Perioperative Panitumumab and Epirubicin, Oxaliplatin and Xeloda (EOX) in Patients With Gastroesophageal Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Perioperative Panitumumab and Epirubicin, Oxaliplatin and Xeloda (EOX) in Patients With Gastroesophageal Adenocarcinoma (NCT00667420), a na phase 1, phase 2 study. The primary outcome is Safety and Tolerability.

2. Clinical Question

The central question was about delivering the combined regimen through the planned pre-operative treatment period, rather than comparing it with another regimen. The registry identifies the study as a pilot and names safety and tolerability as its primary outcome. Completion of the pre-operative cycles is the specific measure used for that outcome.

The registry also lists R0 resection rate, progression-free survival, pathologic complete response rate and overall survival as secondary outcomes. These outcomes address surgical, pathological and longer-term disease measures, but no numerical results for them are reported in the registry record. The record does not report a treatment-effect comparison against a control group.

Because the study has no concurrent comparator, its primary question is descriptive: it concerns the number completing the stated treatment course in this study. It cannot, by itself, distinguish outcomes associated with the regimen from outcomes that might have occurred under another approach.

3. Trial Design

The registry describes a phase 1 and phase 2 pilot study sponsored by Massachusetts General Hospital. It lists the study as terminated, with a start date of 2008-04 and primary completion in 2011-06. The registry record does not report why the study was terminated.

The design is open-label and single-group, with allocation listed as not applicable and masking listed as none. The intervention is panitumumab in combination with epirubicin, oxaliplatin and Xeloda, also called capecitabine. The arm description gives epirubicin 50mg/m2 by IV on day 1 of each 21 day cycle, oxaliplatin 100 mg/m2 by IV on day 1 of each 21 day cycle, capecitabine 400 mg/m2 twice daily by mouth on days 1-21, and panitumumab 9mg/kg by IV on day 1 of each 21 day cycle.

The primary outcome timeframe is after 3 cycles of pre-operative chemotherapy, described as approximately 21 days per cycle. The primary outcome is the number of participants able to complete those cycles. Enrollment is reported as 17. The record does not report how many enrolled participants received each component, started treatment, or completed the primary-outcome assessment.

There is no like-for-like control group, so the design does not support a randomized comparison between regimens. The registry record does not report details such as eligibility criteria beyond the disease and resectability description, a protocol for dose modification, or the reason for termination. Those details should not be inferred from the phase labels or the pilot designation.

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.

Population: 17 patients with adenocarcinoma of the stomach were enrolled on this study of perioperative EOX-P.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability, measured over after 3 cycles of pre-operative chemotherapy (approx 21 days per cycle).

The primary endpoint is titled Safety and Tolerability. It measures the number of participants able to complete 3 cycles of pre-operative chemotherapy, at a timeframe described as approximately 21 days per cycle. The registry does not report the observed completion count or a numerical result for this endpoint.

In general, treatment completion can serve as a practical indicator of whether participants were able to receive a planned course. It is relevant to tolerability because adverse effects or other difficulties may interfere with continuing treatment. Completion is not, however, a complete account of safety: it does not by itself describe the type, severity, timing or duration of adverse events, nor does it establish why a participant did not complete treatment.

For a count of participants with an outcome, interpretation depends on knowing both who was assessed and how the outcome was defined. The registry gives the completion criterion but does not report an outcome count, an analysis population for this endpoint, or details about participants whose completion status may have been unavailable. Without those results, the primary endpoint cannot be quantified from the registry record.

The separate adverse-event listings provide some safety information, but they do not replace the completion endpoint or explain the reasons for treatment completion or discontinuation. A reader should therefore treat the endpoint description as the planned measure, not as evidence of a particular completion rate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record reports a count-based primary outcome: the number of participants able to complete 3 cycles of pre-operative chemotherapy. It does not report the statistical analysis used for that endpoint, an estimate, or a confidence interval. The explanations below describe general statistical ideas; they should not be read as methods confirmed for this study.

What does a participant count describe?

A count states how many participants met a defined outcome. For an outcome such as treatment completion, a count is easiest to interpret when its denominator is clear: the reader needs to know which participants were eligible for assessment and how missing completion status was handled. A count alone does not show the likelihood of completion in a broader population. A proportion can put a count in context, while a confidence interval can express uncertainty around that estimate. The registry gives the planned completion definition but does not report the completion count, an analysis denominator, a proportion or an interval.

The adverse-event entries likewise use participants with an event as the counting unit. In general, a participant count differs from an event count: a participant may experience more than one event or more than one event type. Consequently, counts across categories should not automatically be summed. The registry lists 6 participants affected by serious adverse events and 13 affected by other adverse events, each among 17 at risk; it also lists frequencies for specific serious adverse-event terms. It does not report enough detail to determine from those term frequencies how events were distributed across participants.

Why does the design affect inference?

In general, random allocation can help create groups that are comparable at the start of a study, while a concurrent control group makes it possible to estimate a between-group contrast. This study is described as single-group, open-label, with allocation not applicable and no masking. It therefore has no randomized comparison. Outcomes in the treated group can be described, but they cannot by themselves establish the difference that would have occurred under another treatment or under no study treatment.

Open-label describes a design without masking; it does not, on its own, tell the reader whether outcome assessment was influenced by knowledge of treatment. The registry record does not report whether assessors were independent or whether any outcomes were assessed using blinded procedures. For an outcome based on treatment completion, the definition is more objective than a subjective rating, but completion alone still does not explain why a participant did or did not finish the cycles.

How should uncertainty be understood?

In general, an estimate from a study is subject to sampling uncertainty. A confidence interval gives a range of values compatible with the data under the method used; it is not a guarantee that the true value lies in that range. A wider interval indicates less precision than a narrower interval. The registry record does not report intervals for the primary endpoint or the listed adverse-event outcomes, and it does not identify an inferential method for them.

For count outcomes, statistical models may make assumptions about how observations vary. Over-dispersion is a general concern when count data vary more than a model assumes; if ignored, uncertainty can be understated. That concept is not evidence that over-dispersion occurred in this study. The primary endpoint is described as a count of participants able to complete treatment, and no model or dispersion assessment is reported in the registry record.

What methods might apply to the secondary outcomes?

In general, resection and pathologic response outcomes are often represented as categorical outcomes, while progression-free and overall survival concern time until an event. Time-to-event analysis can account for participants whose event has not been observed by the end of follow-up, provided follow-up and censoring are defined. The registry names these secondary outcomes but does not report their definitions, follow-up summaries, censoring rules, estimates or analysis methods. No particular method should therefore be attributed to this study.

What does the planning note mean?

The registry includes a planning illustration described as based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It specifies that time-to-event illustrations concern total events, while other illustrations concern participants per arm. These are planning assumptions, not a report of the trial's design: the study itself is described as single-group and has no randomized comparison. Such a calculation is not observed power and does not establish that the study was designed or able to answer a particular question. The registry does not report its own sample-size justification or the analysis plan behind the study.

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("Epirubicin, Oxaliplatin, Capecitabine, Panitumumab")
n      <- c(17)
events <- c(14)
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  Epirubicin, Oxaliplatin, Capecitabine, Panitumumab  17  14  82.4  56.6  96.2  59.0  93.8  58.6  93.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Safety and Tolerability as the primary outcome and names R0 resection rate, progression-free survival, pathologic complete response rate and overall survival as secondary outcomes. It reports 5 outcome measures and 0 analyses. Numerical results for the secondary outcomes are not reported in the registry record.

When a study examines multiple outcomes, the chance of at least one apparently unusual finding can increase if each is tested separately without accounting for the number of questions asked. In general, a prespecified hierarchy or multiplicity adjustment can help control how results are interpreted. The registry record does not report whether outcomes were tested, whether a hierarchy was used, or whether any multiplicity adjustment was planned or applied. It is therefore not possible to determine how the listed outcomes were handled statistically.

The record also does not report how missing outcome data were handled, whether all enrolled participants were included in each outcome analysis, or how participants with incomplete follow-up were treated. It does not identify an intention-to-treat, per-protocol or other analysis population. These are important details because the participants included in an analysis and the handling of unavailable results can affect an estimate.

The terminated status does not explain whether missing data, changes to outcome collection or other issues led to termination; the reason is not reported in the registry record. Without outcome-level analysis details, readers should distinguish the listed outcomes from completed analyses and avoid treating the outcome list as evidence that each outcome was measured or reported.

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: neutropenia (11.8%), diarrhea (11.8%), hypocalcemia (11.8%), amylase (5.9%), colitis (5.9%).

The registry reports 6 participants affected by serious adverse events among 17 at risk, and 13 participants affected by other adverse events among 17 at risk. The listed serious adverse-event terms and frequencies are neutropenia, 11.8%; diarrhea, 11.8%; hypocalcemia, 11.8%; Amylase, 5.9%; Colitis, 5.9%; and Dehydration, 5.9%.

These are descriptive safety figures. The term frequencies should not be added together: the record does not establish that the categories are mutually exclusive, and participants may contribute to more than one category. The listed percentages also do not convey when an event occurred, how long it lasted, its severity grade, whether it recurred, or how it was managed. Those details are not reported in the registry record.

The serious and other adverse-event counts are separate registry entries; they should not be combined into a new total. The record does not give a treatment attribution for each event or a comparison group against which to interpret these frequencies. Accordingly, the figures describe events reported for the study group, but do not establish how the regimen compares with another approach or explain the primary treatment-completion outcome.

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

The registry record establishes that a pilot study of perioperative panitumumab with epirubicin, oxaliplatin and capecitabine was conducted as an open-label, single-group phase 1 and phase 2 study. It reports enrollment of 17, a terminated status, a primary outcome focused on completion of pre-operative chemotherapy, and adverse-event counts and terms. It does not report the primary outcome result or numerical results for the secondary outcomes.

In general, descriptive safety counts can help characterize what was reported in a study group. They do not, on their own, show whether events were caused by treatment, how risks compare with other treatment choices, or how complete the event reporting was. The registry's serious and other adverse-event figures should therefore be read as the posted counts, not as a comparative risk estimate.

The single-group design also constrains conclusions. Without a control group, there is no direct estimate of how the completion, surgical, response or survival outcomes would differ under another approach. A study may provide descriptive information about its enrolled group, but that is distinct from evidence of a causal treatment effect.

The registry record does not report the completion count, confidence intervals, secondary outcome results, detailed analysis methods, missing-data handling, or the reason the study was terminated. These omissions prevent a full assessment of outcome magnitude and precision. The record supports understanding the study's design and the safety entries it lists; it does not, on its own, establish comparative benefit, comparative harm or a definitive estimate of tolerability.

14. Why This Trial Matters Statistically

This study illustrates why the design and outcome definition matter as much as the label attached to an endpoint. Safety and tolerability are broad concepts, while the registered primary measure is specific: the number of participants able to complete 3 cycles of pre-operative chemotherapy. That measure can describe treatment completion, but does not capture every aspect of safety or explain reasons for discontinuation.

The study's single-group structure is central to statistical interpretation. A descriptive count can characterize participants in the study, but a comparative treatment effect requires a basis for comparing outcomes across treatment conditions. The registry lists no concurrent control and describes no randomized comparison. The treatment-completion question is therefore distinct from a question about whether this regimen changes outcomes relative to another approach.

The safety entries also show why participants and events must be distinguished. The registry reports participants affected and separately lists adverse-event terms with frequencies. Those entries should not be added or interpreted as independent categories without supporting detail. Event timing, severity and attribution would contribute important context, but are not reported in the registry record.

Finally, the record demonstrates the difference between registering outcomes and reporting results. It names a primary outcome and secondary outcomes, yet reports 0 analyses and no numerical primary or secondary results. Statistical interpretation depends on estimates, uncertainty measures, analysis populations and missing-data methods, not only on outcome titles. When those details are absent, the appropriate conclusion is limited: the study design and some safety counts are described, while the magnitude and precision of the planned outcomes remain unreported.

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 record describes a small pilot study with enrollment of 17 and no concurrent control group. Because it is single-group and open-label, it does not support a randomized comparison or an estimate of comparative treatment effects. The registry does not report a sample-size justification for the trial, and its planning note describes assumptions for an equal-allocation, two-arm illustration that do not match the listed single-group design.

The primary outcome is defined as the number of participants able to complete 3 cycles of pre-operative chemotherapy, but its result is not reported. The registry also does not report numerical findings for the secondary outcomes. As a result, the listed outcome measures cannot be used to assess completion, resection, response or survival from this record.

Safety reporting is limited to affected-participant counts and a list of serious adverse-event terms with frequencies. The record does not report event-level details such as timing, severity grades, duration, management or attribution. The reason for the terminated status is not reported, so its implications for recruitment, follow-up or outcome collection cannot be determined.

Analysis populations, missing-data methods, confidence intervals, statistical models, multiplicity procedures and the statistical analysis plan are not reported in the registry record. The registry also does not provide enough information to assess whether follow-up was complete or whether outcome definitions changed. These limitations restrict both the precision that can be assessed and the range of conclusions that can be drawn from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Perioperative Panitumumab and Epirubicin, Oxaliplatin and Xeloda (EOX) in Patients With Gastroesophageal Adenocarcinoma — NCT00667420.
• Registry record last updated 2014-07-04; status last verified 2014-07.
• Results first posted 2014-07-04.
• 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 NCT00667420 as a phase 1 and phase 2, open-label, single-group pilot study of perioperative panitumumab with epirubicin, oxaliplatin and capecitabine for resectable gastroesophageal adenocarcinoma. Massachusetts General Hospital is listed as sponsor. Enrollment is reported as 17; the study is listed as terminated, with a start date of 2008-04 and primary completion in 2011-06.

The primary outcome is the number of participants able to complete 3 cycles of pre-operative chemotherapy. The registry lists R0 resection rate, progression-free survival, pathologic complete response rate and overall survival as secondary outcomes, but does not report their numerical results or the primary outcome result. It reports 6 participants affected by serious adverse events among 17 at risk and 13 affected by other adverse events among 17 at risk. The record reports 5 outcome measures and 0 analyses; the reason for termination and detailed statistical methods are not reported in the registry record.