Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery (NCT00290615), a non-randomized phase 2 study. The primary outcome is Response Rate (Percentage of Participants With Partial or Complete Response).

2. Clinical Question

3. Trial Design

This is a phase II study of capecitabine, oxaliplatin, bevacizumab, and cetuximab in metastatic colorectal cancer. The registry record describes the intended population as patients with metastatic or recurrent colorectal cancer that could not be removed by surgery. It lists the study as completed, non-randomized, unmasked, and single-group. The listed enrollment is 30, but that figure does not establish how many participants received treatment or entered the primary-endpoint analysis.

The arm description gives capecitabine as oral administration of 850 mg/m2 every 12 hours on days 1–14. Oxaliplatin is described as intravenous administration of 130 mg/m2 over 2 hours on day 1 of a cycle, and bevacizumab as intravenous administration of 7.5 mg/kg over 30–90 minutes on day 1 of a cycle. The record gives cetuximab at an initial dose of 400 mg/m2 over 120 minutes; its full schedule is not reported in the registry record.

Restaging scans were scheduled every 9 weeks from study-drug initiation until disease progression, with assessment described as extending up to 24 months. The primary endpoint is response rate, defined as the percentage of participants with partial or complete response. Safety and tolerability, progression-free survival, and overall survival are listed as secondary outcomes, but their results are not reported in the registry record.

Because the study has one group and no randomized comparator, its design can describe outcomes among participants treated in the study but cannot provide a randomized estimate of how outcomes differ from another treatment. The record does not report the rationale for the enrollment target, the full statistical analysis plan, or details of treatment assignment beyond identifying the study as non-randomized.

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: All subjects who received restaging scans were analyzed.

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 Response Rate (Percentage of Participants With Partial or Complete Response), measured over After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months..

The primary endpoint is the percentage of participants with a partial or complete response. In this context, response is based on disease assessment using RECIST v.1.0. The record defines complete response as disappearance of all target lesions. It defines partial response as at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference. The registry description includes a typographical inconsistency in one label, but the response-rate title explicitly identifies partial or complete response as the endpoint.

Restaging scans occurred every 9 weeks from study-drug initiation until disease progression. The endpoint timeframe is described as assessment after all subjects were evaluated for restaging, up to 24 months. The primary-endpoint population is stated to include all subjects who received restaging scans. The count in that population, the number with each response category, the response-rate estimate, and the stated 95% confidence interval are not reported in the registry record.

As a general statistical concept, response rate condenses an individual participant outcome into a proportion: whether a participant met the stated response definition. This can provide a direct description of tumor response under the study’s assessment criteria. It does not, by itself, describe how long a response lasts or establish that the regimen caused the observed responses. Those questions require information beyond the endpoint definition, including the actual results and an appropriate comparative design.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response classification at the participant level: a participant either met the definition of partial or complete response or did not. The endpoint is expressed as a percentage of participants with response. The record states that the primary-endpoint population consists of all subjects who received restaging scans. It does not state how many participants were in that population, how many had each response classification, or the resulting response estimate.

What does the confidence interval describe?

The endpoint metadata names a 95% confidence interval as the dispersion measure. As a general statistical explanation, a confidence interval communicates the uncertainty associated with an estimated quantity under a specified statistical method. It is not a guarantee that the true value lies within a particular interval, and it does not measure whether the observed response was caused by treatment. Its width depends in part on the amount of information available and on the method’s assumptions. The registry record does not give the interval limits or specify the calculation method, so those aspects cannot be assessed.

For a binary proportion, statistical uncertainty is often affected by the number of observations and by how responses are distributed across participants. This is general context, not a claim about the calculation used in this study. The registry record does not report whether the confidence interval used a particular approximation, an exact method, or another approach. It also does not report adjustments for other variables. No method beyond the named 95% confidence interval should be attributed to the study from this record.

How were responses defined?

The record says that disease assessment was performed and recorded according to RECIST v.1.0. Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking the baseline sum as the reference. Stable disease is defined as neither sufficient shrinkage for partial response nor sufficient increase for progressive disease, using the smallest sum since treatment started as the reference. Progressive disease is defined as at least a 20% increase from the smallest recorded sum since treatment started or the appearance of one or more new lesions.

These categories depend on lesion measurements and the reference value specified for each comparison. The timing of assessment also matters: scans were scheduled every 9 weeks from initiation of study drug until disease progression. The endpoint timeframe states that restaging assessment was conducted up to 24 months. The record does not report adherence to the schedule, missing scans, independent review procedures, or how an assessment that could not be classified was handled.

What does the design permit?

As a general statistical principle, a single-group study can estimate an outcome observed in its enrolled and assessed population, subject to its measurement and analysis methods. It does not create a concurrent randomized comparison. In a non-randomized, unmasked, single-group study, differences from an external benchmark or other study would not be protected by random assignment from differences in patient mix, assessment, follow-up, or other conditions. The registry record does not identify an external comparator or report a comparative effect estimate.

The record lists the study as phase II and completed, with enrollment of 30. Enrollment is not interchangeable with the number analyzed for response, because the stated endpoint population is participants who received restaging scans. The analyzed count and the handling of participants without restaging scans are not reported in the registry record. The record also does not report the sample-size rationale, planned precision, power calculation, or statistical stopping rules.

What cannot be inferred from the posted analysis information?

The registry record lists six outcome measures and no analyses. It names safety and tolerability, progression-free survival, and overall survival as secondary outcomes, but does not provide their results or analysis methods. No adjustment strategy, covariate model, subgroup method, interim analysis, or multiplicity procedure is reported. These omissions do not establish that a method was or was not used outside the registry record; they mean the record does not document it.

General statistical interpretation also distinguishes estimation from testing. An estimate describes a quantity, while a hypothesis test evaluates data against a specified null hypothesis under stated assumptions. The registry record does not report a test for the primary endpoint or a p-value. A response percentage, if reported, would still be descriptive evidence from this single-group study; it would not alone demonstrate a comparative treatment effect.

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("Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab")
n      <- c(30)
events <- c(13)
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  Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab  30  13  43.3  25.5  62.6  27.4  60.8  27.3  60.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies response rate as the primary endpoint and lists safety and tolerability, progression-free survival, and overall survival as secondary outcomes. It also lists six outcome measures, while no analyses are reported in the registry record. The record does not specify how many hypotheses were planned, whether any outcomes were designated as confirmatory, or whether a multiplicity adjustment was planned or performed. A procedure for controlling false-positive findings should not be assumed from the outcome list alone.

As a general statistical concept, multiplicity arises when several outcomes, comparisons, or analyses are considered. If each is interpreted as an independent opportunity for a positive finding, the chance of at least one false-positive result can increase. Methods for addressing this depend on the prespecified questions and analysis plan. The registry record does not report such a plan or any multiplicity-adjusted results.

The primary-endpoint population is described as all subjects who received restaging scans. The record does not report the number who received scans, the number omitted from that analysis, reasons for missing assessments, or how missing response data were handled. It therefore does not establish whether the analysis included all enrolled participants, all treated participants, or another set beyond the stated scan-based population. The enrollment listed as 30 should not be treated as the analyzed denominator.

As a general matter, missing outcome assessments can affect an estimated response proportion if participants with missing data differ in their outcomes from those assessed. Statistical approaches may make different assumptions about such participants, but the record does not report an approach or sensitivity analysis. The primary endpoint’s confidence interval is named, yet its value and calculation method are not reported. These gaps limit assessment of both the precision of the estimate and the robustness of the analysis.

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: diarrhea (20.0%), cerebrovascular accident (6.7%), bowel obstruction (6.7%), death (6.7%), dehydration (3.3%).

The registry record reports safety-event counts for the single listed treatment group. It gives 30 as at risk for serious adverse events and 10 as affected. For other adverse events, it gives 30 as at risk and 30 as affected. These are separate summaries; the record does not provide enough detail to infer severity, timing, or participant-level overlap across event categories.

The listed leading serious-event terms are diarrhea at 20.0%, cerebrovascular accident at 6.7%, bowel obstruction at 6.7%, death at 6.7%, dehydration at 3.3%, and dyspnea at 3.3%. Event terms can overlap within participants, so their percentages should not be added to form a total. The record’s deaths field is not populated, while Death appears among the serious-event terms. Those entries do not establish the circumstances or cause of any death.

As a general statistical caution, an adverse event occurring during a study is not, by itself, evidence that treatment caused it. The registry record does not report event-level attribution, timing, duration, or detailed definitions for these summaries. The single-group design also does not provide a randomized safety comparison. The figures describe the posted safety record and should not be read as comparative risk estimates.

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

The study record describes a phase II investigation of a four-drug regimen for patients with metastatic or recurrent colorectal cancer that could not be removed by surgery. It specifies a primary endpoint based on the percentage of participants with partial or complete response under RECIST v.1.0. It also defines the assessment schedule and names a 95% confidence interval as the endpoint’s dispersion measure. These details establish what the endpoint was intended to capture, but they do not supply the observed response result.

The registry record does not report a response count, response percentage, confidence-interval limits, or number analyzed for the primary endpoint. As a result, it is not possible to describe the magnitude or precision of the observed response rate from the posted record. The listed enrollment of 30 is not a substitute for the endpoint denominator, which is defined as subjects who received restaging scans.

Even if a single-group response estimate were available, its meaning would be descriptive: it would summarize responses observed in that study population under the stated assessment process. The non-randomized, single-group design does not provide a randomized comparison with another treatment. A response estimate alone would not establish what outcomes would have been under a different treatment or show that the regimen caused the responses.

The registry record lists safety and tolerability, progression-free survival, and overall survival as secondary outcomes. It gives some adverse-event summaries, but the results for the named survival outcomes are not reported in the registry record. The presence of an outcome in a registry entry is not equivalent to a reported estimate, and no conclusion about those outcomes can be drawn from their names alone.

General statistical interpretation requires keeping the outcome definition, observed estimate, uncertainty, analysis population, and study design distinct. Here, the outcome definition and design are described, but key result and analysis details are not. The posted information therefore supports a description of the research question and selected safety figures, not a quantitative conclusion about response or a comparative treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why an endpoint definition and a result are different kinds of information. The registry record carefully identifies response rate as the primary endpoint, describes the RECIST v.1.0 categories, and states when restaging scans were scheduled. But it does not report the response estimate, confidence interval, or analyzed population size. Without those results, the endpoint cannot be evaluated quantitatively from the registry record.

The design also matters to interpretation. The study is listed as non-randomized and single-group, with no masking. Such a design can describe outcomes in the treated group, but it does not supply a concurrent randomized control for estimating a treatment contrast. This distinction is important whenever a reader encounters an outcome such as response rate: the measure may be clinically recognizable, while the design still limits what can be attributed to the regimen.

The registry record also illustrates the importance of denominator clarity. Enrollment is listed as 30, while the primary-endpoint population is defined by receipt of restaging scans. Those are not necessarily the same population, and the record does not give the analyzed count. Reporting the number assessed and the handling of missing assessments would help readers understand the basis and precision of an endpoint estimate.

Finally, outcome lists and safety summaries should be read separately from efficacy results. Secondary outcomes are named without reported estimates, and serious adverse-event terms are listed without enough detail to establish causality or comparative risks. These features make transparent reporting of analysis populations, missing-data handling, statistical methods, and endpoint results central to responsible interpretation.

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 trial-specific limitations follow directly from the registry record. First, the study is non-randomized and single-group, so it has no concurrent randomized comparator. Any outcome estimate would describe the study group rather than provide a randomized treatment contrast. The record also identifies masking as none, so it does not describe blinded outcome assessment.

Second, the primary endpoint result is not reported in the registry record. The record names a 95% confidence interval but gives neither its limits nor the response estimate. It also does not report the number of participants who received restaging scans, despite defining that group as the primary-endpoint population. The listed enrollment of 30 cannot fill this gap.

Third, assessment and analysis details are incomplete. Scans are described as occurring every 9 weeks until disease progression, with assessment up to 24 months, but the record does not report missing scans, deviations from the schedule, or how incomplete assessments were handled. It does not specify the confidence-interval calculation method, a statistical analysis plan, or a multiplicity procedure. The number of outcome measures is listed as six, and no analyses are reported.

Fourth, the arm description gives only an initial cetuximab dose and does not report its full schedule. The registry record lists secondary outcomes but does not report their results. Safety summaries include event counts and selected serious-event terms, but do not provide event-level timing, attribution, or circumstances. These gaps limit detailed assessment of both efficacy and safety from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery — NCT00290615.
• Registry record last updated 2013-05-07; status last verified 2013-03.
• Results first posted 2013-05-07.
• 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 II study is listed as non-randomized, unmasked, and single-group, with enrollment of 30. It investigated capecitabine, oxaliplatin, bevacizumab, and cetuximab for metastatic or recurrent colorectal cancer that could not be removed by surgery.

The primary endpoint was the percentage of participants with partial or complete response under RECIST v.1.0. Restaging scans were scheduled every 9 weeks, and the endpoint timeframe extends up to 24 months. The primary-endpoint population is described as subjects who received restaging scans.

The registry record does not report the primary response estimate, its confidence interval, or the analyzed population size. It lists safety and tolerability, progression-free survival, and overall survival as secondary outcomes, without reporting their results. Selected adverse-event figures are listed, but the record does not establish comparative risks or event causality.