A Study of ENMD-2076 in Ovarian Clear Cell Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of ENMD-2076 in Ovarian Clear Cell Cancers (NCT01914510), a na phase 2 study. The primary outcome is Six Month Progression Free Survival Rate.

2. Clinical Question

3. Trial Design

This was a Phase 2 study of ENMD-2076 in ovarian clear cell carcinoma. It was conducted as a single-group study, rather than as a randomized comparison. The registry lists allocation as NA and masking as none. Accordingly, the study can describe outcomes recorded among participants receiving the study drug, but it does not provide a concurrent control group for estimating a treatment contrast.

The listed intervention was ENMD-2076, an oral drug. The arm description states that participants would take 275 mg once daily, while patients with a body surface area less than 1.65 m2 would receive a starting dose of 250 mg once daily. The arm text contains the name ENMD-2067 in its dosing sentence, whereas the intervention name is ENMD-2076; the registry record does not explain this difference in wording.

The record lists an enrollment of 40. It states that 38 were deemed eligible for evaluation and that two participants did not complete one cycle of therapy and were considered not evaluable. The criteria used to define evaluability beyond this statement, and the exact analysis population for the primary endpoint, are not reported in the registry record.

The study status is completed. The listed start date is 2013-09 and the primary completion date is 2017-01. The sponsor is University Health Network, Toronto. Secondary outcomes include time to disease progression and levels of certain proteins and gene expression compared with patient outcome following treatment. Details of the statistical analysis plan, including prespecified adjustment methods or interim analyses, 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

Analysis population for the primary outcome, as defined in the registry: Of the 40 participants enrolled, 38 were deemed eligible for evaluation. Two patients did not complete one cycle of therapy and were considered not evaluable.

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: Of the 40 participants accrued onto trial, 38 were evaluable. Two participants did not complete therapy, and were deemed unevaluable

6. Primary Endpoint

The registry lists the primary outcome as Six Month Progression Free Survival Rate, measured over Response will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1. Progression free survival is the time from the first day of treatment to the first observation of disease progression or Death/last F/U..

The primary endpoint is titled six-month progression-free survival rate. Progression-free survival (PFS) is defined in the registry as the time from the first day of treatment to the first observation of disease progression, death due to any cause, or last follow-up. Participants who were alive and free of progression at last follow-up were to be censored at that time. The record also says response was determined using Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1.

In general, a time-to-event endpoint describes how long it takes for a defined event to occur. A six-month rate is intended to summarize the proportion of an analysis population meeting a specified event-free status at that time point. Censoring is used when a participant’s event status is not observed through the full period; it allows the available follow-up to contribute without treating the last observed status as if it continued indefinitely.

The endpoint can describe disease progression or death within a defined follow-up framework, but interpretation depends on the event definition, follow-up, and analysis population. The registry record does not report the six-month PFS estimate, its confidence interval, or a test result. It also does not provide enough detail to establish how the endpoint was calculated from participant-level follow-up.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the question a study design can answer. This study is listed as single-group, with allocation NA and masking none. It therefore records outcomes in a group receiving ENMD-2076 rather than estimating a randomized difference between treatment groups. In general, random allocation helps balance measured and unmeasured prognostic factors across groups on average. Without a randomized comparator, a change or event pattern in the treated group cannot by itself identify what would have happened under an alternative condition.

What does progression-free survival measure?

The primary outcome is the six-month progression-free survival rate. The registry defines PFS as time from the first treatment day until first observation of disease progression, death from any cause, or last follow-up, with participants alive and free of progression censored at last follow-up. The record says response was determined using RECIST criteria 1.1. In general, time-to-event analysis incorporates both event times and follow-up that ends before an event is observed. Censoring distinguishes a participant known to be event-free through the last observation from a participant whose later status is unknown.

A six-month rate summarizes event-free status at a specified time point, rather than merely counting all events without regard to when they occurred. Its interpretation depends on the exact endpoint definition, timing and completeness of follow-up, and how censored observations were handled. Although the registry describes the endpoint and censoring rule, it does not report the estimated rate, the confidence interval, or details of the calculation. No result can therefore be reconstructed from the endpoint definition alone.

How should uncertainty be understood?

In general, a confidence interval expresses the statistical uncertainty associated with an estimate under a specified analysis method. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. It does not remove possible bias from the study design, participant selection, incomplete follow-up, or outcome measurement. The registry record does not report a confidence interval for the primary endpoint, so the precision of the six-month PFS result cannot be described.

In general, a p-value evaluates how compatible data are with a specified null hypothesis under the assumptions of a statistical test. It is not a measure of the size or clinical importance of an effect, and it does not convey precision as directly as an interval estimate. No primary endpoint p-value or statistical test is reported in the registry record. The statistical plan and any prespecified hypothesis are also not reported.

What do the planning assumptions mean?

The planning illustrations are described as calculations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. These are planning assumptions, not a description of this trial’s single-group design. The record’s general rule is that time-to-event planning gives a total number of events using the Schoenfeld method, while other planning outputs give participants per arm. The calculated illustration values and the observed effect are not reported in the registry entries, so those quantities cannot be interpreted numerically.

In general, a sample-size illustration asks what scale of future study might be required under assumed effect size, variability, significance level, allocation, and method. Altering the assumed target effect changes the planning question. Such values are not observed participant outcomes and are not observed power. Observed power is not a substitute for reporting the estimate and its uncertainty; interpretation should focus on the result and its precision when those are available. The stated equal-allocation, two-arm assumption should not be mistaken for the design of this single-group trial.

Why does the single-group design matter?

In general, a concurrent control group provides a basis for comparing outcomes over the same study period. Randomization supports causal interpretation by reducing systematic differences between assigned groups, while masking can reduce some forms of measurement or conduct bias. Here, the record lists no comparator and no masking. It therefore supports descriptive reporting of outcomes in the ENMD-2076 group, but not a randomized treatment effect estimate. The registry does not report enough information to assess other possible sources of bias or the details of outcome assessment.

The record also distinguishes enrollment from evaluability: 40 participants enrolled, 38 were deemed eligible for evaluation, and two were considered not evaluable after not completing one cycle of therapy. In general, excluding participants from an endpoint analysis can affect interpretation, especially if exclusion is related to prognosis or outcomes. The registry does not report the full analysis population definition, the primary endpoint denominator, or sensitivity analyses addressing excluded participants. These omissions constrain assessment of the analysis, rather than allowing an assumption about how the exclusions affected the result.

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("ENMD-2076")
n      <- c(38)
events <- c(8)
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  ENMD-2076  38  8  21.1  9.6  37.3  11.1  36.3  11.1  36.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes, including time to disease progression and levels of certain proteins and gene expression compared with patient outcome following treatment. It also lists four outcome measures. However, the statistical plan for testing or estimating these outcomes is not reported in the registry record. In particular, it is not reported whether the study prespecified a hierarchy of outcomes, adjusted for multiple comparisons, or treated secondary analyses as exploratory.

In general, when multiple hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis accounts for multiplicity. Adjustment is not always appropriate for every descriptive or exploratory objective, but the intended interpretation should be clear. Without a reported plan, the strength of any unreported or exploratory findings cannot be evaluated. No numerical primary result or secondary outcome results are available for assessing multiplicity in this record.

The registry states that two participants did not complete one cycle of therapy and were considered not evaluable, while 38 were deemed eligible for evaluation. The exact primary endpoint analysis population, missing-data handling beyond the stated censoring rule, and sensitivity analyses are not reported in the registry record. In general, censoring for last follow-up is part of time-to-event analysis; it differs from assuming that an unobserved outcome is event-free indefinitely. Whether censoring is informative depends on why follow-up ended and on the analysis assumptions. The record does not provide details to evaluate those assumptions.

The protocol’s sample-size justification, interim analyses, prespecified statistical analysis plan, and any rules for handling missing outcome data are not reported in the registry record. The planning illustrations described separately are not evidence that those methods formed the original study plan.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (5.0%), confusion (5.0%), abdominal pain (2.5%), vaginal fistula (2.5%), pulmonary embolism (2.5%).

The registry safety summary lists 10 participants with serious adverse events among 40 at risk in the ENMD-2076 group. It lists 40 participants with other adverse events among 40 at risk, and deaths are listed as 0. The serious-event terms shown include Hypertension at 5.0%, Confusion at 5.0%, Abdominal Pain at 2.5%, Vaginal Fistula at 2.5%, Pulmonary Embolism at 2.5%, and Nausea & Vomiting at 2.5%. These are the posted registry summaries, not a comparison between treatment groups.

In general, an at-risk count describes the participants included in the relevant safety summary, while an affected count describes those recorded with an event under that summary. Serious adverse events and other adverse events are separate categories in the registry data; the counts should not be treated as interchangeable. The listed term percentages are reproduced as reported and should not be converted into counts or combined without further information about coding and denominators.

These figures are descriptive. They do not establish that an event was caused by ENMD-2076, and the absence of listed deaths does not answer every safety question. The registry record does not report event timing, duration, severity grades, exposure-adjusted rates, or a comparator. It also does not provide enough detail to determine whether participants could have more than one event or how repeated events were represented.

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

The record describes a completed Phase 2, single-group study of oral ENMD-2076 for ovarian clear cell carcinoma. Its primary endpoint was the six-month progression-free survival rate, with PFS defined from the first day of treatment to disease progression, death from any cause, or last follow-up. It also records that 40 participants enrolled and that 38 were deemed eligible for evaluation; two participants did not complete one cycle of therapy and were considered not evaluable.

Those details establish the study framework, but the registry record does not report the primary endpoint estimate. Without the six-month rate and an uncertainty interval, the magnitude and precision of the observed PFS result cannot be described. The record also does not report a primary endpoint test result, so statistical evidence relative to a stated hypothesis cannot be assessed.

Because there is no comparator arm and no randomization, this study does not estimate a randomized difference between ENMD-2076 and another treatment. In general, a single-group outcome may be informative as a description of what was observed in enrolled participants, but it cannot isolate the contribution of the intervention from other influences on outcomes. The record does not support a conclusion about comparative effectiveness.

The safety summary records serious adverse events, other adverse events, and deaths for the study group. These entries describe events recorded in the registry; they do not prove that the drug caused or did not cause an event. Nor do they provide a comparative safety estimate. Further information about event definitions, timing, exposure, and participant-level overlap is not reported in the registry record.

The planning illustrations are based on the observed effect and stated assumptions, but their numerical estimates and the observed effect are not reported in the registry entries available for interpretation. Planning calculations are hypothetical design aids, not observed outcomes or observed power. Taken together, the record allows a careful account of design, endpoint definitions, evaluability, and posted safety counts, while leaving the primary efficacy result and its statistical precision unreported.

14. Why This Trial Matters Statistically

This trial illustrates why design and reporting details are necessary for statistical interpretation. The registry identifies a Phase 2 single-group study and names a six-month progression-free survival endpoint, but it does not report the endpoint estimate or its uncertainty. Knowing the endpoint definition is important, yet it cannot substitute for the result itself. Without an estimate and a measure of precision, readers cannot assess what range of outcomes is compatible with the data.

The single-group structure also defines the scope of the evidence. The record has no randomized comparator, so it cannot estimate a randomized contrast. This matters because outcome patterns in a treated group can reflect influences other than treatment. General statistical reasoning distinguishes a descriptive result within a group from a comparative estimate designed to address differences between interventions.

The record’s distinction between enrolled and evaluable participants is another important reporting feature. It states that 40 enrolled, 38 were deemed eligible for evaluation, and two did not complete one cycle of therapy and were considered not evaluable. A reader needs to know which participants contributed to each endpoint analysis and how missing follow-up was handled to assess how the result corresponds to the enrolled group. Those analysis details are not reported in the registry record.

Finally, the safety counts and planning assumptions answer different questions. Safety entries describe adverse events recorded in the study group, while sample-size illustrations describe hypothetical planning under stated assumptions. Neither supplies the missing primary endpoint estimate. Keeping these kinds of information separate helps prevent a descriptive safety count or a planning calculation from being mistaken for evidence about a comparative treatment effect.

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 main trial-specific limitation in interpreting the posted record is that the primary endpoint result is not reported. Although the endpoint is titled six-month progression-free survival rate and its time origin, event definition, and censoring rule are described, there is no rate estimate, confidence interval, or test result. The record therefore does not permit an assessment of the primary endpoint’s magnitude or precision.

The study is single-group, with allocation listed as NA and masking listed as none. There is no like-for-like control comparison. This prevents estimation of a randomized between-group treatment contrast and leaves outcomes open to influences that a concurrent control could help address. The record does not report other design or analysis details that would resolve this limitation.

The population flow is only partly described. The record states that 40 enrolled, 38 were deemed eligible for evaluation, and two did not complete one cycle and were considered not evaluable. The exact endpoint denominator, complete analysis population definition, reasons for any other missing observations, and sensitivity analyses are not reported in the registry record. The potential implications of these details cannot be quantified.

The safety summary is also limited to descriptive entries. Event timing, duration, severity grading beyond the serious-event classification, exposure-adjusted analyses, and a comparator are not reported. Thus, the listed events cannot be used to estimate a comparative safety difference or establish causation.

Finally, the protocol’s statistical plan, sample-size justification, interim analysis procedures, and multiplicity approach are not reported in the registry record. Planning illustrations described using an observed effect do not fill these gaps, particularly when their numerical results and the observed effect are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of ENMD-2076 in Ovarian Clear Cell Cancers — NCT01914510.
• Registry record last updated 2019-12-13; status last verified 2019-12.
• Results first posted 2019-12-13.
• 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

This completed Phase 2 study evaluated oral ENMD-2076 in ovarian clear cell carcinoma using a single-group design. Allocation is listed as NA and masking as none. The registry records enrollment of 40, with 38 deemed eligible for evaluation; two participants did not complete one cycle of therapy and were considered not evaluable.

The primary endpoint was the six-month progression-free survival rate. PFS was defined from the first day of treatment to disease progression, death from any cause, or last follow-up, with participants alive and progression-free censored at last follow-up. Response was to be determined using RECIST criteria 1.1. The primary endpoint estimate and its precision are not reported in the registry record.

The safety summary lists serious adverse events in 10 participants among 40 at risk, other adverse events in 40 among 40 at risk, and 0 deaths. Because the study has no comparator, these entries are descriptive and do not establish a comparative treatment effect or event causation.