Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma (NCT01208103), a na phase 2 study. The primary outcome is Number of Participants With Progression-free Survival (PFS) at Six Months.

2. Clinical Question

The clinical question is therefore about the outcome observed in a group receiving the three-drug regimen, not whether the regimen outperformed another treatment. Without a concurrent comparator, the study cannot separate outcomes associated with the regimen from other influences on participants’ disease course. The record lists response rate, overall progression-free survival, overall survival, and adverse events as secondary outcomes. Their results are not reported.

The study concerns a rare cancer setting and a combination regimen. Its primary endpoint focuses on remaining alive without documented progression through a specified follow-up point. This is a time-to-event outcome: participants’ follow-up contributes information up to progression, death, or the end of available observation, depending on the recorded event and censoring. The registry description does not state how those details were handled in the analysis.

3. Trial Design

This is a phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists enrollment of 30, a start date of 2011-05-06, primary completion on 2018-03-07, and status COMPLETED. The record does not describe a randomized allocation; allocation is listed as NA. Masking is listed as NONE.

Participants received oxaliplatin and bevacizumab intravenously on day 1, with capecitabine by mouth twice daily on days 1–14. The courses were scheduled to repeat every 21 days in the absence of disease progression or unacceptable toxicity. The registry does not give additional treatment details beyond this schedule in the record.

The primary outcome is the number of participants with progression-free survival at six months, expressed as a percentage of participants. The registry describes progression-free survival as the interval from first treatment during which a participant lives without progression. The planned estimate is based on the Kaplan-Meier method, with a 95% confidence interval listed as the dispersion measure. The actual endpoint estimate and interval are not reported in the registry record.

The listed secondary outcomes concern response rate, overall progression-free survival, overall survival, and adverse events. There are five outcome measures in total. Although the primary outcome description mentions a Bayesian sequential monitoring design, the record does not give further monitoring details. The statistical analysis plan, sample-size justification, and analysis populations are not reported in the registry record.

Because there is no control arm, the design describes outcomes within the treated group rather than a treatment contrast. The enrollment figure does not by itself explain how the study’s size was chosen or how much precision was expected for the endpoint.

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 Progression-free Survival (PFS) at Six Months, measured over 6 months.

The primary endpoint is the number of participants with progression-free survival at six months, reported as a percentage of participants. Progression-free survival concerns the time from first treatment until disease progression or death; the registry’s description emphasizes living without progression during and after treatment. The endpoint asks whether participants remain alive and progression-free through the specified six-month assessment point.

This endpoint is used because it captures both the timing of disease progression and survival without progression, rather than counting tumor response alone. In general, time-to-event methods can use information from participants whose event has not been observed by the end of their follow-up, while accounting for the time they were observed. The registry names the Kaplan-Meier method for estimating progression-free survival. It does not describe the censoring rules or event-adjudication procedures.

The record lists a 95% confidence interval as the measure of uncertainty. In general, a confidence interval shows the range of values reasonably compatible with the data under the method’s assumptions; it communicates precision, not proof that a treatment caused an outcome. Neither the six-month estimate nor its confidence interval is reported in the registry record. The endpoint’s definition and planned method can therefore be described, but its observed magnitude and precision cannot be evaluated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a planned Bayesian sequential monitoring design and Kaplan-Meier estimation for the primary progression-free survival endpoint. It does not report the detailed analysis plan or the primary numerical result. The explanations below are general descriptions of the named methods, not claims about unreported implementation choices.

What does a single-group design estimate?

A single-group design observes outcomes among participants receiving the study regimen. It can summarize the course of outcomes in that group, but it does not directly estimate what would have happened to the same participants under another treatment. Randomized comparative designs use concurrent groups to support a treatment contrast; this record lists no control group and no randomized allocation. As a result, an observed outcome within this study would not, by itself, identify the causal effect of the regimen.

What does Kaplan-Meier estimation do?

In general, the Kaplan-Meier method estimates the probability of remaining event-free over time from observed event times and censored follow-up. A participant whose event has not been observed by the end of available follow-up can still contribute information up to that point. The method relies on assumptions about censoring and the observation process. The registry names Kaplan-Meier estimation, but does not report how progression or death was defined for analysis, how censoring was handled, or how events were confirmed.

The primary endpoint is expressed as a percentage of participants with progression-free survival at six months. For an endpoint at a specified time, the Kaplan-Meier estimate summarizes the estimated probability of remaining progression-free through that time. The registry does not include the resulting percentage. It is therefore not possible to explain the size of the estimate or evaluate its uncertainty from this record.

How should the confidence interval be read?

In general, a confidence interval describes uncertainty around an estimated quantity under a specified statistical procedure and its assumptions. A point estimate alone can hide substantial uncertainty, especially when the amount of observed event information is limited. The registry lists a 95% confidence interval for the primary outcome, but does not give the interval or state how it was calculated. The confidence level does not mean that an individual participant has a 95% chance of a particular outcome.

What does sequential monitoring mean?

In general, sequential monitoring allows accumulating study data to be reviewed over time according to prespecified rules. A Bayesian approach represents uncertainty using probability distributions and may update those distributions as information accumulates. The registry says that a Bayesian sequential monitoring design will be used, but gives no monitoring boundaries, review schedule, prior distributions, decision criteria, or report of interim reviews. Those details cannot be inferred from the design label.

Why does over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than is present, uncertainty may be understated and intervals or tests may be misleading. This concept is relevant to choosing and checking models for count or binary outcomes, but the registry does not identify an over-dispersion issue or describe a model for the reported outcome. There is no basis to claim that it affected this study.

What can sample-size illustrations show?

In general, a sample-size calculation is conditional on assumptions about the effect to detect, the statistical test, allocation, and desired power. The planning illustrations are distinct from the trial’s own design justification, which is not reported in the registry record. Such illustrations are not observed power and do not reveal whether the study was adequately sized for its actual endpoint. In this record, the primary endpoint estimate needed to evaluate an effect-based illustration is also not reported.

The registry lists no analysis results in its analysis field. That does not establish that no analyses were conducted; it means that analysis details are not recorded there. Without the result, interval, model specifications, and analysis population, the named methods can be explained but their implementation and consequences cannot be independently assessed.

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("Bevacizumab + Capecitabine + Oxaliplatin")
n      <- c(30)
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  Bevacizumab + Capecitabine + Oxaliplatin  30  20  66.7  47.2  82.7  48.8  80.8  48.6  80.8

11. Multiplicity, Missing Data and Analysis Populations

The record lists a primary endpoint and secondary outcomes concerning response rate, overall progression-free survival, overall survival, and adverse events. Considering several outcomes can raise the possibility of multiplicity: the more analyses used to support claims, the greater the chance that an apparently notable result could arise by chance. In general, a prespecified testing hierarchy or adjustment can help manage this issue. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized beyond naming a primary endpoint, or which analyses were intended to support formal claims.

The record gives no primary result and no numerical results for the listed secondary outcomes. It also does not describe missing-data methods, censoring rules, or the analysis populations used for efficacy or safety. For a time-to-event endpoint, incomplete follow-up is commonly represented through censoring, but the specific approach and assumptions are not reported. The number of participants included in each analysis, and whether anyone was excluded from an analysis, are also not reported in the registry record.

The primary endpoint description names Bayesian sequential monitoring, but the record does not state how repeated looks at accumulating data were managed or what thresholds guided decisions. Those details matter because monitoring rules can affect interpretation of estimates and statistical evidence. Their absence in the record means the design label should not be treated as a complete account of the monitoring plan.

Any sample-size values shown in planning material are illustrations, not evidence of observed power or of the original justification for enrollment. The trial’s sample-size rationale is not reported in the registry record. These gaps limit assessment of outcome selection, missingness, analysis populations, and the handling of repeated testing.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3.3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: upper gastrointestinal hemorrhage (3.3%), dehydration (3.3%), non-cardiac chest pain (3.3%), abdominal pain (3.3%).

The registry safety fields list 30 participants at risk for serious adverse events and 4 affected. For other adverse events, it lists 30 at risk and 30 affected. These are counts in the posted record; they should not be read as comparisons with another treatment because the study is single-group.

The listed serious-event terms are upper gastrointestinal hemorrhage, dehydration, non-cardiac chest pain, and abdominal pain, each shown as 3.3%. The record does not clarify whether these term-level percentages count participants with each event, event occurrences, or another reporting unit. A participant may experience more than one event, so term counts should not automatically be added or interpreted as distinct people.

The adverse-event field also lists deaths as 30. The registry record does not explain in this summary whether this is all deaths during a specified follow-up period, deaths attributed to an adverse event, or another definition. The figure should not be taken as evidence that treatment caused deaths. Timing, attribution, event duration, and comparative safety data are not reported. These safety entries are useful descriptions of what the registry records, but they do not establish causation or permit a controlled safety comparison.

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

The study asks whether a three-drug regimen can be evaluated in a group with advanced small intestinal or ampulla of Vater adenocarcinoma, using progression-free survival at six months as its primary outcome. The registry records the study design, treatment schedule, endpoint definition, and selected safety information. It does not report the primary endpoint estimate or its 95% confidence interval. Without those values, the central outcome cannot be quantified from this record.

Even a complete outcome estimate from this single-group study would describe participants in the study rather than establish how outcomes compare with another treatment. There is no concurrent control group and no randomized allocation recorded. The design therefore does not remove differences in prognosis, participant selection, follow-up, or other influences that could affect outcomes.

The serious and other adverse-event counts are also descriptive. They indicate what the registry safety fields record among participants at risk, but do not show whether the regimen caused an event or whether its frequency differs from an alternative. The ambiguity around the deaths field and the lack of additional event details further constrain interpretation.

In general, a result should be read together with its uncertainty, endpoint definition, analysis population, and design. Here, the registry names a Kaplan-Meier method and a 95% confidence interval but gives no observed primary result, interval, or detailed analysis plan. The page can explain the statistical framework and the limits of the available record, but it cannot establish that the regimen is effective or ineffective, or quantify its comparative safety.

The absence of a result in this record is not itself a result showing no progression-free survival or no effect. It means the registry entry does not report the value needed to assess the primary question. Conclusions beyond the design and listed safety fields would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable as a phase II, single-group investigation of a combination regimen in advanced adenocarcinoma of the small bowel or ampulla of Vater. The design illustrates a distinction central to clinical research: an endpoint can be clearly defined, and a method can be named, without the registry record containing the numerical result needed to interpret the study’s primary question.

The six-month progression-free survival endpoint is a time-to-event measure summarized with Kaplan-Meier estimation. This makes follow-up and censoring important parts of interpretation. A percentage at a specified time is not simply interchangeable with a count of observed events, because the method uses the timing and availability of follow-up. The record does not provide the event, censoring, or interval details needed to assess that estimation in practice.

The single-group design also demonstrates why a treatment outcome and a treatment effect are different quantities. An outcome observed in a treated group does not by itself show what would have happened under an alternative. Without a concurrent comparison, the registry record cannot establish a causal contrast.

Finally, the entry names sequential Bayesian monitoring but does not give its operational details. Statistical design labels are informative, yet a complete appraisal also needs monitoring rules, analysis populations, missing-data procedures, and reported estimates. These are not reported in the registry record. The study therefore offers a useful case for reading endpoint definitions and design structure carefully while resisting conclusions that the posted record cannot support.

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 central limitation for interpreting this record is that the primary outcome value and its 95% confidence interval are not reported in the registry record. Although the endpoint and intended Kaplan-Meier method are described, the result’s magnitude and precision cannot be assessed.

The study is single-group, with allocation listed as NA and masking listed as NONE. There is no control arm for a direct comparison, and the record does not describe randomization. Consequently, outcomes within the study cannot be interpreted as a causal difference versus another treatment. The registry also does not report participant-level characteristics or enough detail to evaluate how representative the enrolled group was of the broader population described.

Important analysis details are not reported: progression and censoring definitions, event adjudication, follow-up completeness, analysis populations, missing-data handling, and the statistical procedures used to calculate the interval. The record mentions Bayesian sequential monitoring but does not specify its rules or report whether interim reviews occurred. The sample-size justification is not reported.

The safety fields lack contextual detail on timing, attribution, event duration, and the definition behind the deaths entry. The term-level percentages do not establish whether entries represent unique participants or event occurrences. With no comparator, the safety counts cannot support a relative-risk assessment. These limitations are specific to interpreting this trial from the registry record and do not resolve questions that would require a fuller protocol or results report.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bevacizumab, Capecitabine, and Oxaliplatin in Treating Advanced Small Intestinal or Ampulla of Vater Adenocarcinoma — NCT01208103.
• Registry record last updated 2020-09-03; status last verified 2020-09.
• Results first posted 2020-01-18.
• 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 evaluated bevacizumab with capecitabine and oxaliplatin in participants with advanced small intestinal or ampulla of Vater adenocarcinoma. The registry lists enrollment of 30, a start date of 2011-05-06, and primary completion on 2018-03-07. It describes a single-group design with no masking and no randomized allocation.

The primary outcome was progression-free survival at six months, with Kaplan-Meier estimation and a 95% confidence interval specified. The outcome value and interval are not reported in the registry record. The record names response rate, overall progression-free survival, overall survival, and adverse events as secondary outcomes, without reporting their results.

Safety fields list 4 participants with serious adverse events among 30 at risk, and 30 with other adverse events among 30 at risk. The registry also lists deaths as 30, without enough context to interpret attribution or timing. The single-group design and missing outcome results limit conclusions about efficacy and comparative safety.