This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
CIRCCa was a randomized, double-masked phase 2 trial evaluating carboplatin and paclitaxel with or without cediranib maleate in patients with metastatic or recurrent cervical cancer that cannot be removed by surgery. The registry lists overall progression-free survival as the primary endpoint.
| Feature | CIRCCa |
|---|---|
| Phase | Phase 2 |
| Population | Patients with metastatic or recurrent cervical cancer that cannot be removed by surgery |
| Design | Randomized, double-masked |
| Primary purpose | Treatment |
| Enrollment | 130 |
| Primary endpoint | Overall progression-free survival |
| ClinicalTrials.gov | NCT01229930 |
| Lead sponsor | University of Glasgow |
| Sponsor type | Other |
| Status | Completed |
2. Clinical Question
The central question was whether adding cediranib maleate to carboplatin and paclitaxel affected overall progression-free survival in patients with metastatic or recurrent cervical cancer that cannot be removed by surgery.
Population
Patients with metastatic or recurrent cervical cancer that cannot be removed by surgery.
Intervention
Carboplatin and paclitaxel with cediranib maleate.
Comparator
Carboplatin and paclitaxel without cediranib maleate.
Primary question
Does adding cediranib maleate to carboplatin and paclitaxel change overall progression-free survival?
3. Trial Design
Cediranib-containing regimen
- Carboplatin
- Paclitaxel
- Cediranib maleate
Carboplatin and paclitaxel regimen
- Carboplatin
- Paclitaxel
- Without cediranib maleate
The registry describes the allocation as randomized and the masking as double. It does not report an allocation ratio in the available record.
4. Trial Timeline
Trial start
The CIRCCa trial began in June 2010.
Primary completion
The registry lists December 2012 as the primary completion date.
Registry status
The ClinicalTrials.gov record lists the study status as completed.
5. Primary Endpoint
| Endpoint | Registry definition | Statistical role |
|---|---|---|
| Overall progression-free survival | Overall progression-free survival | Primary endpoint |
The registry identifies overall progression-free survival as the sole registered primary endpoint. The available record does not provide a more detailed endpoint definition, assessment schedule, censoring rule, or analysis specification.
6. Statistical Methodology
The registry establishes the key design features needed to understand the primary comparison: the study was randomized, double-masked, and intended for treatment evaluation. It does not post a statistical analysis plan or formal statistical analyses for the primary endpoint.
Time-to-event analysis
Overall progression-free survival is ordinarily analysed as a time-to-event outcome rather than as a simple proportion. The analysis uses the amount of follow-up available for each participant and accounts for participants who are censored before experiencing the event.
Here, T represents the time from the relevant starting point to the progression-free-survival event. The survival function describes the probability of remaining event-free beyond time t.
Kaplan-Meier estimation
A Kaplan-Meier estimator is commonly used to describe progression-free survival over time. It produces a stepwise estimate of the event-free survival function while retaining information from participants whose observations are censored.
At each event time, di is the number of events and ni is the number of participants at risk immediately before that time.
Comparison between randomized groups
For a randomized two-group time-to-event comparison, a log-rank test is commonly used to compare the survival experience between treatment groups. A Cox proportional-hazards model can additionally summarize the relative event rate through a hazard ratio and its confidence interval.
A hazard ratio compares the instantaneous event rates between two groups under the fitted model. It is not the same as a risk ratio, an absolute risk difference, or a difference in median survival.
These are standard statistical approaches for progression-free survival, but the ClinicalTrials.gov record does not state that a particular Kaplan-Meier, log-rank, or Cox procedure was used for CIRCCa.
7. Planned Analysis
The registry says that overall progression-free survival is the primary endpoint. No formal statistical analyses are posted on ClinicalTrials.gov.
What would normally be measured?
The time-to-event experience of patients assigned to the randomized treatment groups, using progression-free survival as the primary outcome.
How is PFS typically summarized?
Time-to-event studies commonly use Kaplan-Meier estimates to describe event-free survival over time and may report selected survival probabilities and median event times.
How is treatment compared?
A randomized comparison of PFS commonly uses a log-rank test and may use a Cox proportional-hazards model to estimate a hazard ratio with a confidence interval.
What does the registry report?
The record identifies overall progression-free survival as the primary endpoint but does not post formal statistical estimates, confidence intervals, or p-values.
8. Statistical Methods Explained
Why is progression-free survival analysed as a time-to-event endpoint?
Participants can have different lengths of observation, and some may leave observation without experiencing the endpoint. A time-to-event framework can incorporate both the timing of events and right-censored observations instead of treating every participant as if follow-up were identical.
Why use a Kaplan-Meier estimator?
Kaplan-Meier estimation provides a way to describe the probability of remaining free of the event over time while accommodating censoring. The resulting curve can show when events accumulate and how the event-free experience changes during follow-up.
What does a hazard ratio mean in a PFS analysis?
A hazard ratio is a relative comparison of instantaneous event rates under a fitted time-to-event model. A value below 1 would indicate a lower estimated event rate in the numerator group, whereas a value above 1 would indicate a higher estimated event rate. It does not directly state the percentage of patients who avoid progression.
Why is censoring important?
Censoring determines which portion of each participant's follow-up contributes to the analysis. The validity of a survival analysis depends on appropriate definitions of when observations are censored and on assumptions concerning the relationship between censoring and the event process.
What does randomization contribute statistically?
Randomization creates the basis for comparing outcomes between treatment assignments while reducing systematic differences in measured and unmeasured baseline characteristics in expectation. It is therefore central to interpreting a treatment-group comparison causally.
Why does double masking matter?
Masking can reduce the opportunity for knowledge of treatment assignment to influence treatment administration, participant behavior, outcome assessment, or other aspects of trial conduct. The extent to which masking is relevant depends on the endpoint and how it is assessed.
Why are confidence intervals important?
If a hazard ratio and confidence interval were reported, the interval would describe statistical uncertainty around the estimated relative effect under the specified analysis framework. It would not describe the range of effects experienced by individual patients.
9. Interpretation of the Primary Endpoint
The registry identifies overall progression-free survival as the primary endpoint of the randomized CIRCCa comparison. Because the record contains no posted statistical estimates, there is no hazard ratio, confidence interval, p-value, median progression-free survival, or survival probability in the available record from which to characterize the magnitude or precision of the treatment effect.
A complete time-to-event result would typically distinguish the estimated treatment effect from the underlying event-time distributions. For example, a hazard ratio would summarize a relative event-rate comparison, while Kaplan-Meier estimates or median PFS would communicate absolute time-specific or distributional information.
Knowing that a trial was randomized and that PFS was its primary endpoint establishes the design and estimand framework, but it does not establish the direction, magnitude, statistical uncertainty, or clinical relevance of the observed treatment effect.
10. Limitations
- No posted statistical analyses: the ClinicalTrials.gov record used here contains no formal statistical analyses for the primary endpoint.
- Limited endpoint detail: the registry identifies overall progression-free survival but does not provide a detailed endpoint definition, assessment schedule, or censoring specification in the available record.
- No effect estimate: the record does not provide a hazard ratio, confidence interval, p-value, median PFS, or other numerical efficacy result.
- No allocation ratio: the record describes the study as randomized but does not report an allocation ratio in the available trial information.
- No baseline characteristics: the available record does not report a baseline characteristics table by randomized group.
- No subgroup results: the available record does not provide subgroup estimates or interaction analyses.
- No safety results: although laboratory biomarker analysis, pharmacological study, and quality-of-life assessment are listed among the interventions, the available record does not provide serious adverse-event results by arm.
- No detailed analysis plan: the available registry information does not specify the statistical model, hypothesis-testing framework, multiplicity strategy, interim analysis procedure, missing-data method, or stratification factors for the primary endpoint.
11. Why This Trial Matters Statistically
CIRCCa is a useful statistical case study because its registry record combines a randomized treatment comparison with a time-to-event primary endpoint. Even without posted numerical results, the design illustrates several principles that are fundamental to clinical-trial analysis.
| Concept | How it appears in CIRCCa |
|---|---|
| Randomization | The registry describes the allocation as randomized. |
| Masking | The registry describes the study as double-masked. |
| Primary endpoint | Overall progression-free survival. |
| Time-to-event analysis | PFS requires attention to event timing and censoring. |
| Kaplan-Meier estimation | A standard descriptive approach for PFS curves. |
| Hazard ratio | A standard model-based summary of relative event rates for time-to-event outcomes. |
| Log-rank testing | A commonly used method for comparing randomized time-to-event distributions. |
| Censoring | Participants without an observed event can contribute follow-up through their censoring time. |
| Analysis transparency | The absence of posted statistical analyses limits interpretation of the observed treatment effect. |
12. Sources
- ClinicalTrials.gov: CIRCCa (NCT01229930).
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13. Record Summary
CIRCCa was a completed, randomized, double-masked phase 2 trial enrolling 130 patients with metastatic or recurrent cervical cancer that cannot be removed by surgery. The intervention comparison was carboplatin and paclitaxel with or without cediranib maleate, and the registry identifies overall progression-free survival as the primary endpoint. The record provides the essential trial design and timing information but does not post formal statistical analyses or numerical results for the primary endpoint. Statistically, the trial therefore provides a clear framework for understanding randomized PFS analysis while leaving the observed treatment effect unspecified in the registry record.