Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma (NCT00815308), a na phase 2 study. The primary outcome is Number of Participants With Overall Response Rate (RR).

2. Clinical Question

The study's stated purpose was to determine whether cetuximab combined with paclitaxel, cisplatin, and radiation could improve clinical outcomes in locally advanced ESCC. That wording describes the question motivating the study; it is not, by itself, evidence that outcomes improved. Without a control group, the record cannot provide a randomized estimate of how outcomes under the combination compare with outcomes under another treatment.

The study also listed toxicity, overall survival at 1 Year and 3 Year, progression-free survival, and K-ras gene mutation among its secondary outcomes. Numerical results for those outcomes are not reported in the registry record. The available information therefore describes the intended clinical question and endpoint definitions more fully than it describes the observed clinical outcomes.

3. Trial Design

This was a Phase 2, open-label, single-group study sponsored by Shandong Cancer Hospital and Institute. The record gives a start date of 2009-01, a primary completion date of 2010-07, and a status of COMPLETED. Enrollment is listed as 55. The allocation is recorded as NA, masking as NONE, and the study model as SINGLE GROUP.

All participants were assigned to the listed combination of cetuximab, paclitaxel, cisplatin, and radiation; there is no separate control arm in the registry record. As a result, the design does not support a like-for-like comparison between the combination and a concurrent alternative. Changes over time or comparisons with results from other settings would not have the protection against differences between groups that random assignment can provide.

The intervention description specifies a cetuximab loading dose of 400 mg/m² on Day 1 in Week 1, followed by 250 mg/m² on Day 1 every week for Weeks 2-8. Paclitaxel was listed at 45 mg/m² and cisplatin at 20 mg/m² on Day 1 every week for Weeks 2-8. Radiation was listed as 59.4 Gy, 1.8 Gy/33 fractions. Other treatment-delivery details, including any treatment modifications or completion information, are not reported in the registry record.

The open-label designation means masking was not used, according to the registry. In general, lack of masking can matter when outcomes involve judgment, follow-up decisions, or reporting of symptoms. The primary response endpoint used imaging and examination criteria, but the record does not describe whether response assessments were independently reviewed or blinded.

Other design information that could help interpret the study, including eligibility criteria, participant characteristics, the planned sample size, and details of follow-up, is not reported in the registry record. The single-group structure and absence of posted endpoint estimates are especially important when judging what can be concluded from the 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:

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 Number of Participants With Overall Response Rate (RR), measured over 1 to 3 month after therapy.

The primary endpoint was the number of participants with an overall response rate, with the unit recorded as participants. The registry defines an overall response as a complete response (CR) or partial response (PR), assessed 1 to 3 month after therapy. A complete response required no target lesion at follow-up computed tomography scan and barium swallow examination 3-6 weeks after completion of chemo-radiation. A partial response required at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum of diameters as the reference.

In general, response endpoints are used to describe whether measurable disease meets prespecified criteria for reduction or disappearance over a stated assessment period. Combining complete and partial responses into an overall response measure can provide a concise summary of tumor response, while the separate criteria retain different thresholds of change. The endpoint is not the same as a measure of how long participants live or remain free of progression; those outcomes were listed separately among the secondary outcomes.

The registry gives the response definition but does not report a numerical response count or proportion in the record. It also does not report an uncertainty estimate, such as a confidence interval, for the primary endpoint. Thus, the endpoint's definition can be described, but the magnitude and precision of the observed response result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the study as Phase 2, open-label, and single-group, with allocation recorded as NA and masking as NONE. Those design labels determine the kinds of statistical claims that can be supported. The study can describe outcomes observed in the treated group, but it has no concurrent control group for a direct treatment comparison. The registry record does not report a statistical analysis plan, a model for the primary outcome, or a planned sample-size justification.

What does a single-group design estimate?

In general, a single-group study can estimate the frequency of an outcome among participants observed under the study treatment, if the outcome data and analysis are reported. Such a frequency describes that group in that study setting. It does not, on its own, estimate what would have happened to those participants under a different treatment. A comparative treatment effect requires a comparison, and the record identifies no randomized comparison or like-for-like control group.

This distinction matters even when an outcome definition is precise. The registry sets out criteria for complete and partial response, but it does not report how many participants met them. A clear endpoint definition helps specify what is being counted; it cannot substitute for the count, an estimate of uncertainty, or a comparison group.

How should the response endpoint be understood?

Overall response combines complete response and partial response, as defined in the registry. In general, a binary endpoint classifies each assessed participant according to whether a specified event or criterion occurred. Counts and proportions can summarize such an endpoint, but the registry record does not report the primary response count or a response proportion. The stated unit is participants, and the assessment timeframe is 1 to 3 month after therapy.

In general, uncertainty intervals around a proportion help show how much the estimate might vary because of sampling variability. An interval's interpretation depends on the analysis method and assumptions. No interval or method for the primary response endpoint is reported in the registry record, so statistical precision cannot be assessed. No p-value for that endpoint is reported either.

What does the safety information count?

The safety record presents participants with serious and other adverse events as counts in the treatment group. In general, event counts and the number of participants at risk can describe how frequently reported events occurred during the observed study period. These summaries do not by themselves show whether the events were caused by treatment, nor do they establish comparative risk without a control group. The registry does not report a statistical comparison for safety.

Over-dispersion is a general statistical issue that arises when variability in counts is greater than a simple model expects. It can affect standard errors and confidence intervals in analyses of count outcomes. The registry record does not identify a count model, an over-dispersion assessment, or an analysis that would require such a model. Therefore, this concept is relevant as general statistical context, not as a claim about an analysis used in this study.

What can be learned from the survival outcomes?

The listed secondary outcomes include overall survival at 1 Year and 3 Year and progression-free survival. In general, time-to-event outcomes concern the time until a defined event, and analyses may need to account for participants whose event has not been observed by the end of follow-up. Methods such as survival curves or time-to-event models can address that structure under specified assumptions. The registry record does not provide outcome estimates, event counts, follow-up distributions, censoring details, or the statistical methods used for these outcomes. No survival result should be inferred from their appearance in the outcome list.

The sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Time-to-event illustrations use the total number of events; other illustrations use participants per arm. These assumptions are not a report of the trial's own design or a record of observed power. In general, planning calculations estimate what a future study might require under chosen assumptions; they do not establish the probability that a completed study has detected a real effect. Numerical planning outputs and the trial's own sample-size justification are not reported in the registry record.

What is missing from the analysis record?

The record lists six outcome measures and zero analyses. It does not report a statistical analysis plan, model specifications, adjustment methods, confidence intervals, or p-values for the clinical outcomes. The absence of these details prevents assessment of how estimates were calculated and whether planned analyses differed from reported analyses. It should not be interpreted as proof that no statistical work took place outside the registry record. Rather, it marks what cannot be verified from the registered information.

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("Cetuximab, Concurrent Chemo-radiotherapy")
n      <- c(55)
events <- c(44)
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  Cetuximab, Concurrent Chemo-radiotherapy  55  44  80.0  67.0  89.6  67.6  88.4  67.6  88.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures: the primary overall response endpoint and secondary outcomes covering toxicity, overall survival at 1 Year and 3 Year, progression-free survival, and K-ras gene mutation. When a study examines multiple outcomes, general statistical practice considers multiplicity: the more inferences made, the greater the chance that at least one result may appear noteworthy by chance if each is assessed independently. Methods to address multiplicity depend on the study objectives and analysis plan.

A multiplicity adjustment or testing hierarchy is not reported in the registry record. Nor does the record report which outcomes were included in any formal analysis; it lists zero analyses. The presence of multiple outcome measures alone does not show that a particular adjustment was required or used. Without a stated analysis plan and numerical results, the inferential consequences cannot be evaluated.

Missing-data methods and analysis populations are also not reported in the registry record. In general, missing outcome assessments can affect estimates when participants with and without observed outcomes differ. Appropriate handling depends on why data are missing, how much is missing, and the endpoint. The record does not give missingness counts, reasons for missing assessments, or an imputation or sensitivity-analysis approach.

The registry enrollment is 55, but the number included in each outcome analysis is not reported. It is therefore not possible to determine from the record whether all enrolled participants contributed to each endpoint, how exclusions were handled, or what analysis population was used. These omissions limit evaluation of the completeness and robustness of the reported clinical findings, which are themselves not numerically reported for the primary endpoint.

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 1.81% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: esophago-tracheal fistula (1.8%), pneumonia (1.8%).

The registry reports serious adverse events for the single treatment group: 2 participants were affected among 55 at risk. It reports other adverse events for 38 participants among 55 at risk. The top serious event terms are esophago-tracheal fistula at 1.8% and Pneumonia at 1.8%. These are registry-reported counts and terms, not a comparison with another treatment group.

In general, adverse-event summaries describe what was recorded under the study's reporting rules during the observed period. A count does not by itself establish that an event was caused by treatment. The registry record does not give event-level timing, severity beyond the serious-event classification, relatedness assessments, or details about whether participants could have more than one event. The listed serious event terms should therefore not be treated as a complete account of all safety outcomes.

The record gives no death count for this safety summary. It also does not report a statistical comparison of safety rates. Because the study has a single group, these figures describe reported events in that group; they cannot establish how the event frequency compares with an alternative treatment or control condition. The counts should be read alongside these limitations, rather than as a comparative estimate of harm.

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

The record establishes that a completed Phase 2 study examined cetuximab with paclitaxel, cisplatin, and radiation in locally advanced ESCC. It defines an overall response endpoint, lists secondary outcomes, and reports some adverse-event counts. This information is useful for understanding the study's clinical question and what outcomes the registry tracked.

It does not establish the size or precision of the primary response outcome. Although the endpoint definition is detailed, the registry record does not report a numerical response result, a confidence interval, or a statistical test. The stated aim of evaluating whether outcomes improve is not itself a finding. No conclusion about the amount of response, survival, or progression-free survival can be drawn from the outcome labels alone.

The design also does not estimate a treatment effect relative to a concurrent alternative. In general, outcomes in a single treatment group can reflect the treatment and other influences, including participant characteristics and the course of disease. Without a randomized comparison, those influences cannot be separated through a direct between-group contrast. The serious adverse-event counts likewise have no comparator in this record.

The safety figures describe reported events in the study group, but do not prove causation or provide a comparative safety estimate. The record does not include enough detail to assess the completeness of adverse-event ascertainment, event timing, or relatedness. Its safety information is descriptive rather than a basis for comparing treatment risks.

Accordingly, the statistical meaning of this record is primarily descriptive: it documents the study structure, treatment regimen, endpoint definitions, and selected safety counts. It does not provide the numerical primary result or analyses needed to judge statistical uncertainty. The registry information alone therefore cannot support a claim that the treatment did or did not improve clinical outcomes.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry specifies how complete and partial response were defined, including imaging criteria and the assessment timeframe. Yet without a numerical response result, readers cannot assess the observed response frequency or its precision. A definition clarifies the target of measurement; it does not provide evidence about the outcome.

The single-group design is another important statistical feature. It can describe outcomes among participants receiving the regimen, but it does not furnish a concurrent comparison for estimating relative effects. This distinction is fundamental when the stated clinical question concerns whether treatment improves outcomes. A descriptive study result and a causal comparison answer different questions.

The record also demonstrates the difference between an outcome list and an analysis report. Overall survival, progression-free survival, toxicity, and K-ras gene mutation appear among the secondary outcomes, but their numerical results and analysis methods are not reported in the registry record. Registering an outcome does not disclose its result or the uncertainty surrounding it.

Finally, safety counts are informative only within their reporting context. The serious and other event counts describe the study group, while the absence of a control group limits comparative interpretation. Together, these features show why readers need both transparent outcome reporting and a design suited to the intended comparison before drawing statistical conclusions.

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 limitations specific to this record constrain interpretation. It describes a single-group study with no randomized comparison, so it cannot directly estimate outcomes relative to a concurrent control or alternative treatment. The open-label designation and absence of masking are recorded, but the registry does not explain how response assessments were reviewed or whether assessment procedures could have been influenced by knowledge of treatment.

The numerical result for the primary response endpoint is not reported in the registry record. Although the response criteria and timeframe are described, there is no reported response count, proportion, confidence interval, or p-value. Numerical results for the listed secondary outcomes are also not reported. The record lists six outcome measures and zero analyses, leaving the analysis methods and estimates unavailable for assessment.

Information about participant eligibility and baseline characteristics is not reported in the registry record, limiting assessment of who the findings would describe. The record also does not describe missing outcome data, analysis populations, follow-up completeness, or how participants who did not complete treatment were handled. These details matter for evaluating whether reported outcomes represent the enrolled group fairly.

The safety summary provides counts and two serious-event terms but does not report event timing, relatedness, or a comparative analysis. A death count is not reported. The registry also does not provide a statistical analysis plan, a sample-size justification for this trial, or enough information to assess multiplicity and outcome-specific analysis choices. These limitations concern the information available in the registry record; they do not establish what was or was not done outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Erbitux Combined With Chemo-radiotherapy in Esophageal Squamous Cell Carcinoma — NCT00815308.
• Registry record last updated 2011-02-08; status last verified 2009-07.
• Results first posted 2011-02-03.
• 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 record describes NCT00815308, a completed Phase 2, open-label, single-group study sponsored by Shandong Cancer Hospital and Institute. The study evaluated cetuximab with paclitaxel, cisplatin, and radiation for locally advanced esophageal squamous cell carcinoma. Enrollment was 55; the record lists a start date of 2009-01 and primary completion date of 2010-07.

The primary endpoint was the number of participants with overall response, defined as complete or partial response, with an assessment timeframe of 1 to 3 month after therapy. The registry gives response criteria but does not report a numerical primary result. Secondary outcomes include toxicity, overall survival at 1 Year and 3 Year, progression-free survival, and K-ras gene mutation; numerical results for these outcomes are not reported in the registry record.

Safety information lists 2 participants with serious adverse events and 38 with other adverse events, among 55 at risk. Esophago-tracheal fistula and Pneumonia are each listed at 1.8% as top serious event terms. With no control group, these figures are descriptive, not comparative.