S0415 Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for S0415 Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer (NCT00096031), a na phase 2 study. The primary outcome is Overall Survival at 6 Months.

2. Clinical Question

3. Trial Design

This was a phase II study of cetuximab in patients with metastatic esophageal cancer or gastroesophageal junction cancer. The official title describes the treatment as second-line therapy. The registry records a single-group model, allocation listed as NA, and no masking. Those design details mean the registry does not describe a randomized comparison between cetuximab and another treatment.

The enrollment was 63. The record lists SWOG Cancer Research Network as the sponsor, a start date of 2004-10, primary completion in 2008-01, and a completed status. These dates and status describe the study record; they do not provide information about individual participants’ follow-up or the timing at which outcome data were analyzed.

The intervention was cetuximab, classified as biological. The dose schedule is 250 mg/m^2 on days 1, 8, 15, and 22 of every 28-day cycle. The brief summary gives a biological rationale involving blocking enzymes necessary for tumor-cell growth, but the registry does not provide enough information to assess that mechanism from clinical outcomes.

Overall survival at 6 months is the primary outcome. Time to Treatment Failure and Time to Progression are listed as secondary outcomes. The registry record does not report the numerical primary outcome, numerical secondary outcome results, or their uncertainty estimates. It also does not report the study's statistical analysis plan, eligibility criteria, or the rationale used to determine enrollment. Consequently, the design can be described, but the strength and precision of the clinical outcome evidence cannot be evaluated from the registry results presented.

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 Overall Survival at 6 Months, measured over every 3 weeks while on treatment, then every 3 months.

Overall survival at 6 months is the primary endpoint. The registry defines time to death as the interval from registration to death from any cause, and describes the result in terms of the percentage of participants. A fixed-time survival endpoint asks what proportion of the study population is alive at a specified time point. It offers a clinically interpretable snapshot of survival, while the underlying event definition includes death from any cause rather than a specified cause.

The registry lists a 95% confidence interval as the measure of dispersion. In general, a confidence interval communicates the uncertainty around an estimate: a narrower interval indicates greater precision, while a wider interval indicates less precision. The estimate and interval are not reported in the registry record, so neither the observed survival percentage nor its precision can be assessed.

The stated timeframe for outcome assessment is every 3 weeks while on treatment, then every 3 months. The record does not explain how the 6-month endpoint was calculated, how participants with incomplete follow-up were handled, or what analysis population was used. Such details can affect interpretation of a fixed-time survival estimate, particularly when follow-up differs among participants. The endpoint is therefore identifiable, but its calculation and numerical result are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is listed as single group, with allocation NA and masking none. In a single-group study, participants receive the listed intervention and outcomes are observed within that group. General statistical interpretation differs from a randomized comparison: there is no concurrently assigned control group in the registry record against which to estimate a treatment contrast. An outcome observed after treatment can describe the study group, but the design alone does not establish what would have happened to similar participants under another treatment or no study treatment.

What does the primary endpoint estimate?

The primary endpoint is overall survival at 6 months, expressed as a percentage of participants. In general, a fixed-time survival estimate represents the share of a defined analysis population who are alive at the stated time point. The record defines time to death from registration to death from any cause. It lists a 95% confidence interval, which is a way of expressing the statistical uncertainty surrounding an estimate. The estimate and interval themselves are not reported in the registry record, so their magnitude and precision cannot be reviewed.

Survival outcomes can involve differing follow-up times and incomplete observation. General methods for time-to-event data can account for the fact that some participants may not have a recorded event by the end of observation, but the registry does not state which method was used for the 6-month result. It also does not describe censoring rules, the handling of withdrawals, or the analysis population. None of these procedures should be inferred from the endpoint name alone.

How should the secondary outcomes be read?

Time to Treatment Failure and Time to Progression are listed as secondary outcomes. In general, time-to-event outcomes measure the time from a defined starting point until a specified event. Their interpretation depends on the exact event definition, the time origin, follow-up rules, and the treatment of participants who do not experience the event during observation. Those definitions and the numerical results are not reported in the registry record. It is therefore not possible to determine from the record how these outcomes were operationalized or estimated.

What does the record say about statistical analyses?

The registry lists zero analyses. It identifies the primary outcome and its stated confidence interval, but does not report a statistical analysis plan, a statistical test, an estimation method, or adjustment variables. A confidence interval is useful only when the estimate and the method supporting it are available; listing the interval type does not supply the interval itself. The record also does not report interim analyses or a sample-size justification. These details are not reported in the registry record, and should not be assumed.

A separate planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. This is a general planning setup, not the trial's single-group allocation, and it is not evidence that the trial used that design or analysis. The description also distinguishes total event counts for time-to-event planning from participants per arm for other outcomes. Such planning outputs, where presented, are illustrations and not observed power or trial findings. The registry does not report the trial's own sample-size assumptions or justification.

Why do uncertainty and dispersion matter?

Outcome estimates are subject to sampling variability. In general, a confidence interval helps readers judge how precisely the data estimate an outcome, while a point estimate alone can conceal substantial uncertainty. For proportions, the amount of information depends in part on how many participants contribute usable outcome data and how common the event is. The registry does not provide the primary estimate, confidence limits, or analysis denominator, so this precision cannot be evaluated.

For event counts, over-dispersion is a general concern when the variability in observed counts exceeds what a simple model assumes. This matters because methods that underestimate variability can make uncertainty appear smaller than it is. The record does not provide a count-based primary outcome or an analysis model that would permit assessment of over-dispersion. This concept is therefore relevant as general statistical context, not as a claim about an analysis performed in this trial.

Multiplicity concerns arise when several outcomes or analyses are considered, because repeated statistical testing can increase the chance of a chance-positive finding. The registry lists a primary outcome and two secondary outcomes, but does not report a multiplicity strategy or the results of inferential tests. Without those details, the secondary outcomes cannot be used to reconstruct the primary analysis or to establish how the investigators interpreted multiple outcomes.

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")
n      <- c(55)
events <- c(20)
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  55  20  36.4  23.8  50.4  24.9  49.6  24.9  49.6

11. Multiplicity, Missing Data and Analysis Populations

The registry names one primary outcome, overall survival at 6 months, and two secondary outcomes: Time to Treatment Failure and Time to Progression. It does not report a plan for handling multiplicity. In general, multiplicity arises when several outcomes, time points, or statistical tests are assessed. Without a stated strategy, readers cannot tell whether the analyses were treated as independent descriptive outcomes or whether any adjustment to statistical inference was planned. No multiplicity adjustment should be assumed.

The registry record does not report the numerical results for the primary or secondary outcomes, nor does it report how missing outcome data were handled. It does not give the number analyzed for each endpoint, describe withdrawals or losses to follow-up, or state whether participants without a recorded event were censored. These omissions matter because the analysis population and missing-data approach can affect both the estimate and its uncertainty.

The enrollment was 63, while the safety figures use 55 participants at risk. The record does not explain the relationship between those denominators. The difference should not be interpreted as a specific number of withdrawals, exclusions, or missing outcomes because the reasons are not reported in the registry record. Safety denominators also should not be presumed to match the efficacy analysis population.

The record lists zero analyses and does not describe an analysis population such as all enrolled participants or participants who received treatment. Details about intention-to-treat or other analysis conventions, interim looks, and missing-data sensitivity analyses are not reported in the registry record. In the absence of these details, the outcome definitions can be identified, but the analytic handling and robustness of the results cannot be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonitis/pulmonary infiltrates (1.8%).

The safety record reports a Cetuximab group with 55 participants at risk for serious adverse events and 1 affected. For other adverse events, it reports 55 participants at risk and 52 affected. These counts describe the categories in the registry record; they do not identify the specific events experienced by each participant or explain how events were collected and classified.

Pneumonitis/pulmonary infiltrates is listed among the top serious terms at 1.8%. The record does not provide a complete serious-event listing or details on onset, duration, severity grading, outcome, or attribution to treatment. Deaths are recorded as null, so death counts in the safety grouping are not reported in the registry record.

The safety denominator of 55 differs from the enrollment of 63, but the record does not explain why. It is not possible to infer whether this reflects exposure, follow-up, eligibility for safety assessment, or another reason. These figures should be read as the registry's reported safety summaries, not as a complete account of all harms or as a comparison with an untreated group. The single-group design does not provide a randomized safety contrast.

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

The registry record documents a phase II, single-group study of cetuximab in metastatic esophageal or gastroesophageal junction cancer, with overall survival at 6 months designated as the primary outcome. It also documents the treatment schedule, two secondary outcome names, and some adverse-event counts. This information describes the study's focus and selected reported data.

The record does not report the primary survival percentage or its 95% confidence interval. It also does not report the numerical findings for Time to Treatment Failure or Time to Progression. As a result, the posted registry information does not establish the observed magnitude or precision of the efficacy outcomes. The absence of a numerical result in the registry is not itself evidence that an outcome was favorable or unfavorable.

The study had no separate comparator group, according to its single-group model and allocation listed as NA. Therefore, its design does not support a randomized, like-for-like treatment comparison. Even if an outcome estimate were available, a single-group result would describe participants in the study rather than isolate a causal difference from a control condition.

The safety figures provide limited descriptive information. They report serious and other adverse-event counts in the Cetuximab group and identify pneumonitis/pulmonary infiltrates at 1.8% among the top serious terms. They do not provide a complete safety profile, explain the denominator relative to enrollment, or give enough detail to determine event attribution.

These distinctions matter: the record can establish what was studied and what endpoints were named, but the unreported outcome values and analytic details limit conclusions about both effects and uncertainty. The study's completed status does not fill those gaps. Interpretation should remain confined to the design and results actually recorded.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly identified clinical question and limited outcome reporting in the registry record. It specifies a phase II, single-group evaluation of cetuximab, an overall survival endpoint at 6 months, and a 95% confidence interval as the uncertainty measure. Yet the numerical survival estimate and interval are not reported. Naming an endpoint is not equivalent to reporting an estimate that readers can interpret.

The single-group structure is also central to interpretation. It allows outcomes among treated participants to be described, but it does not create a randomized control comparison. This distinction is important because a clinical outcome in one group cannot by itself separate treatment effects from other influences on the outcome. The design should shape the questions asked of any result, rather than be treated as a minor technical detail.

The record's enrollment of 63 and safety denominator of 55 illustrate why denominators need explicit explanation. Without a description of who contributed to each analysis, readers cannot assume that the endpoint and safety populations are the same or determine why they differ. Reporting analysis populations and missing-data handling is part of making estimates interpretable.

Finally, the listed secondary outcomes and adverse-event summaries do not replace the missing primary endpoint result. Statistical interpretation depends on the combination of an estimate, its uncertainty, a clear analysis population, and a design suited to the comparison being considered. The registry supports a careful account of study structure and selected safety data, while also showing how missing results constrain evaluation.

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 main limitation for statistical interpretation is that the primary outcome result is not reported in the registry record. Although overall survival at 6 months is identified and a 95% confidence interval is specified, neither the estimate nor the interval is available. The listed secondary outcomes likewise lack numerical results. Thus, outcome magnitude and precision cannot be assessed.

The study is recorded as single group, with allocation NA and no masking. There is no separate comparator group in this record, limiting the ability to make a direct treatment contrast. The registry does not report eligibility criteria, participant characteristics, or other details needed to assess how well the enrolled group represents the broader population described by the study question.

Enrollment was 63, while the safety summary uses 55 participants at risk. The registry does not explain the denominator difference or report the efficacy analysis population. It also does not describe missing-data handling, censoring, follow-up completeness, or sensitivity analyses. These omissions prevent assessment of whether the observed analyses, if reported elsewhere, would be robust to incomplete outcome information.

The record lists Time to Treatment Failure and Time to Progression but does not define their event criteria or report results. It does not describe the statistical analysis plan, multiplicity handling, interim analyses, or the trial's sample-size justification. The planning assumptions described separately are not a substitute for the study's own design justification. These limitations are specific to the information recorded and should not be treated as evidence that procedures were or were not used outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: S0415 Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer — NCT00096031.
• Registry record last updated 2018-09-26; status last verified 2018-08.
• Results first posted 2012-05-01.
• 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

NCT00096031 is a completed phase II, single-group study sponsored by SWOG Cancer Research Network. It evaluated cetuximab as second-line therapy in metastatic esophageal cancer or gastroesophageal junction cancer. Enrollment was 63; the registry lists a start date of 2004-10 and primary completion in 2008-01.

Cetuximab was scheduled at 250 mg/m^2 on days 1, 8, 15, and 22 of every 28-day cycle. The primary outcome was overall survival at 6 months, with a 95% confidence interval specified. Time to Treatment Failure and Time to Progression were listed as secondary outcomes. Numerical efficacy results and detailed statistical methods are not reported in the registry record.

Safety reporting includes 1 of 55 participants affected by a serious adverse event and 52 of 55 affected by other adverse events. Pneumonitis/pulmonary infiltrates is listed at 1.8% among the top serious terms. The registry does not explain the safety denominator or report deaths in this grouping.