Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer (NCT00548418), a non-randomized phase 2 study. The primary outcome is Anti-tumor Activity as Measured by Surviving Progression-free.

2. Clinical Question

The trial also lists overall survival, response measured by RECIST imaging, and laboratory assessments involving gene expression, hypoxia inducible factor 1 and hypoxia-induced gene expression as secondary outcomes. These are related but distinct questions: a response assessment concerns tumor response by imaging criteria, while the primary endpoint concerns remaining progression-free at a specified time. The registry record does not provide results for these outcomes. Consequently, the clinical question can be described from the planned endpoint and regimen, but the posted record does not establish how the observed outcomes compared with any benchmark or alternative treatment.

3. Trial Design

The registry identifies this as a phase II, single-group, non-randomized trial with no masking. The trial is marked completed. Its enrollment is listed as 27; this is a registry enrollment figure, not a reported count for a specific endpoint analysis. The record names Washington University School of Medicine as sponsor and gives a start date of 2007-02 and primary completion date of 2012-12.

Participants were assigned to the listed treatment group receiving cisplatin, topotecan and bevacizumab. Cisplatin was specified at 50 mg/m2 intravenously on day 1 of a 21-day cycle; topotecan at 0.75 mg/m2 intravenously on days 1, 2 and 3; and bevacizumab at 15 mg/kg on day 1. The registry does not report how many cycles participants received, whether doses could be delayed or changed, or what rules governed treatment discontinuation.

Because the design is single group and non-randomized, the main endpoint is an outcome observed among participants treated under the trial regimen. There is no randomized comparator in the record to separate treatment-associated outcomes from the course of disease or other influences. This limits causal interpretation and means that the design should not be read as a direct head-to-head comparison.

The registry lists secondary outcome measures covering overall survival, response assessed by RECIST imaging, and laboratory correlations involving gene expression and hypoxia. Although the record reports five outcome measures, it does not give results for them or describe the analysis population for each. The rationale for the enrollment target, eligibility criteria, follow-up schedule, and analysis plan are not reported in the registry record. These omissions make it difficult to determine how the planned trial questions were operationalized or how representative the enrolled population was.

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

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 Anti-tumor Activity as Measured by Surviving Progression-free, measured over Progression-free survival at 6 months.

The primary endpoint is described as anti-tumor activity measured by the percentage of participants surviving progression-free, with progression-free survival assessed at 6 months. The registry definition starts the period at study entry and ends it at documentation of disease progression, death, or the date of last contact, whichever occurred first. The unit is a percentage of participants.

As a general statistical concept, a fixed-time progression-free percentage expresses the share of a study group meeting the endpoint at a specified point in follow-up. It can be easier to interpret than a measure expressed only as a rate or hazard, provided the estimation method and handling of incomplete follow-up are clear. A time-to-event endpoint also uses the timing of progression or death, not just whether an event was ever recorded. Participants whose event status is not known through the specified time require explicit handling in the analysis.

The registry record does not report the observed percentage, its confidence interval, or the method used to estimate it. It also does not describe how participants without complete follow-up through 6 months were treated analytically. Therefore, the endpoint’s intended meaning is identifiable, but its estimated value and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a percentage endpoint at a fixed follow-up time, while defining progression-free survival using the time from study entry to progression, death or last contact. These details matter because a percentage at a landmark and a time-to-event analysis are related but not interchangeable descriptions. The registry record does not specify the calculation method or give a primary endpoint estimate.

What does a percentage endpoint represent?

As a general statistical explanation, a percentage for a binary outcome is based on classifying participants according to whether they meet a defined condition. The condition is being progression-free at 6 months. To interpret such a percentage, a reader needs to know the numerator, denominator, definition of endpoint status, and how participants without complete follow-up were handled. The record gives the endpoint definition and lists enrollment, but it does not report the number meeting the endpoint or the analysis denominator. Enrollment should not automatically be assumed to equal the analysis denominator.

A fixed-time percentage is intuitive because it refers to a specific point in follow-up. A time-to-event approach can also account for when events happen and, under specified assumptions, use follow-up that ends before the event is observed. These approaches require transparent methods. In this record, the mention of last contact in the endpoint definition does not explain whether participants with no documented progression or death at last contact were censored, excluded, or handled another way. The censoring rules and the estimator are not reported in the registry record.

Why does uncertainty matter?

As a general explanation, a point estimate is an estimate from the observed study data, not a guarantee of the true value in a broader population. A confidence interval communicates sampling uncertainty around an estimate under the method’s assumptions. Its interpretation depends on the analysis and data quality; it does not remove the limitations of a single-group design or account automatically for bias from missing follow-up. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be assessed.

A p-value, when used, evaluates compatibility between data and a specified statistical model or null hypothesis. It does not measure the size or clinical importance of an effect. The record does not report a primary endpoint p-value, and it does not identify a null value or comparison for such a test. Since the trial is single group, any comparison with an external benchmark would need to be described explicitly; none is reported in the registry record.

What does the design imply for comparisons?

The trial is listed as non-randomized and single group, with no masking. In general, random allocation helps balance both known and unknown prognostic factors across treatment groups, while a concurrent comparator permits a direct group contrast. Without those features, a within-study outcome can be described, but causal attribution is more limited. Differences between this group and an external population could reflect population characteristics, care settings, follow-up, or measurement practices as well as treatment. No such external comparison is described in the registry record.

The registry identifies a phase II trial, but it does not report the protocol’s hypotheses, statistical plan, or sample-size justification. The enrollment figure should not be interpreted as evidence that a particular power target was achieved. A planning calculation is different from observed statistical power: planning calculations use assumptions about an effect and variability to illustrate a possible design, whereas observed power is not a substitute for reporting an estimate and its uncertainty.

The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning assumptions, not features of the single-group trial design. The record does not report the observed primary effect needed to assess the stated basis for such an illustration, or the resulting planning figures. Any planning scenario therefore cannot be read as a result from this trial or as evidence about the precision of its observed endpoint.

How should multiple outcomes be considered?

The record lists a primary outcome and secondary outcome measures. As a general statistical issue, examining several outcomes or analyses can increase the chance of obtaining a seemingly notable result by chance if no multiplicity approach is planned. A prespecified hierarchy or adjustment can address some multiplicity concerns, but the registry record does not report a multiplicity plan, analysis hierarchy, or results for the secondary measures. It is not possible to determine from this record how these outcomes were interpreted together.

Finally, statistical methods depend on the population analyzed and the completeness of follow-up. Missing outcome data can affect both the denominator and the estimated percentage, particularly if missingness is related to disease status. General methods can describe or model incomplete follow-up, but each relies on assumptions. The record does not report missing-data handling, analysis-set definitions, or sensitivity analyses. Those omissions prevent an independent assessment of robustness.

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 (Cisplatin, Topotecan, Bevacizumab)")
n      <- c(27)
events <- c(16)
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 (Cisplatin, Topotecan, Bevacizumab)  27  16  59.3  38.8  77.6  40.7  75.5  40.6  75.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary progression-free endpoint and secondary outcomes covering overall survival, RECIST response, gene expression, and hypoxia-related measures. The registry record does not report a multiplicity strategy, such as a hierarchy for interpreting outcomes or an adjustment for multiple statistical tests. It also does not report analysis results for the listed measures. With no reported results or analysis plan, the relationship between the primary and secondary questions cannot be evaluated statistically.

The record lists no analyses. It does not describe whether the primary endpoint was assessed in all enrolled participants, in an eligible or treated population, or in another defined analysis set. Although enrollment is listed as 27, that figure does not establish the denominator used for any outcome.

Missing-data methods are not reported in the registry record. In general, incomplete follow-up can affect the estimate of a fixed-time progression-free percentage, and the direction or size of that effect depends on why follow-up is incomplete and how the analysis handles it. The endpoint definition mentions date of last contact, but does not explain censoring rules, assumptions about censoring, or sensitivity analyses.

The registry also does not report a sample-size justification or a prespecified statistical analysis plan. The stated planning assumptions describe an illustrative two-arm calculation, whereas the trial design is single group. Such planning figures do not define the observed analysis population or replace reporting of the endpoint estimate and its uncertainty.

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: blood clot/dvt (7.4%), back pain (7.4%), esophageal stenosis (3.7%), abdominal pain (3.7%), elevated creatinine (3.7%).

The registry reports serious adverse events for the treatment group: 12 affected participants among 27 at risk. It also lists 27 affected in the other adverse event category among 27 at risk. These are the registry’s reported counts; they do not show how events were distributed across individuals beyond the affected-participant figures.

The serious event terms with listed percentages are Blood clot/DVT, 7.4%; Back pain, 7.4%; Esophageal stenosis, 3.7%; Abdominal pain, 3.7%; Elevated creatinine, 3.7%; and Small bowel obstruction, 3.7%. These percentages should be read as the registry reports them. The record does not explain the calculation method for each term, whether participants could have more than one event, or the time period used for event collection. The terms therefore should not be added together or interpreted as mutually exclusive categories.

The deaths field is not reported in the registry record. These safety figures describe reports within a single treatment group; without a comparator, they do not establish how event frequency differs from another treatment or background risk. The registry record does not provide further detail on event severity grades, duration, outcome, or attribution to treatment.

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

The record establishes that a phase II trial was completed and evaluated a regimen of cisplatin, topotecan and bevacizumab in a single group described as having recurrent or persistent cervical cancer. It identifies progression-free status at 6 months as the primary endpoint and lists several secondary outcomes. This gives a clear outline of the intended clinical questions and the treatment schedule.

The record does not report the observed primary endpoint percentage, confidence interval, or analysis method. It also does not report the listed secondary outcome results. Therefore, the registry information does not establish the magnitude or precision of the observed progression-free outcome, nor does it support a statistical comparison with another regimen or control group.

Even a reported outcome from a single-group trial would need cautious interpretation. As a general principle, an observed outcome can reflect participant characteristics, disease course, follow-up, and other factors as well as treatment. Without randomization and a concurrent comparator, the design cannot on its own distinguish those influences. This is a limitation of what the design can establish, not a conclusion about the regimen’s effect.

The serious adverse event counts and terms describe safety reporting in the study group, but do not provide a comparative safety estimate. The registry does not report the deaths field, event attribution, or the details needed to understand how event categories were assembled. Overall, the record supports a description of trial design, regimen and intended outcomes; it does not supply the outcome evidence required to draw a conclusion about efficacy or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates a central statistical distinction: a clearly defined clinical endpoint is not the same as a reported endpoint result. The registry specifies progression-free status at 6 months and gives a definition involving progression, death or last contact. But without the observed estimate, its denominator, and an uncertainty measure, readers cannot assess the result’s magnitude or precision.

The single-group, non-randomized design also makes the interpretation of any observed outcome different from a randomized comparison. A one-group estimate can describe what happened among participants in that study, but does not itself show what would have happened to comparable participants under another treatment or no treatment. This distinction is important when interpreting uncontrolled clinical evidence.

The record further highlights why analysis details matter for time-to-event outcomes. Rules for incomplete follow-up, endpoint status, and the analysis population shape how an estimate is produced. Those details are not reported in the registry record, so the endpoint definition alone is insufficient to reconstruct or evaluate the analysis.

Finally, the presence of several secondary outcomes raises questions about how outcomes were prioritized and interpreted. A planned multiplicity strategy and complete reporting help readers distinguish confirmatory questions from exploratory ones. The registry does not provide those details or outcome results. Statistically, the record is informative about the intended design and measurement, but incomplete as a report of evidence.

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.

Important details for interpreting this particular trial are not reported in the registry record. The record does not give eligibility criteria beyond the description of recurrent or persistent cervical cancer, so the clinical characteristics of the enrolled group cannot be assessed. It lists enrollment of 27 but does not report participant flow, the number treated, or the analysis population for the primary or secondary outcomes.

The registry provides the planned treatment schedule but not the number of cycles received, dose modifications, treatment discontinuations, or adherence. Follow-up procedures and duration are also not reported. These details would help explain how exposure and outcome ascertainment varied across participants.

The primary endpoint definition mentions progression, death and last contact, but the record does not specify how last contact was handled analytically, how incomplete follow-up was treated, or which estimator was used. No primary endpoint result, uncertainty interval, or analysis output is reported. The registry lists no analyses and does not give a statistical analysis plan, sample-size justification, or multiplicity approach.

The absence of a randomized comparator is a design limitation for causal and comparative interpretation. No external benchmark is described in the registry record. For safety, the record gives affected-participant counts and selected serious event terms, but does not report event attribution, severity grades, timing, or the deaths field. Together, these omissions restrict assessment of both the trial’s outcome estimates and the methods used to obtain them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Topotecan, Cisplatin and Bevacizumab for Recurrent/Persistent Cervical Cancer — NCT00548418.
• Registry record last updated 2014-08-01; status last verified 2014-07.
• Results first posted 2014-07-28.
• 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.

19. Record Summary

The registry describes a completed phase II, non-randomized, single-group trial with no masking, sponsored by Washington University School of Medicine. Enrollment is listed as 27; the study start is 2007-02 and primary completion is 2012-12. The population is described as having recurrent or persistent cervical cancer.

The treatment group received cisplatin, topotecan and bevacizumab on the listed 21-day schedule. The primary outcome was the percentage of participants progression-free at 6 months. Secondary outcomes include overall survival, RECIST response, and laboratory measures of gene expression and hypoxia-related activity.

The registry record does not report the primary or secondary outcome results, analysis populations, missing-data methods, or statistical analysis plan. It lists serious adverse event counts and terms but does not report the deaths field. Because there is no comparator group, the design does not provide a randomized treatment contrast.