Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies (NCT00856180), a na phase 2 study. The primary outcome is Therapy Completion Rate.

2. Clinical Question

The clinical question is therefore descriptive: among treated participants in this sequential-treatment study, what proportion reached the specified therapy-completion threshold? Completion was not defined as tumor response or long-term disease control. Participants could remain on treatment until disease progression on the combination regimen or unacceptable toxicity, while the primary endpoint focused on reaching a minimum duration of therapy.

Response and progression were assessed using different criteria depending on whether participants had measurable disease. The registry describes RECIST 1.0 criteria for measurable disease and Gynecologic Cancer Intergroup CA-125 (Rustin) criteria for participants without measurable disease. Those criteria inform assessment of disease status; they are not themselves the therapy-completion endpoint.

The registry also lists clinical benefit response rate, progression-free survival and overall survival as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. With no comparator group and no posted numerical primary result, the record does not establish how completion compares with another treatment or what effect the sequential strategy had on disease outcomes.

3. Trial Design

This was a phase 2, single-group study sponsored by Dana-Farber Cancer Institute. The registry lists enrollment of 20, describes allocation as NA, and reports no masking. The study status is completed. The record gives a start of 2009-02 and a primary completion of 2010-04.

The treatment strategy was sequential antiangiogenic blockade. Participants started with bevacizumab, and oral cyclophosphamide was to be added after progression through bevacizumab. The registry describes treatment as continuing until progression on the combination regimen or unacceptable toxicity. The listed drug interventions are bevacizumab and cyclophosphamide.

Disease was assessed serologically and radiologically every 2 cycles/6 weeks while participants were on treatment. The registry reports a median treatment duration for the study cohort of 7.5 months (range 0.7-20.7). This describes treatment exposure, not the primary endpoint result: the record does not state how many participants completed at least 3 months/4 cycles.

Because the design has a single group, outcomes are observed within the treatment cohort rather than estimated as a contrast between randomized groups. There is no like-for-like control comparison in the registry record. The findings can describe what was recorded among treated participants, but the design cannot separate treatment effects from other explanations for outcomes or provide a randomized estimate of comparative benefit.

The registry does not report a detailed statistical analysis plan, a sample-size justification, or information about interim analyses. Allocation procedures beyond the single-group designation are not reported in the registry record. No adjusted analysis is reported in the record. The study's listed secondary outcomes are clinical benefit response rate, progression-free survival and overall survival, but numerical outcome results 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: The analysis dataset is comprised of all treated participants.

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 Therapy Completion Rate, measured over Serologic and radiologic disease assessments occurred every 2 cycles/6 weeks on treatment. Median treatment duration for this study cohort was 7.5 months (range 0.7-20.7)..

The primary endpoint, therapy completion rate, is defined as the proportion of participants who completed at least 3 months/4 cycles of therapy. It summarizes whether participants reached a prespecified treatment-duration threshold. The primary-endpoint population is described as all treated participants.

This kind of endpoint can describe feasibility and treatment exposure: it indicates how often participants remained on therapy long enough to meet the stated threshold. It does not directly measure tumor shrinkage, progression-free survival, overall survival, or a comparison with another treatment. Participants could stop before the threshold for reasons that include disease progression or unacceptable toxicity, as treatment was continued until either occurred on the combination regimen.

Response evaluation was based on RECIST 1.0 for participants with measurable disease and Gynecologic Cancer Intergroup CA-125 (Rustin) criteria for participants without measurable disease. The registry describes radiologic and serologic assessments every 2 cycles/6 weeks on treatment. These criteria concern disease assessment and progression; they should not be conflated with the duration-based completion definition.

The record reports median treatment duration of 7.5 months (range 0.7-20.7), but that cohort summary does not identify the proportion meeting the endpoint definition. The numerical therapy completion rate and its uncertainty are not reported in the registry record. Consequently, the endpoint's definition is available, but its observed value cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation. A proportion endpoint summarizes the share of an analysis population meeting a defined condition. Here, the condition is completion of at least 3 months/4 cycles of therapy, and the analysis population is described as all treated participants. To interpret an observed proportion, readers would ordinarily need its numerator and denominator, as well as a measure of uncertainty. The registry record does not report the numerical completion result or a confidence interval, so neither the observed proportion nor its precision can be assessed.

What does a confidence interval communicate?

General statistical explanation. A confidence interval expresses uncertainty around an estimated quantity. For a proportion, it gives a range of values compatible with the observed data under the method used. A wider interval generally indicates less precision, while a narrower interval indicates more precision. An interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the statistical procedure and assumptions. The primary endpoint is described with an 80% confidence interval in the registry, but its numerical estimate and interval are not reported in the registry record. The interval's width and implications therefore cannot be evaluated.

How should a single-group result be read?

General statistical explanation. A single-group study measures outcomes in participants receiving the study regimen, without a concurrent randomized control group. A within-group proportion can describe the experience of that cohort. It does not, by itself, estimate what would have happened to similar participants under another strategy. This matters because disease course, participant characteristics, care practices and other factors can influence observed outcomes. A comparison with an external expectation would require assumptions and information not reported in the registry record.

The study has no randomized allocation comparison: the design is described as single-group and allocation is listed as NA. Accordingly, there is no control-arm contrast to interpret. The registry record also does not report adjusted analyses or a detailed statistical analysis plan. No claim about adjustment, model selection or hypothesis testing can be made from the record.

What does the sample-size planning describe?

General statistical explanation. The registry's planning assumptions describe illustrations based on the observed effect, rather than the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect stated as a fraction of the observed effect. Time-to-event planning figures are expressed as total events, using Schoenfeld; other planning figures are expressed as participants per arm. These are planning illustrations, not observed power. The registry does not report a sample-size justification for this single-group study, and a two-arm planning illustration should not be mistaken for the study's actual design or a result from it.

General statistical explanation. A planning sample size depends on assumptions about the effect to detect, variability or event frequency, significance level, power target and analysis method. Changing those assumptions changes the resulting planning requirement. Such a calculation is not an estimate of the probability that the completed study found a real effect, and it cannot repair missing outcome reporting. No planning count or power result for this study is reported in the registry record.

Why do endpoint definitions and assessment schedules matter?

The primary endpoint depends on a threshold of treatment duration, whereas disease progression is evaluated using response criteria. The registry reports serologic and radiologic assessments every 2 cycles/6 weeks on treatment. It describes RECIST 1.0 for measurable disease and CA-125 (Rustin) criteria for non-measurable disease. These rules establish how disease status is assessed, but they do not provide the observed completion proportion. The registry also describes treatment as continuing until progression on the combination regimen or unacceptable toxicity. Thus, endpoint interpretation depends on distinguishing the minimum completion threshold from the criteria governing continued treatment and disease assessment.

General statistical explanation. Over-dispersion is relevant when count or binary data vary more than a statistical model expects. If ignored, uncertainty estimates may be too small, making findings appear more precise than they are. Whether over-dispersion was assessed or relevant to an analysis cannot be determined: no numerical primary result, fitted model or detailed analysis method is reported in the registry record. The endpoint is a proportion, but that alone does not establish which inferential method was used.

The registry lists an 80% confidence interval for the primary endpoint, but does not provide its limits or explain the interval procedure. The analysis record reports no analyses. Without reported analysis details and numerical results, the statistical uncertainty, assumptions and reproducibility of the endpoint estimate cannot be assessed.

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("Bevacizumab Then Cyclophosphamide With Bevacizumab")
n      <- c(20)
events <- c(0)
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  Bevacizumab Then Cyclophosphamide With Bevacizumab  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists therapy completion rate as the primary endpoint and clinical benefit response rate, progression-free survival and overall survival as secondary outcomes. It does not report a detailed statistical analysis plan, a hypothesis-testing strategy, or a procedure for handling multiple outcomes. Whether multiplicity was formally considered is not reported in the registry record. If several outcomes are tested, the chance of at least one apparently notable result can increase; methods for addressing that issue depend on the analysis plan and intended interpretation. No such method can be attributed to this study from the available record.

The record does not report numerical results for the primary endpoint or the listed secondary outcomes. It also does not describe how missing endpoint or follow-up data were handled, whether any participants were excluded from an outcome analysis, or whether sensitivity analyses were performed. These details are not reported in the registry record. The primary-endpoint population is described as all treated participants, but the record does not give a participant-level accounting of endpoint availability or explain how unavailable measurements would enter the calculation.

Missingness can affect interpretation if participants without recorded outcomes differ from those with recorded outcomes. The direction and size of any such effect depend on the missing-data pattern and the analysis assumptions. Those patterns and assumptions cannot be assessed from the registry record. The absence of a reported method should not be read as evidence that no missing data occurred, nor as evidence that a particular method was used.

The study is single-group, so multiplicity and missing-data concerns do not create a randomized comparison that is otherwise absent. Together with the missing outcome estimates and analysis details, they limit assessment of statistical precision and robustness.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (60.0%), cardiac-ischemia (5.0%), obstruction, colon (5.0%), fatigue (5.0%), head/headache (5.0%).

The registry reports adverse-event information for the Bevacizumab Then Cyclophosphamide With Bevacizumab group. Among 20 participants at risk for serious adverse events, 14 were affected; among 20 at risk for other adverse events, 18 were affected. These are separate registry entries. The record does not explain whether the same participants contributed to both categories, so the counts should not be combined or treated as mutually exclusive.

The listed top serious adverse-event terms are hypertension at 60.0%, cardiac-ischemia at 5.0%, obstruction, colon at 5.0%, fatigue at 5.0%, and head/headache at 5.0%. The registry does not provide additional detail in these entries about event timing, severity grading, duration, recurrence, or attribution to treatment. The percentages describe the listed serious terms; they are not a comparison with an untreated or alternative-treatment group.

These figures support a descriptive reading of reported safety events in the study group, not a causal conclusion. The record does not provide a control-group rate, and the serious-event figures alone do not establish whether the regimen caused a particular event. Deaths are not reported in the adverse-event entry.

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

The registry describes a completed phase 2, single-group study of sequential antiangiogenic treatment for recurrent Müllerian malignancies. It defines a primary endpoint that measures whether treated participants reached at least 3 months/4 cycles of therapy, and it reports median treatment duration of 7.5 months (range 0.7-20.7). It also provides selected adverse-event figures. Those details describe the study and its reported measurements.

The record does not report the numerical therapy completion rate, its confidence interval, or numerical results for the listed secondary outcomes. It is therefore not possible to state from the registry record what proportion met the primary endpoint, how precise that estimate was, or what the study observed for clinical benefit response, progression-free survival or overall survival. Median treatment duration is not a substitute for the completion-rate estimate.

The single-group design does not provide a randomized comparison. Even if a within-group outcome estimate were available, it would describe the cohort and would not by itself show what would have occurred under another treatment strategy. The safety entries are also descriptive and do not establish treatment causation or comparative risk.

The study's completion status and its stated goals do not resolve these limitations. A study can be completed while its registry record lacks numerical outcomes or analysis details. The most defensible interpretation is limited to the design, endpoint definition, treatment-duration summary, listed outcomes and reported adverse-event entries. Claims about treatment effectiveness, comparative benefit, or the precision of missing outcome estimates go beyond what the registry record reports.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a treatment-duration endpoint and disease outcomes. The primary endpoint asks whether participants completed a defined minimum course, while the registry separately describes response and progression criteria and lists clinical benefit response, progression-free survival and overall survival as secondary outcomes. These quantities answer different questions and should not be substituted for one another.

The single-group design also shapes what can be learned. It can describe outcomes and safety within the treated cohort, but it does not provide a randomized estimate against a comparator. This distinction is important when interpreting any observed result: a descriptive experience in a cohort is not equivalent to a treatment effect estimated from a controlled comparison.

The record illustrates why an endpoint definition is not enough for statistical interpretation. The completion threshold and analysis population are described, and median treatment duration is reported, but the numerical completion rate and its confidence interval are not. Without the endpoint estimate, readers cannot assess either its magnitude or its precision.

Finally, the safety reporting emphasizes the need to keep event categories and denominators in view. The serious-event and other-event entries are reported separately, and the registry does not establish that the affected participants are distinct across categories. Reading those figures descriptively, without combining counts or inferring causation, preserves what the record supports while avoiding conclusions it cannot establish.

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 principal limitation for interpretation is that the numerical primary endpoint result is not reported in the registry record. Although therapy completion rate is defined and an 80% confidence interval is specified, neither the estimate nor its interval limits are given. The secondary outcomes are named but their numerical results are also not reported. This prevents evaluation of effect magnitude, precision and outcome patterns.

The single-group design has no concurrent control comparison. The study can describe observations in its treatment cohort but cannot, on its own, provide a randomized comparison with another strategy. The registry does not report a detailed statistical analysis plan, sample-size justification, interim analyses, adjusted analyses, or how missing outcome data were handled.

The treatment-duration summary of 7.5 months (range 0.7-20.7) does not determine the proportion reaching the primary endpoint threshold. Likewise, disease-assessment criteria and scheduled assessments do not replace the missing endpoint result. The registry does not provide sufficient participant-level outcome information to assess endpoint availability or the influence of any missing assessments.

The adverse-event entries are descriptive. There is no comparator rate, and the record does not give detail sufficient to assess causal attribution or participant overlap between the serious and other adverse-event categories. These limitations are specific to interpreting this study from the registry record and should constrain conclusions about both outcomes and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies — NCT00856180.
• Registry record last updated 2018-09-10; status last verified 2018-08.
• Results first posted 2016-05-17.
• 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 describes NCT00856180, a completed phase 2, single-group study titled Sequential Angiogenic Blockade for the Treatment of Recurrent Mullerian Malignancies. Enrollment is listed as 20, allocation as NA, and masking as none. The treatment strategy began with bevacizumab and added oral cyclophosphamide after progression through bevacizumab.

The primary endpoint was therapy completion rate, defined as completing at least 3 months/4 cycles of therapy among all treated participants. The record reports a median treatment duration of 7.5 months (range 0.7-20.7), but not the numerical completion rate or its confidence interval. Clinical benefit response rate, progression-free survival and overall survival are listed as secondary outcomes; numerical results are not reported in the registry record.

Safety entries report serious adverse events affecting 14 of 20 at risk and other adverse events affecting 18 of 20 at risk. The record does not provide a randomized comparator or a detailed statistical analysis plan.