycle was 28 days.

These groups do not form a randomized comparison. The record does not describe random assignment, masking, or a common control group. Differences between group outcomes, if results were available, could reflect differences in cancer type or other group characteristics as well as treatment. The registry record does not report details of treatment adherence, treatment duration, or whether participants could change treatment.

The study status is completed, but completion alone does not establish that each planned analysis was performed or reported. The registry lists one primary outcome measure and no posted analyses. It does not report the protocol’s sample-size justification, the planned statistical model, or an analysis plan.

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:

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 Overall Response Rate, measured over within 36 weeks.

The primary endpoint is Overall Response Rate, expressed in the registry as a count of participants. It is assessed within 36 weeks and uses response categories based on RECIST. The description defines overall response as complete response plus partial response. Complete response means disappearance of all target lesions; partial response means a >=30% decrease in the sum of the longest diameters of target lesions. The description says assessment was by MRI.

Response categories provide a way to describe whether measured target lesions changed according to prespecified criteria. Combining complete and partial responses into an overall response measure gives a count of participants meeting either category during the stated timeframe. This kind of endpoint is used in clinical research to characterize tumor response, but by itself it does not describe how long a response lasts, whether disease later progresses, or how participants feel or function.

There is a terminology inconsistency in the registry record: the primary endpoint title refers to RECIST 1.1, while its description refers to RECIST v1.0. The record does not explain this difference. It does not report the number of complete or partial responses, an overall response count, or a response rate. Although the endpoint is titled Overall Response Rate, the listed unit and parameter indicate a count of participants; the registry record does not provide a percentage estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does non-randomized allocation mean?

In a randomized trial, a chance-based process assigns participants to treatment groups. General statistical reasoning: randomization helps balance measured and unmeasured participant characteristics across groups on average, supporting a more credible causal comparison. This study is listed as non-randomized, so that protection does not apply. The registry record does not report how treatment or group assignment was determined.

The parallel structure means the record describes separate groups receiving their assigned regimens, rather than a design in which each participant is described as receiving each regimen in sequence. But parallel groups do not necessarily provide a valid treatment comparison. Here, the groups are distinguished by cancer type and regimen, and there is no randomized allocation. Any contrast between them could reflect differences in disease group as well as differences in treatment.

What does the primary endpoint count?

The endpoint is a count of participants meeting the overall response definition within 36 weeks. General statistical reasoning: a count is interpretable only alongside a clearly defined analysis population and the number assessed. A response proportion would also require a stated denominator. The registry record does not report the endpoint count, an analysis denominator, or a response proportion, so none can be interpreted from the posted results.

The response definition combines complete response and partial response. Those categories are based on changes in target lesions, using the criteria stated in the registry record. An endpoint based on response is distinct from a time-to-event endpoint: it does not, by itself, describe when progression occurs or how long a response persists. The record does not report those outcomes as primary results.

The registry labels the endpoint RECIST 1.1, but the descriptive text refers to RECIST v1.0. Because the record does not explain the discrepancy, readers cannot determine from this entry which version governed endpoint assessment. The description also specifies MRI assessment but does not report assessment procedures, independent review, or how ambiguous assessments were handled.

Why does the lack of posted analyses matter?

The registry lists no analyses. That means it does not report an estimate with a confidence interval, a hypothesis test, or an adjusted model for the primary outcome. General statistical reasoning: a point estimate describes the observed effect or event frequency, while an interval estimate conveys sampling uncertainty under its assumptions. Neither can be assessed when the outcome result and analysis population are absent.

A p-value, in general, evaluates how compatible data are with a specified statistical model and null hypothesis. It does not measure the size or clinical importance of an effect. No p-value or analysis model is reported for the response endpoint, so no significance claim can be made from the registry record. The record also does not state a null hypothesis, significance level for the primary endpoint, or whether an analysis would be one-sided or two-sided.

General statistical reasoning: over-dispersion matters when counts vary more than a chosen model expects, because a model that understates variability can produce confidence intervals that are too narrow and tests that overstate evidence. The registry does not report a count model or dispersion estimate, and the primary endpoint is a participant count rather than a reported rate model. There is no basis in the record to identify whether over-dispersion was assessed or relevant to the sponsor’s analysis.

How should planning illustrations be read?

General statistical reasoning: a sample-size calculation is a planning exercise, not a finding about the observed trial. The record’s planning assumptions describe an illustration using the observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation, with the effect set to a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm. These assumptions do not establish that the trial was designed or powered according to that illustration.

The trial itself is non-randomized and includes multiple disease groups and regimens, while the illustration assumes equal allocation between two arms. Those are different structures. Without the relevant outcome estimate and a corresponding comparison, the illustration cannot be treated as an observed power calculation or as evidence that the study could detect a particular effect. The registry record does not report the trial’s own sample-size justification or statistical planning assumptions.

General statistical reasoning: observed power is not a substitute for reporting an effect estimate and its uncertainty. Once results are available, interpretation should focus on the estimated outcome and its precision rather than treating a retrospective power calculation as evidence. Here, the primary response result is not reported, so the planning illustration cannot resolve the missing efficacy analysis.

What can the safety counts establish?

The safety entries give counts of participants affected by serious adverse events and other adverse events within each registry group, along with death counts. These are descriptive summaries. General statistical reasoning: event counts are more informative when accompanied by clear definitions, observation periods, and denominators. The record lists participants at risk for the safety summaries, but does not provide details of exposure duration or an analysis comparing groups. Because the groups are non-randomized and differ by disease type and regimen, their counts do not establish comparative treatment effects.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no analyses. It does not report whether the study examined additional endpoints outside the registry entry, whether subgroup analyses were planned, or how multiple statistical tests were handled. The statistical plan and any approach to multiplicity are not reported in the registry record. Without that information, it is not possible to determine whether any planned adjustment for multiple comparisons was used or whether the primary endpoint was selected before data were examined.

The endpoint definition sets a timeframe of within 36 weeks, but the registry record does not describe how response assessments outside that timeframe were handled. It does not report the number of participants who had an assessment, the number lacking an assessment, reasons for missing assessments, or the rule used to classify missing outcomes. Missing-data methods are not reported in the registry record.

The record does not define the primary analysis population. It therefore does not state whether the response count would include everyone enrolled, participants who began treatment, or another group. Enrollment of 34 should not be assumed to be the denominator for the primary endpoint. The group-specific analysis populations and their response denominators are not reported.

Because the record reports no primary endpoint result or analysis, the effects of missing data, analysis-population choices, and multiplicity cannot be evaluated. These details are important for interpreting the reliability of a reported estimate, but they are not available in the registry record.

11. 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: abdominal pain (40.0%), small intestinal obstruction (20.0%), thromboembolic event (7.1%), syncope (7.1%), febrile neutropenia (7.1%).

The registry reports serious adverse event counts by group: 2 of 14 in the progesterone receptor-positive granulosa cell tumor group marked closed; 3 of 5 in the low grade serous ovarian cancer group; 0 of 1 in the endometrioid endometrial cancer group; and 3 of 14 in the granulosa cell ovarian cancer group. The record lists zero deaths in each group. These figures are descriptive counts, not the result of a statistical comparison.

For other adverse events, the registry lists 14 of 14, 5 of 5, 1 of 1, and 14 of 14 affected participants, respectively, across those same groups. The registry also lists abdominal pain at 40.0%, small intestinal obstruction at 20.0%, and thromboembolic event, syncope, febrile neutropenia, and fatigue at 7.1% each among its top serious adverse event terms. The denominator basis for those term percentages is not reported in the registry record.

General statistical reasoning: counts depend on the group size and the period during which participants were observed. Because the groups differ in cancer type and regimen and were not randomized, these entries do not support a like-for-like comparison of safety between treatments. The registry record does not describe exposure time, event definitions beyond the serious/other categories, or a comparative safety analysis.

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

The registry record establishes that a completed phase 2 study examined onapristone ER, alone or in combination with anastrozole, in progesterone receptor-positive gynecologic cancer groups. It specifies the primary endpoint as an overall response count within 36 weeks and gives a RECIST-based response definition. It also records group-level safety counts and deaths.

It does not report the primary response count or a response rate. There is no posted estimate of the outcome’s precision and no analysis of treatment differences. Therefore, the record does not establish whether an overall response was observed, how often it occurred, or whether response differed by regimen. The absence of a reported result should not be interpreted as a result of zero responses.

The non-randomized design also limits causal interpretation. The disease groups are not like-for-like treatment arms, and the record does not describe a randomized control comparison. If comparative results were available, differences could not automatically be attributed to the treatment regimen. The registry entry does not provide an adjusted analysis to address this issue.

The safety counts describe events recorded in the registry groups, but they do not establish a comparative safety effect. The posted information does not include details such as exposure duration or an inferential analysis. The counts should be read as descriptive observations in the recorded groups.

In general, a trial record can help readers understand its population, design, interventions, endpoints, and reporting gaps. Here, it provides those design details but not the primary efficacy result or statistical analysis. No treatment recommendation follows from these registry data.

13. Why This Trial Matters Statistically

This study raises several statistical interpretation issues common to early-phase research. First, the registry’s non-randomized structure is central: separate disease groups and treatment regimens cannot be treated as randomized comparison arms. Statistical methods cannot, by themselves, remove the uncertainty created by non-random assignment, especially when the record does not report baseline characteristics or adjusted analyses.

Second, the primary endpoint is defined as a count of participants with a RECIST response within a specified timeframe, yet the result is not reported. A clear endpoint definition is useful, but interpretation requires the observed count and the number assessed. Without those, neither the response frequency nor its precision can be evaluated.

Third, the registry contains a discrepancy in the RECIST version named in the endpoint title and description. Consistent endpoint specification matters because readers need to know what criteria governed assessment. The record does not clarify the discrepancy.

Finally, the record distinguishes serious and other adverse events and gives counts by group, but provides no comparative safety analysis. The group sizes and disease types differ, and the registry does not report exposure duration. The entries therefore illustrate why descriptive event counts should not be confused with causal comparisons. These features make the study record useful for understanding design and reporting, while leaving the central response question unresolved in the posted results.

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 primary limitation for interpreting efficacy is that the registry record does not report the overall response result. It gives no response count, response rate, uncertainty interval, or statistical test. The primary analysis population and its denominator are also not reported, so the listed enrollment cannot be used to reconstruct an endpoint estimate.

Non-randomized allocation and the disease-specific groups limit comparisons between regimens. The record does not report baseline characteristics or an adjusted analysis that might address differences between groups. It also does not describe how participants were assigned to groups, whether treatment changed after starting, or how adherence was assessed.

The endpoint entry names RECIST 1.1 but describes RECIST v1.0, without explaining the difference. The record does not provide further details on response assessment, independent review, or handling of missing and unevaluable assessments. Missing-data methods and analysis-population definitions are not reported in the registry record.

The safety entries do not include exposure duration, detailed event definitions, or a comparative analysis. The denominator basis for the listed serious event term percentages is not reported in the registry record. These omissions limit interpretation of differences in safety counts across the disease groups.

The record lists no analyses and does not report the protocol’s statistical plan, sample-size justification, or multiplicity approach. The planning assumptions described for sample-size illustrations are not evidence of the study’s own design rationale. These reporting gaps prevent a full assessment of efficacy and statistical precision from the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Onapristone ER Alone Or In Combination With Anastrozole in Gynecologic Cancers That Respond to Progesterone — NCT03909152.
• Registry record last updated 2025-07-28; status last verified 2024-09.
• Results first posted 2025-07-28.
• 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

The registry describes a completed phase 2, non-randomized, unmasked, parallel-group study sponsored by Memorial Sloan Kettering Cancer Center. Enrollment is 34. The study evaluated onapristone ER alone or with anastrozole in progesterone receptor-positive gynecologic cancer groups.

The primary outcome is a count of participants with an overall response within 36 weeks, defined as complete response or partial response using the RECIST description. The registry record does not report the response result or any analysis. It lists serious adverse event counts, other adverse event counts, and zero deaths in each group.

The study’s non-randomized disease-group structure does not support a like-for-like treatment comparison. The statistical plan, analysis populations, and missing-data methods are not reported in the registry record.