A Study of Capecitabine [Xeloda] in Combination With Trastuzumab [Herceptin] and Oxaliplatine in Patients With Resectable Gastric Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Capecitabine [Xeloda] in Combination With Trastuzumab [Herceptin] and Oxaliplatine in Patients With Resectable Gastric Cancer (NCT01130337), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Disease-free Survival (DFS) at Month 18.

2. Clinical Question

3. Trial Design

This was a completed phase 2, open-label, multicenter study with a non-randomized, single-group design. The registry reports enrollment of 36. Recruitment began in 2010-07, and primary completion was recorded in 2014-06. Because there was no randomized control group, the study design supports description of outcomes in the treated group but does not provide a randomized estimate of how the regimen compares with another treatment or with no treatment.

The planned treatment sequence was perioperative. The registry summary describes capecitabine and trastuzumab for three cycles before surgery to resect the tumor, with oxaliplatin administered as part of the XELOX combination. Capecitabine was described as oral treatment at 1000 mg/m2 on day 1-14 of every cycle. Trastuzumab was described as intravenous treatment with an 8 mg/kg loading dose followed by 6 mg/kg on days 1-14 of every cycle. Oxaliplatin was described as intravenous treatment at 130 mg/m2 on day 1 in every cycle.

For participants achieving complete resection R0 or microscopic residual tumor R1, the summary describes three further cycles of XELOX and trastuzumab, followed by trastuzumab alone to complete 12 months of treatment. The registry does not give a separate arm description beyond identifying the single intervention group. The allocation, masking and model fields indicate that the regimen was not compared across randomized arms and that treatment was open-label.

The posted record lists pathological complete response, complete tumor resection R0 and objective response as secondary outcomes in addition to the primary disease-free survival endpoint. It identifies four outcome measures overall, but reports no outcome analyses. The protocol's sample-size justification, detailed statistical analysis plan and planned handling of any interim analyses are not reported in the registry 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.

Before assignment: Screening period comprised of 35 days. A total of 136 participants were included in the study, of which 36 participants were enrolled and 100 participants discontinued due to screening failures. Abbreviation of AE= adverse event.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population.

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: Intent-to-treat (ITT) population included all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Disease-free Survival (DFS) at Month 18, measured over Month 18.

The primary endpoint is the percentage of participants with disease-free survival at Month 18. It is intended to describe the share of the study population who have not experienced the defined event by that time. The registry defines disease-free survival for participants with complete resection R0 as the time from surgery until documented progression or death from any cause, whichever occurs first. Progression is defined using change in the sum of the longest diameter of target lesions relative to the smallest recorded value since treatment started, with both a greater-than-20-percent increase and a minimum 5 mm increase over the nadir specified. The registry notes that small measurement changes can produce a percentage increase when the sum is very small.

For participants without progression or death, the record describes censoring at the last date on which absence of progression was known, identified as the last response assessment. In general, a disease-free survival endpoint captures time until recurrence or another specified event, rather than response at a single scan alone. Reporting the endpoint at a fixed time can give readers a time-specific summary, while the underlying event-time definition distinguishes participants with observed events from those whose follow-up ends without a documented event.

The endpoint is listed for the ITT population, while its description refers specifically to participants with complete resection R0. How the endpoint was operationalized for other participants in the ITT population is not reported in the registry record. Neither the Month 18 estimate nor its 95% confidence interval is reported, so the endpoint's observed level and precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A percentage endpoint is a binary summary: each participant is classified according to whether the endpoint condition is met, and the percentage describes the share classified as meeting it. For this study, the condition is disease-free survival at Month 18 under the registry's definition. That label does not mean that the registry has reported the result. The primary percentage and its 95% confidence interval are not reported in the registry record.

What does the confidence interval convey?

In general, a confidence interval is an interval estimate that expresses statistical uncertainty around an estimated quantity. It is not a guarantee that the true value lies in a particular interval, and its interpretation depends on the method and assumptions used to construct it. For a percentage, the interval is useful alongside the point estimate because it indicates how precisely the data estimate the underlying proportion. The registry lists a 95% confidence interval as the dispersion measure for the endpoint, but does not report the interval or the calculation method. It is therefore not possible to assess the reported precision or verify the method from the registry record.

How does the endpoint's time component matter?

The title of the endpoint refers to disease-free survival at Month 18, while the description defines an event time measured from surgery for participants with complete resection R0. It also describes censoring participants who have neither documented progression nor death by their last known assessment without progression. In general, censoring indicates that the event was not observed during the available follow-up; it does not establish that the event would never occur. The way censored follow-up is incorporated into a time-specific estimate can affect both the estimate and its precision.

The record does not identify the statistical estimator used for the Month 18 endpoint, the assumptions used to handle censoring, or the detailed rules for the analysis. A common approach for time-to-event data is not evidence that a particular approach was used in this trial. The registry's definition also specifies a measurement rule for progression: the sum of the longest diameter of target lesions must increase by greater than 20 percent relative to the nadir, with a minimum increase of 5 mm over that nadir. The record notes that measurement error can matter when the sum is very small. This detail clarifies the event definition, but does not establish how scans were assessed or whether assessment was independent or blinded; those details are not reported in the registry record.

Why is the study design relevant?

In general, random assignment can help make treatment groups comparable at the start of a trial, supporting a causal comparison between groups. This study is recorded as non-randomized and single-group, with no masking. It therefore has no internal randomized comparison. The single-group design can describe the outcomes recorded among participants receiving the regimen, but it cannot separate treatment effects from other influences by comparing the study group with a randomized control group. Open-label status also means the registry does not describe masking of treatment assignment, though it does not report how outcome assessments were conducted.

The study is identified as phase 2 and reports enrollment of 36. These design details do not reveal how enrollment was chosen or whether the study was planned to estimate the primary percentage with a specified precision. The sample-size justification is not reported in the registry record. A sample-size planning illustration based on an observed effect is a separate planning exercise, not the trial's original design justification or an observed-power result. In particular, an illustration assuming equal allocation between two arms and a normal approximation does not describe this single-group trial's allocation. No trial-specific sample-size calculation or target precision is reported in the registry record.

What can secondary outcomes add?

The registry lists pathological complete response, complete tumor resection R0 and objective response as secondary outcomes. These outcomes describe different aspects of response and surgery from disease-free survival. In general, examining multiple outcomes can offer a broader description of a study, but it also raises questions about which results were prespecified and how the chance of false-positive findings was managed. The record does not provide the secondary outcome results, their analysis methods, or any adjustment strategy. Four outcome measures are identified, but no analyses are listed.

Statistical interpretation depends on both the observed data and the analysis plan. Here, the registry describes the primary endpoint and identifies an intended confidence interval, but does not give the endpoint estimate, interval, analysis procedure, or population count used for analysis. The event definition and censoring description support understanding what was intended to be measured; they are not enough to reconstruct the analysis or its result. Any estimate or conclusion beyond the registry's posted information would require assumptions not documented in the registry record.

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+Trastuzumab")
n      <- c(36)
events <- c(27)
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+Trastuzumab  36  27  75.0  57.8  87.9  58.9  86.2  58.8  86.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists disease-free survival at Month 18 as the primary outcome and identifies pathological complete response, complete tumor resection R0 and objective response as secondary outcomes. It reports four outcome measures overall, but lists no analyses. The registry record does not report a multiplicity strategy, such as an adjustment for testing several outcomes, nor does it explain whether any outcomes were treated as exploratory. Without analysis results and a stated testing plan, readers cannot determine how the study handled the possibility of chance findings across multiple outcomes.

The primary endpoint population is identified as ITT. In general, an intention-to-treat population aims to retain participants according to their assigned treatment group, but the registry does not describe the operational rules used for this single-group study, the number analyzed, or how participants with missing endpoint data were handled. It also does not report reasons for missing data, completeness of follow-up, or sensitivity analyses. The endpoint description says participants without documented progression or death were censored at their last response assessment, but it does not specify other missing-data procedures or how that rule was implemented in analysis.

The primary endpoint description refers to surgery for complete resection R0 participants, whereas the listed population is ITT. How participants who did not meet that surgical condition were handled for the primary analysis is not reported in the registry record. The protocol, statistical analysis plan, and interim-analysis plan are also not reported in the registry record. These omissions limit assessment of prespecification, analysis choices, and the completeness of the posted results; they do not establish that any particular method was or was not used outside the information recorded in the registry.

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: diarrhoea (13.9%), localised intra-abdominal fluid collection (5.6%), pneumonia (5.6%), pneumothorax (5.6%), cardiogenic shock (2.8%).

The registry records 36 participants at risk for both serious and other adverse events. It records 22 participants affected by serious adverse events and 35 affected by other adverse events. These are participant counts in separate registry categories. They should not be added together because the record does not say that the groups are mutually exclusive; a participant could potentially appear in both categories. The adverse-event entry does not provide enough detail to determine the timing, duration, severity breakdown beyond the serious classification, or relationship of each event to treatment.

The listed serious-event terms and registry percentages are diarrhoea, 13.9%; localised intra-abdominal fluid collection, 5.6%; pneumonia, 5.6%; pneumothorax, 5.6%; cardiogenic shock, 2.8%; and dysphagia, 2.8%. These entries describe terms reported in the registry and are not, by themselves, evidence that the study regimen caused the events. The record does not report a deaths value; deaths are therefore not reported in the registry record, rather than confirmed absent. Adverse-event summaries are descriptive and should be read alongside the limited safety details and the single-group design.

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

The registry record establishes that a completed phase 2 study evaluated a perioperative combination of capecitabine, oxaliplatin and trastuzumab in participants with resectable gastric cancer. It describes an intended treatment sequence around surgery, identifies disease-free survival at Month 18 as the primary endpoint, and gives an event definition that includes progression or death from any cause for participants with complete resection R0. It also lists secondary response and resection outcomes and provides selected adverse-event summaries.

The record does not report the primary disease-free survival percentage or its 95% confidence interval. It also does not report the secondary outcome results or analyses. Consequently, the posted results do not show the observed level or precision of the primary outcome, and they do not support a claim about the efficacy of the regimen. The completed status and enrollment of 36 do not fill this reporting gap. Nor can the safety counts establish that the regimen caused the reported events.

Because the study is non-randomized and single-group, it cannot provide an internal randomized comparison with another treatment. Even if an outcome estimate were posted, the design would make a causal comparison difficult without a suitable comparator and assumptions beyond the information in the registry. A descriptive result for the enrolled group would not, by itself, show what would have happened to comparable participants receiving a different approach.

The endpoint definition, including its censoring rule and progression threshold, helps specify what the study intended to measure. However, the registry does not report the estimator, analysis details, missing-data procedures, or the handling of participants outside the endpoint description's R0 condition. These gaps make it difficult to assess the analysis and its limitations fully. The appropriate reading is therefore narrow: the record documents the design and intended measures, but does not report the primary result needed to characterize disease-free survival at Month 18.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why endpoint definitions and design features need to be read together. Disease-free survival is a time-to-event outcome, and the registry describes both the event—progression or death—and the censoring point for participants without a documented event. It also gives a specific progression threshold based on change from the nadir. These details matter because the event definition, follow-up information and handling of censored observations shape the interpretation of any time-specific estimate.

The design imposes an important boundary on what the results could establish. The registry records a non-randomized, single-group study with no masking. A single group can provide descriptive information, but it does not give the protection against confounding that comes from randomized allocation to a comparator. This distinction is especially important when readers want to move from an observed outcome to a claim about what the treatment caused.

The record also illustrates the difference between a named outcome and a reported result. The primary endpoint and a 95% confidence interval are specified, yet the estimate and interval are not posted. Without those values, there is no basis for assessing the magnitude or precision of the primary result. The listed safety counts contribute descriptive context but do not replace efficacy results or establish treatment causality.

Finally, the registry identifies an ITT population while defining the endpoint in terms of complete resection R0 participants. The absence of reported details about the analysis population, missing observations and multiplicity leaves important questions open. These are not merely technical details: they affect how confidently a reader can interpret estimates and whether results can be compared fairly across outcomes or studies. The record's limitations are therefore central to its statistical interpretation, not peripheral qualifications.

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 most consequential limitation of the posted record is that it does not report the primary Month 18 disease-free survival estimate or its 95% confidence interval. The secondary outcomes are listed without results, and no analyses are listed. This prevents evaluation of the main outcome's magnitude, precision, or consistency with the other intended measures.

The single-group, non-randomized design has no internal control group. It can describe outcomes among participants receiving the regimen but cannot provide a randomized comparison. The registry identifies the primary population as ITT while the endpoint description refers to participants with complete resection R0; the handling of participants who do not fit that description is not reported. The number with evaluable endpoint data, follow-up completeness, missing-data methods, and sensitivity analyses are also not reported in the registry record.

The record does not report the statistical analysis plan, estimator for the time-specific endpoint, sample-size justification, multiplicity strategy, or interim-analysis plan. It describes the progression threshold and censoring at the last response assessment, but does not provide enough information to assess implementation or departures from the intended procedures. The deaths field is null, so mortality cannot be characterized from that field. Safety reporting gives counts and selected serious-event terms, but does not establish treatment causality or provide a full account of event timing and management.

The registry describes an anticipated 12 months on study drug, but the actual duration of treatment and follow-up is not reported in the registry record. These limitations restrict interpretation to the design and descriptive information that is posted; they do not justify filling in unreported outcomes or analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Capecitabine [Xeloda] in Combination With Trastuzumab [Herceptin] and Oxaliplatine in Patients With Resectable Gastric Cancer — NCT01130337.
• Registry record last updated 2015-10-01; status last verified 2015-09.
• Results first posted 2015-10-01.
• 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

The registry record describes a completed phase 2, open-label, non-randomized, single-group study of perioperative capecitabine, oxaliplatin and trastuzumab for resectable gastric or gastro-esophageal junction adenocarcinoma. Enrollment was 36. The primary endpoint was the percentage of participants with disease-free survival at Month 18, with a 95% confidence interval specified. The record defines progression and describes censoring, and lists pathological complete response, complete tumor resection R0 and objective response as secondary outcomes.

The primary endpoint estimate, its confidence interval, secondary outcome results and analyses are not reported in the registry record. Serious adverse events were recorded for 22 of 36 participants, and other adverse events for 35 of 36. The record lists selected serious-event terms and percentages, but does not report a deaths value. Because there was no randomized comparator, the study does not provide an internal comparative treatment estimate.