Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors (NCT06169124), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study asks whether objective responses were observed after treatment with darolutamide, leuprolide acetate, and exemestane in patients with recurrent adult-type ovarian granulosa cell tumors. It is a phase II study registered as NCT06169124. The primary endpoint is objective response rate, defined as complete or partial response under Response Evaluation Criteria in Solid Tumors version 1.1, within 9 months of initiating study treatment.

The study also lists duration of response, progression-free survival, overall survival, and adverse events as secondary outcomes. Those outcomes address distinct questions: how long response lasts, how long patients remain alive without progression, overall survival, and the occurrence of adverse events. Their numerical results are not reported in the registry record. The central statistical limitation is therefore not uncertainty around a posted effect estimate, but the absence of that estimate in the registry results.

3. Trial Design

NCT06169124 is a phase II, single-group study sponsored by the National Cancer Institute (NCI). The registry lists enrollment of 17 participants and status as completed. The study started on 2024-02-08, and the primary completion date is 2026-02-10. These dates describe the registry record and do not establish when results became available.

All participants are assigned to the treatment combination: exemestane, darolutamide, and leuprolide acetate. The record describes oral exemestane once daily and oral darolutamide twice daily, starting during the period from days -14 to -7 before cycle 1, day 1, and continuing on days 1-28 of each cycle. Leuprolide acetate is administered intramuscularly on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. The treatment description ends mid-sentence after “Patients”; further details of that description are not reported in the registry record.

Because the design has a single group, the study can describe outcomes among people receiving the combination, but it cannot estimate a randomized treatment contrast. Allocation is listed as not applicable and masking as none. No separate comparator arm is listed. Differences between outcomes in this study and outcomes in another population or study would not constitute a randomized comparison.

The primary endpoint is objective response rate within 9 months of initiating treatment. The registry defines response using complete or partial response assessed by Response Evaluation Criteria in Solid Tumors version 1.1. The population description excludes a participant who did not initiate leuprolide acetate, but the number included in the endpoint analysis is not reported in the registry record. The record says exact 95% confidence limits accounting for interim analysis will be provided in the final report; the results and those limits are not reported in the registry record.

Procedures listed include biospecimen collection and imaging such as chest radiography, computed tomography, magnetic resonance imaging, and positron emission tomography. The registry does not state in the listed material how each procedure contributes to endpoint assessment. Details of sample-size justification, interim analyses, and a complete statistical analysis plan are not reported in the registry 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients enrolled and completed the study therapy. One patient was excluded due to not initiating leuprolide acetate.

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 Objective Response Rate (ORR), measured over Within 9 months of initiating study treatment.

The primary endpoint is objective response rate (ORR), expressed as a count of participants with a complete response or partial response. Response is assessed using Response Evaluation Criteria in Solid Tumors version 1.1, and the assessment window is within 9 months of initiating study treatment. The primary endpoint population is described as patients enrolled and completing study therapy; one patient was excluded because leuprolide acetate was not initiated.

In general, objective response rate is a binary endpoint at the participant level: each participant is classified according to whether a qualifying response occurred within the specified assessment window. A response count can be translated into a proportion only when the relevant analysis denominator is known. The registry record does not report the response count, the denominator used for the final analysis, or the resulting response rate. It therefore does not support a numerical estimate of how frequently response occurred.

The endpoint is useful for describing tumor response over a defined period. It is distinct from duration of response, which concerns how long a response persists, and from progression-free survival and overall survival, which concern time-to-event outcomes. The registry lists these as secondary outcomes but does not report their results in the record.

The registry states that exact 95% confidence limits accounting for interim analysis will be provided in the final report. A confidence interval, in general, represents uncertainty around an estimated quantity under the assumptions of the statistical method. The actual limits and the method used to account for interim analysis are not reported in the registry record. Without the count, denominator, and interval, the precision of the primary endpoint estimate cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on matching the method to the question and outcome. This study’s primary outcome is a participant-level binary response: complete response or partial response within 9 months. The registry states that response is assessed using Response Evaluation Criteria in Solid Tumors version 1.1. For such an endpoint, the central descriptive quantities are the number meeting the response definition and the number assessed in the endpoint population. The registry record does not report those values or the resulting response estimate.

What does a response proportion describe?

In general, a response proportion describes the share of an analyzed population meeting a prespecified response definition during a stated time window. It is a summary of observed participants, not a direct statement about every person with the condition. The interpretation depends on the endpoint definition, the observation window, how missing assessments are handled, and who is included in the analysis. The record gives the response definition and time window, but the final count, denominator, and missing-data handling are not reported in the registry record.

The primary population is described as patients enrolled and completing study therapy, with one patient excluded because leuprolide acetate was not initiated. That description identifies at least one aspect of the analysis population, but it does not give the number of participants completing therapy or a complete account of eligibility for the primary analysis. A participant who does not initiate one component of a combination may be handled differently under different analysis-population rules. The rule actually used for all participants is not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval communicates statistical uncertainty around an estimate, in this case a response proportion. Its width depends on features such as the amount of information and the statistical method. It does not describe the range of outcomes for individual participants, and it does not guarantee that the true value lies in a particular interval. The registry says exact 95% confidence limits accounting for interim analysis will be provided in the final report. The limits, the exact procedure, and the details of any interim analysis are not reported in the registry record. Without the response estimate and its interval, neither the observed magnitude nor its precision can be evaluated.

The choice of an exact interval is generally relevant when estimating a proportion from counts, especially when approximations may be less suitable. This is general statistical context; the registry does not give enough detail to identify the exact method used or its assumptions. The record’s statement about accounting for interim analysis does not describe how that adjustment was performed. No specific interim-analysis schedule, stopping rule, or adjustment method is reported in the registry record.

How does the single-group design affect interpretation?

In general, a single-group study estimates outcomes among participants treated under the study conditions. Without a concurrent control group, it does not produce a randomized estimate of the difference between treatment and control. The design also does not separate the contribution of each medication in the combination. This study is listed as single-group, with allocation not applicable and masking none. Therefore, an observed response count, if reported, would be descriptive of this enrolled population and treatment setting rather than a randomized contrast.

Secondary outcomes require different statistical summaries. Duration of response, progression-free survival, and overall survival are time-to-event outcomes. In general, these outcomes account for both whether an event occurred and the time until it occurred; interpretation can depend on follow-up and censoring. The registry lists the outcomes but does not report their estimates, event counts, follow-up summaries, or analysis methods. The incidence of adverse events is also listed, but its analysis population, grading approach, and summary rules are not stated in the registry information.

What can planning calculations establish?

General sample-size planning evaluates how much information a future study might require under stated assumptions. The planning illustrations associated with this analysis are described as two-sided, using significance level 0.05, equal allocation between two arms, and a normal approximation, with effects defined as fractions of an observed effect. For time-to-event outcomes, the stated quantity is a total number of events; for other outcomes, it is participants per arm. These are planning illustrations, not observed trial results and not evidence of achieved power.

The study itself is single-group, while the planning description assumes equal allocation between two arms. Such an illustration is therefore hypothetical and should not be mistaken for the actual trial design or the number enrolled in this study. The registry does not report the study’s own sample-size justification, target effect, or design assumptions. Numerical planning outputs are not reported in the registry record, so no values can be interpreted in this explanation.

Over-dispersion is a general concern for outcomes whose variability exceeds what a simple model assumes. If present, it can make uncertainty estimates too small under a model that ignores it. The primary endpoint is described as a participant count, but the registry record does not state that an over-dispersion model was used or identify a model-based analysis. This concept should not be read as a feature established for this trial.

Finally, statistical significance and clinical relevance are not interchangeable concepts. In general, an interval can convey uncertainty even when a threshold-based test is not reported, while the practical meaning of an estimate depends on context and the question being asked. The registry record does not provide the primary estimate or a hypothesis-testing result. Consequently, no conclusion about statistical significance, precision, or clinical importance can be drawn from the posted primary endpoint information.

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("Treatment (Exemestane, Darolutamide, Leuprolide Ac")
n      <- c(16)
events <- c(1)
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  Treatment (Exemestane, Darolutamide, Leuprolide Ac  16  1  6.2  0.2  30.2  1.1  28.3  1.5  28.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response rate as the primary outcome and duration of response, progression-free survival, overall survival, and incidence of adverse events as secondary outcomes. Testing or estimating several outcomes can raise multiplicity questions. In general, multiplicity procedures may be used to control the chance of misleading conclusions across a family of statistical tests. The registry record does not report whether such procedures were planned or applied, how outcomes were ordered, or whether any secondary outcomes were confirmatory.

The primary endpoint description says that exact 95% confidence limits accounting for interim analysis will be provided in the final report. The interim-analysis details and the method used to account for them are not reported in the registry record. The record does not state whether interim analyses were conducted, how many were planned, or whether the primary endpoint analysis was adjusted in another way. No further inference about interim monitoring is warranted.

The primary population is described as participants enrolled and completing study therapy, excluding one patient because leuprolide acetate was not initiated. This is relevant to missing-data interpretation because the endpoint denominator and analysis population determine how incomplete treatment or unavailable response assessments affect the estimate. The registry does not report the final denominator, the number with missing or unevaluable response assessments, or how such cases were handled. It also does not report whether participants were analyzed under any additional population definition.

In general, complete-case summaries can differ from analyses that account for missing outcomes, particularly if missingness is related to prognosis or treatment experience. That general concern does not establish that missing endpoint data occurred in this study. The extent and handling of missing data are not reported in the registry record.

Accordingly, the posted information is insufficient to assess multiplicity control, interim-analysis adjustments, or the robustness of the primary estimate to missing data. Those are reporting gaps, not evidence that the analyses were or were not conducted.

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: constipation (11.8%), vomiting (11.8%), anemia (5.9%), rectal pain (5.9%), small intestinal obstruction (5.9%).

The registry’s serious adverse-event summary lists 17 participants at risk and 7 affected participants. It also lists 10 participants with other adverse events and 5 deaths. These are separate summary counts as recorded; they should not be added together or treated as mutually exclusive categories unless the registry defines them that way. The record does not provide further detail on the timing, duration, severity grading, or outcome of each event.

The listed serious-event terms include constipation and vomiting, each reported as 11.8%, and anemia, rectal pain, small intestinal obstruction, and nausea, each reported as 5.9%. These percentages describe the registry’s reported terms; the record does not explain whether participants could contribute more than one event or how repeated events were counted. The percentages do not establish that an event was caused by treatment.

In general, safety counts in a single-group study describe events observed among treated participants. They cannot by themselves determine how the event frequency compares with what would have occurred without treatment or under another regimen. The record does not report a control group, an attribution breakdown, or sufficient event-level details to make that comparison. The counts should therefore be read as descriptive safety observations rather than comparative treatment effects.

The 5 deaths are listed in the safety summary, but the registry information does not specify causes or establish a relationship to study treatment. The safety figures also do not include enough context to infer the risk for an individual participant.

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

The study is designed to describe objective response after a combination of darolutamide, leuprolide acetate, and exemestane in recurrent adult-type ovarian granulosa cell tumors. The registry identifies the response definition, the assessment window, and the intended primary population. However, the primary response count, denominator, response rate, and confidence limits are not reported in the registry record. The posted information therefore does not show the numerical primary result.

If a response estimate is reported elsewhere in a final report, its interpretation would depend on the analysis population, response assessments, and interval method. The endpoint definition specifies complete or partial response under Response Evaluation Criteria in Solid Tumors version 1.1, within 9 months of initiating treatment. The record says the analysis population includes patients enrolled and completing study therapy, with one patient excluded for not initiating leuprolide acetate. It does not provide the final number analyzed or explain how other incomplete or unevaluable cases were treated.

The single-group design means there is no randomized control arm for a like-for-like comparison. Even if a response estimate were available, it would describe outcomes in the study group and would not, on its own, measure the difference attributable to treatment compared with another approach. Nor could the combination’s separate medication contributions be distinguished from one another.

The registry also lists secondary outcomes, including duration of response, progression-free survival, overall survival, and adverse events. Numerical results for these outcomes are not reported in the registry record. The safety counts provide descriptive information, but do not establish causality or a comparative risk.

Thus, the record defines an important statistical question and provides some design and safety information, while leaving the primary efficacy estimate and its precision unavailable. Absence of a reported result should not be interpreted as either evidence of benefit or evidence of no benefit. The appropriate interpretation is limited to the design and observations that the registry actually reports.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between a clearly defined endpoint and a reported endpoint result. The registry specifies objective response rate, the response criteria, the assessment window, and the intended population. Those details make the question understandable. But without the response count, denominator, estimate, or confidence limits, readers cannot assess the observed response frequency or how precise its estimate is.

The study also highlights the importance of analysis-population definitions. The registry describes the primary population as patients enrolled and completing study therapy, and notes exclusion of a patient who did not initiate leuprolide acetate. Enrollment is 17, but the endpoint denominator is not reported. A count of enrolled participants cannot substitute for a denominator defined by endpoint eligibility and assessment.

The single-group design clarifies another central issue: descriptive evidence and comparative evidence answer different questions. This design can report outcomes among participants receiving the combination, but it cannot make a randomized comparison with another treatment. That limitation applies even if outcome estimates are eventually reported. It is a feature of the design, rather than a matter that can be fixed by interpreting a single-group result more strongly.

Finally, the registry distinguishes the primary endpoint from time-to-event and safety outcomes, but the listed outcomes do not themselves communicate results. For readers, a complete interpretation requires estimates and uncertainty alongside endpoint definitions, analysis populations, and information about missing data and interim analyses. The record says exact 95% confidence limits accounting for interim analysis will be provided in the final report, while those details are not reported in the registry record.

The statistical importance of this record is therefore its transparent statement of the intended question and its limits: it identifies what was to be measured, but does not report the primary numerical answer.

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 specific to this study affect interpretation of the registry information. First, the primary endpoint result is not reported in the registry record. There is no response count, analysis denominator, response rate, or confidence interval. This prevents assessment of both the magnitude of the observed response and its statistical precision.

Second, the primary population is described as participants enrolled and completing study therapy, with one participant excluded for not initiating leuprolide acetate. The record does not state the final number who completed therapy or how other participants with incomplete treatment or response assessment were handled. The enrollment of 17 does not resolve that uncertainty.

Third, this is a single-group study with no randomized comparator. Outcomes among participants receiving the combination cannot establish a randomized difference from another treatment or a control condition. The design also cannot isolate the separate contributions of darolutamide, leuprolide acetate, and exemestane.

Fourth, the registry states that exact 95% confidence limits accounting for interim analysis will be provided in the final report, but does not report the limits or the interim-analysis approach. Details of the statistical analysis plan, sample-size justification, multiplicity procedures, and handling of missing data are not reported in the registry record.

Finally, selected serious adverse-event counts and terms are listed, but the record does not provide enough information to establish treatment attribution, event timing, or a comparative safety profile. Secondary outcome results are also not reported. These limitations constrain interpretation of the posted information and should not be replaced by assumptions about unreported analyses or findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors — NCT06169124.
• Registry record last updated 2026-11-03; status last verified 2026-10.
• Results first posted 2026-11-03.
• 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

NCT06169124 is a completed phase II, single-group study sponsored by the National Cancer Institute (NCI), with enrollment of 17 participants. It evaluates darolutamide with leuprolide acetate and exemestane for recurrent adult-type ovarian granulosa cell tumors. The registry lists a start date of 2024-02-08 and a primary completion date of 2026-02-10.

The primary endpoint is objective response rate within 9 months, defined as complete or partial response under Response Evaluation Criteria in Solid Tumors version 1.1. The stated primary population includes patients enrolled and completing study therapy; one patient was excluded because leuprolide acetate was not initiated. The response result and exact 95% confidence limits are not reported in the registry record.

Secondary outcomes include duration of response, progression-free survival, overall survival, and adverse events. The safety summary lists 7 participants with serious adverse events, 10 with other adverse events, and 5 deaths among 17 at risk. The study has no randomized comparator, and the registry does not report the statistical analysis plan, missing-data methods, or interim-analysis details.