A Phase II, Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II, Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer (NCT00383149), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Surviving at 6 Months.

2. Clinical Question

3. Trial Design

This was a Phase II, open-label trial with non-randomized allocation and a single-group model. The listed enrollment is 58. The study is marked completed; the recorded start is 2007-01 and the primary completion date is 2009-06. R-Pharm is identified as the sponsor. These details describe the registry record and do not supply a treatment-effect estimate.

All participants in the treatment arm were assigned the combination of ixabepilone and cetuximab. Ixabepilone was given at a starting dose of 32 mg/m^2 as a 3-hour intravenous infusion every 3 weeks. Cetuximab began with a 400 mg/m^2 intravenous dose over 2 hours, followed by a weekly 250 mg/m^2 intravenous dose over 1 hour. The record does not report dose modifications, treatment duration, or adherence.

The study summary frames the survival question against historical data, rather than a concurrent randomized group. The historical source, its eligibility criteria, and how differences between historical and trial participants were handled are not reported in the registry record. Without random allocation and a concurrent comparator, any numerical comparison with historical experience would be vulnerable to differences in patient selection, care, outcome measurement, and follow-up.

The registry lists 13 outcome measures, including tumor response, progression-free and overall survival, response timing and duration, and adverse events. It records zero analyses. That entry does not provide a statistical analysis plan or explain whether analyses were conducted but not entered in the registry. The record also does not state the trial's sample-size justification, interim analysis plan, or methods for handling censoring and missing observations.

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: Of the 58 participants enrolled, 4 were never treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated participants; all participants who received at least one dose of ixabepilone or cetuximab. Participants who did not die prior to 6 months but dropped out of the study were not included in the numerator.

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 Percentage of Participants Surviving at 6 Months, measured over From time of first dose of study drug through 6 months.

The primary endpoint is the percentage of treated participants surviving at 6 months, measured from the first dose of study drug. The registry defines treated participants as those who received at least one dose of ixabepilone or cetuximab. It defines the numerator as treated participants who had not died before 6 months. Participants who did not die before 6 months but dropped out were not included in the numerator.

A fixed-time survival percentage is a way to describe the proportion of a defined population meeting a survival condition at a specified time point. It can make an outcome easier to communicate than a full time-to-event curve, but it compresses follow-up into a single point and does not show when events occurred or how survival changed over time. Interpretation depends on consistent follow-up and clear handling of participants whose status at the time point is unknown.

The registry record does not report the observed percentage or its stated 95% confidence interval. It also does not explain how participants who dropped out were treated in the denominator, or whether the endpoint was estimated using a survival-analysis method. As a result, the endpoint definition is available, but the numerical survival estimate and its precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a 95% confidence interval communicate?

Generally, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to calculate it. A narrower interval indicates greater statistical precision, while a wider interval indicates less precision. The interval does not remove design limitations, measurement problems, or bias; it quantifies sampling uncertainty conditional on the analysis approach. The registry specifies a 95% confidence interval for the primary outcome but does not report its bounds or the method used to calculate it. Consequently, neither precision nor compatibility with particular survival values can be assessed.

Why does the single-group design matter?

Generally, random allocation helps balance known and unknown participant characteristics between treatment groups, supporting a causal comparison. This trial is recorded as non-randomized and single-group, so there is no concurrent control group in the registry record. A historical comparison, as described in the study summary, does not receive the same protection from differences in who was included or how care and outcomes were recorded. Even a precise survival estimate in the treated group would describe that group; by itself, it would not isolate the effect of the treatment combination.

Historical comparisons may be useful when appropriately selected and carefully aligned with the trial population and outcome definition. The quality of such a comparison depends on details such as eligibility, calendar period, follow-up, and outcome ascertainment. Those comparison details are not reported in the registry record. A numerical difference against an unspecified historical benchmark cannot be interpreted or recalculated.

What is the endpoint's denominator?

The primary outcome is defined among treated participants, meaning people who received at least one dose of either study drug. The registry separately states that the numerator consists of treated participants who had not died before 6 months, while participants who had not died but dropped out were excluded from the numerator. This definition makes follow-up status important: a participant who cannot be followed to the assessment time may not have an observed survival status at that point. The record does not explain the denominator's treatment of such participants beyond the stated definition, nor does it report the number treated or the number with complete endpoint follow-up.

In general, missing outcome information can affect both the estimate and its uncertainty, especially if loss to follow-up is related to prognosis. Methods such as censoring in time-to-event analysis rely on assumptions about follow-up; a simple proportion can require a clear rule for unresolved status. The registry does not report the analytic method or assumptions used for this endpoint, so it is not possible to determine how missing status was handled.

How should the listed adverse-event percentages be read?

The registry lists serious adverse-event terms with percentages, including hypotension and pancreatic carcinoma at 11.1%, dehydration at 9.3%, vomiting at 7.4%, and hypersensitivity and nausea at 5.6%. These are term-level percentages in the serious-event listing. The record does not state in this material whether a participant could contribute to more than one term, and these percentages should not be added or treated as mutually exclusive categories. The registry also lists a common treatment-related nonhematologic adverse-event outcome using a threshold of >25%, but does not report its detailed results.

Adverse-event summaries are descriptive unless a suitable comparison and analysis support a comparative inference. Seriousness, severity grade, and causal relationship are distinct concepts: an event can be serious without its severity grade or causal attribution being established by the event name alone. The record lists serious events and separately describes outcomes concerning treatment-related events by grade; it does not give enough detail to resolve all these dimensions for each listed term.

What can be concluded from zero recorded analyses?

The registry records zero analyses. This indicates that analysis entries are not present in the record, but it does not establish why they are absent or whether analyses were performed elsewhere. A statistical analysis plan, including model choices, confidence-interval construction, censoring rules, and treatment of missing observations, is not reported in the registry record. The reported design and endpoint definition can be described, but the analysis cannot be independently evaluated without those methods and numerical results.

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("Ixabepilone + Cetuximab")
n      <- c(54)
events <- c(31)
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  Ixabepilone + Cetuximab  54  31  57.4  43.2  70.8  44.2  69.7  44.1  69.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, spanning survival, tumor response, response timing, and safety. When several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested independently. Statistical approaches to multiplicity can control or contextualize that risk, but the appropriate approach depends on which outcomes were prespecified, their hierarchy, and the intended claims. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which analyses were intended to support confirmatory conclusions.

The record lists zero analyses. It therefore does not report p-values, model estimates, confidence intervals for secondary outcomes, or any adjustments for multiple testing. The primary endpoint's stated 95% confidence interval also has no numerical bounds recorded in the registry record for this trial analysis. Without results and analysis methods, no claim about statistical significance, consistency across outcomes, or robustness can be made.

Missing-data methods are not reported in the registry record. This matters particularly for a fixed-time survival percentage because participants who stop being followed before the time point may have unknown status. The endpoint definition says that participants who did not die before 6 months but dropped out were not included in the numerator, but it does not fully specify how they contributed to the denominator or how unknown status was handled in estimation. The record does not report follow-up completeness, censoring rules, or sensitivity analyses.

The endpoint population is defined as treated participants, while the listed enrollment is 58. The number treated for the primary endpoint is not reported in the registry record, so the enrollment figure should not be substituted for an outcome denominator.

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: hypotension (11.1%), pancreatic carcinoma (11.1%), dehydration (9.3%), vomiting (7.4%), hypersensitivity (5.6%).

The registry reports 54 participants at risk for the serious adverse-event summary and 32 participants affected. For the other adverse-event summary, it reports 54 at risk and 49 affected. These are counts for the combination group, not comparisons between treatment arms. The number of deaths is not reported in the registry record.

The serious-event term listing includes hypotension and pancreatic carcinoma at 11.1%, dehydration at 9.3%, vomiting at 7.4%, and hypersensitivity and nausea at 5.6%. These percentages describe listed terms; they do not establish that the events were caused by treatment. A participant may potentially have more than one event term, and the record does not specify whether categories overlap. The percentages should not be summed.

Seriousness is not the same as severity grade or treatment attribution. The registry also names outcomes concerning adverse events by grade and treatment relationship, but detailed results for those measures are not reported in the registry record. With no concurrent control group, these figures describe recorded events in the treated group and cannot quantify excess risk compared with another regimen.

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

The registry record identifies a study of ixabepilone plus cetuximab in first-line treatment of metastatic pancreatic cancer and defines survival at 6 months as its primary endpoint. It also reports adverse-event counts and selected serious-event terms. These details establish what was studied and how the primary outcome was defined, but they do not reveal the primary outcome's numerical value.

The record does not report the percentage surviving at 6 months or its 95% confidence interval. It does not report a numerical comparison with historical data. Therefore, the registry information cannot show the magnitude or precision of the observed survival outcome, or support a conclusion that the combination did or did not improve survival. The absence of a reported result is not evidence that the result was favorable, unfavorable, or null.

The design also constrains causal interpretation. Because the trial is single-group and non-randomized, there is no concurrent randomized comparison in the registry record. A historical comparison may provide context, but its source and methods are not reported. Differences between populations or care settings could influence a comparison independently of treatment.

The safety counts document events recorded among participants at risk in the combination group. Without a control group and fuller event-level results, they do not establish comparative safety or causal attribution. Nor do the listed term percentages describe all aspects of severity, duration, or outcome. Those details are not reported in the registry record.

The sound statistical reading is narrow: the trial's design, regimen, endpoint definition, enrollment, and selected safety summaries are recorded, while the primary numerical result and analysis details are absent. Any stronger conclusion would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates a key distinction in clinical-trial interpretation: an endpoint definition is not an endpoint result. The registry clearly specifies survival at 6 months as the primary outcome and describes the treated population and numerator rule. Yet without the observed percentage and its 95% confidence interval, readers cannot assess the estimate's magnitude or precision.

It also highlights the role of a comparator in statistical reasoning. The trial is recorded as single-group and non-randomized, while its summary describes an intended comparison with historical data. That approach can raise a useful research question, but interpretation depends on whether the historical population and outcome measurements are sufficiently comparable. The registry record does not report the historical source or comparative analysis, so those assumptions cannot be examined.

The safety information demonstrates why denominators and outcome definitions matter. The record gives participants at risk and affected for adverse-event summaries, along with selected serious-event terms. These data should be read as descriptive observations, not as a comparison or an estimate of treatment-attributable harm. Seriousness, grade, and causation are separate properties and require their own definitions and reporting.

Finally, the registry lists multiple outcomes but records zero analyses. The absence of analysis details prevents evaluation of multiplicity handling, missing-data assumptions, and the statistical methods used. This is important because reliable interpretation requires not just outcomes of interest, but transparent methods and results. The trial is therefore a useful example of how incomplete outcome reporting limits what can be concluded even when the design and endpoint definitions are available.

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 trial-specific limitation in the registry record is that the primary survival percentage and its 95% confidence interval are not reported. The record also does not give a numerical result for the proposed historical comparison. Without those values, the primary outcome cannot be quantified or evaluated for precision.

The single-group, non-randomized design has no concurrent control group. Although the study summary refers to historical data, the record does not report the source, eligibility criteria, dates, outcome definitions, or analysis used for that comparison. It is therefore not possible to judge comparability or account for potential differences between the trial population and historical participants.

The listed enrollment is 58, but the number of treated participants in the primary endpoint population is not reported in the registry record. The endpoint definition also excludes participants who did not die before 6 months but dropped out from the numerator; the record does not fully specify the denominator handling or estimation method for participants with unknown follow-up status. Follow-up completeness and missing-data sensitivity analyses are not reported.

Although 13 outcome measures are listed, the record includes zero analyses. It does not report the statistical analysis plan, multiplicity handling, endpoint-specific analysis populations, or numerical results for the listed tumor-response and time-to-event outcomes. The safety data are descriptive and lack a concurrent comparison; the number of deaths is not reported. These reporting limitations restrict both efficacy interpretation and comparative safety assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II, Trial of Ixabepilone Plus Cetuximab as First Line Therapy for Metastatic Pancreatic Cancer — NCT00383149.
• Registry record last updated 2016-03-10; status last verified 2016-02.
• Results first posted 2010-10-19.
• 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 II, open-label, non-randomized, single-group trial sponsored by R-Pharm. It lists enrollment as 58 and evaluates ixabepilone plus cetuximab as first-line therapy for metastatic pancreatic cancer. The primary endpoint is the percentage of treated participants surviving at 6 months from the first dose.

The registry specifies a 95% confidence interval for the primary endpoint but does not report the endpoint result or interval. It lists 13 outcome measures and records zero analyses. Safety summaries report 54 participants at risk for each of two adverse-event summaries, with 32 affected for serious events and 49 affected for other events. The record does not report a concurrent control comparison or a numerical historical comparison.