A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab (NCT00845039), a randomized phase 2 study. The primary outcome is Progression-Free Survival (PFS) Rate at 18 Weeks.

2. Clinical Question

3. Trial Design

NCT00845039 is recorded as a randomized Phase 2 clinical trial with a parallel-group model and no masking. It compared cetuximab plus irinotecan against cetuximab, irinotecan, and IMC-A12. Because the study was unmasked, treatment assignment was not concealed from participants or study personnel in the way it would be in a blinded trial. The registry does not report further details about the randomization process, allocation concealment, or how treatment assignment was implemented.

The trial enrolled 4 participants and is listed as terminated. The recorded start was 2009-05, and the recorded primary completion was 2011-02. The registry describes the intended setting as metastatic K-Ras wild type colon or rectum cancer that had progressed on oxaliplatin and bevacizumab given as first-line therapy. The study purpose was to assess the value of adding IMC-A12 to irinotecan and cetuximab.

The two treatment groups differed by the inclusion of IMC-A12. Both included cetuximab 500 mg/m² and irinotecan 180 mg/m²; the combination group also included IMC-A12 10 mg/kg. The registry lists several secondary outcomes, including objective response rate, overall survival, progression-free survival over the entire duration, resection rate, toxicity, serum measures, and quality of life. Although these outcomes are listed, the registry record does not report analyses for them in the information.

Randomization is intended to support a fair comparison by distributing participant characteristics across groups on average. In a small trial, however, randomization cannot ensure that groups are similar in practice, and estimates can be highly uncertain. Here, the small enrollment and the decision not to summarize the primary outcome sharply limit what can be learned about comparative outcomes from 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Zero participants analyzed. Per Clinical Study Report, decision made by ImClone and NSABP at time of study closing to not perform summary analysis on N= 4 due to validity of data related to low number of participants and concerns on maintaining participant confidentiality for low number of participants.

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: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Progression-Free Survival (PFS) Rate at 18 Weeks, measured over Approximately 18 Weeks.

The primary endpoint was the progression-free survival (PFS) rate at 18 weeks, with a timeframe described as approximately 18 Weeks. PFS generally concerns the time a participant remains alive without disease progression; a rate at a specified assessment time expresses the share meeting that status at that time. The endpoint combines information about progression and death, but the registry record does not provide the detailed event definition, assessment schedule, censoring rules, or calculation method used for this trial.

A fixed-time PFS rate can be useful because it expresses outcome status at a clinically interpretable point in follow-up. It can support a comparison between treatment groups if outcomes are collected and analyzed in a way that allows the estimate and its uncertainty to be assessed. That requires enough valid follow-up and outcome information to produce a meaningful summary.

For this trial, the registry says that zero participants were analyzed for the primary endpoint. It also reports that the decision was made at study closing not to perform a summary analysis on N= 4, citing data-validity concerns related to the low participant count and confidentiality concerns. Therefore, no PFS rate or comparative estimate is reported. The endpoint name alone does not establish what the result would have been, nor does it permit a conclusion about the relative outcomes of the treatment groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help translate collected outcomes into estimates and quantify uncertainty. The registry record for this trial identifies a randomized, parallel-group design, but it does not report the detailed analysis procedures for the primary outcome. The methods discussion below distinguishes general statistical principles from what is documented for this trial.

What does randomization contribute?

General: Randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences in prognostic characteristics between groups, so that a later outcome comparison is less vulnerable to confounding. Randomization does not guarantee balance in every trial, especially when enrollment is small. It also does not resolve problems with incomplete outcome data, measurement, follow-up, or analysis.

For NCT00845039, the registry identifies the allocation as randomized but does not report the randomization sequence method, concealment procedure, or any stratification factors. The design label therefore describes the broad allocation approach, not every operational detail needed to evaluate its implementation.

What would a PFS rate estimate mean?

General: A PFS rate at a fixed time is an estimate of the proportion of a defined group that has not experienced progression or death by that time, subject to the endpoint definition and analysis rules. When follow-up differs across participants or some outcomes are not observed, methods for time-to-event data can account for censoring, meaning that a participant's exact event time is not known but their follow-up contributes information up to a recorded point.

The registry names PFS rate at 18 weeks as the primary endpoint and gives a timeframe of approximately 18 Weeks. It does not report the event criteria, timing and method of disease assessments, rules for censoring, or estimator used. More importantly, it reports zero participants analyzed and no summary analysis. A rate cannot be reconstructed from the endpoint label or from enrollment information alone.

Why are estimates and uncertainty important?

General: An estimate describes the observed contrast or outcome, while an uncertainty interval indicates how imprecise that estimate may be under the assumptions of the analysis. A small amount of information usually makes estimates less precise, although the degree depends on the outcome and data. Statistical significance, when reported, answers a different question from the size and precision of an effect. A non-significant result does not establish equivalence or absence of an effect.

No primary endpoint estimate, confidence interval, or significance test is reported in the registry record. It is therefore not possible to evaluate effect size, precision, or statistical significance for the primary PFS comparison. The reason recorded for not analyzing the outcome was the validity of data with a low participant count and participant confidentiality concerns, rather than a reported statistical test result.

How should planning illustrations be read?

General: Sample-size calculations describe the amount of information a future study might require under chosen assumptions. They depend on such choices as the significance level, allocation, statistical model, and effect size to detect. They are planning tools, not results from participants in the trial. Power is a design property under assumed conditions; it is not an observed measure of whether a completed trial detected an effect.

The registry's planning assumptions specify a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event planning, the stated method uses the total number of events, while other outcomes use participants per arm. These are planning assumptions, not evidence that the trial used those procedures in its own design or analysis. The registry record does not report the trial's own sample-size justification. Any planning figures should therefore be understood as illustrations under assumptions, not as observed power or proof about the treatment comparison.

What can event counts tell readers?

General: Event counts describe what was recorded in the groups, but a count alone does not convey uncertainty or account for differences in observation time, participant characteristics, or event definitions. Rates and comparative measures require appropriate denominators and methods. When event counts are very small, estimates can be unstable and a single event can have a large influence on a calculated comparison. Over-dispersion, in general, occurs when observed variability exceeds what a model's assumptions expect; it can make standard errors too small if not handled appropriately. The registry does not report a model for the adverse-event counts, and no such model should be assumed.

For this record, serious adverse-event counts and the listed serious-event terms should be read descriptively. The posted primary-outcome information does not support recalculation of an efficacy contrast. No recalculated result is reported for the primary endpoint, and no sponsor analysis for it is available in the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary PFS rate at 18 weeks. They include objective response rate, overall survival, PFS over the entire duration, resection rate, toxicity, post-treatment serum levels, quality of life, and antibody assessment. When a study examines multiple outcomes, time points, or subgroups, the chance of obtaining an apparently notable result by chance can increase if each is tested without accounting for multiplicity. General approaches include prespecifying a primary comparison, adjusting testing procedures, or treating secondary analyses as exploratory. Which approach was used in this trial is not reported in the registry record.

The registry reports zero participants analyzed for the primary endpoint and says the decision was made not to perform a summary analysis on N= 4. It does not report an analysis population for the secondary outcomes in the information, nor does it say which outcomes were analyzed, how missing observations were handled, or whether any multiplicity adjustment was used. Those omissions prevent assessment of whether outcome testing followed a prespecified plan.

Missing-data methods matter because incomplete follow-up can affect estimates, particularly when the reasons for missingness are associated with health status or treatment. General options depend on the outcome and the assumptions that can reasonably be made about why information is missing. The registry record does not report the extent or pattern of missing outcome data, the reasons for missingness, or an imputation or censoring strategy for this trial.

The absence of an analysis is not itself a missing-data method, and it should not be interpreted as a null result. With no reported primary analysis, no documented multiplicity strategy, and no detailed account of analysis populations, readers cannot determine how the intended statistical controls would have been applied to the trial data.

11. 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: anaemia (50.0%), nausea (50.0%), bile duct obstruction (50.0%), hyperbilirubinaemia (50.0%), aspartate aminotransferase increased (50.0%).

The registry reports serious adverse-event information separately for the two treatment groups. In the cetuximab-plus-irinotecan group, 2 participants were at risk and 0 were affected by a serious adverse event. In the group receiving cetuximab, IMC-A12, and irinotecan, 2 were at risk and 1 was affected. The record also reports that 2 participants in each group were affected in the other adverse-event category. These are descriptive counts, not a comparative estimate of treatment-related risk.

The registry lists Anaemia, Nausea, Bile duct obstruction, Hyperbilirubinaemia, Aspartate aminotransferase increased, and Blood creatinine increased among the serious-event terms, each with a listed percentage of 50.0%. The record as summarized does not specify the group attribution or denominator for each listed term, so the percentages should not be used to infer a group-specific rate or to compare regimens.

Deaths are not reported in the adverse-event figures. The record does not provide further detail about event timing, severity grading, relatedness to treatment, duration, or participant-level overlap across events. General caution applies to small counts: they can be strongly affected by individual observations and offer limited precision. The figures describe reported events; they do not by themselves establish causation or a comparative safety conclusion.

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

The trial record establishes that NCT00845039 was a randomized Phase 2 comparison of cetuximab plus irinotecan with the same regimen plus IMC-A12. Its primary endpoint was PFS rate at 18 weeks. The record also gives a specific reason why no primary summary was produced: the Clinical Study Report says ImClone and NSABP decided at study closing not to analyze the data on N= 4 because of concerns about validity with a low participant count and participant confidentiality.

As a result, the posted results do not show whether the groups differed in PFS. They do not provide an estimate of the magnitude or direction of any difference, or its uncertainty. This is not the same as finding no difference. It is also not a demonstration that either regimen is superior. No treatment conclusion can be drawn from an analysis that the registry says was not performed.

The adverse-event counts provide limited descriptive information. They record serious events affecting 0 participants in the cetuximab-plus-irinotecan group and 1 participant in the group that included IMC-A12; the other adverse-event category affected 2 participants in each group. Such counts do not establish that an event was caused by treatment, and the serious-event percentages cannot be assigned to treatment groups from the listed information. The registry does not report deaths in these adverse-event figures.

The registry lists secondary outcomes, but outcome names alone are not results. No secondary-outcome estimates or analyses are reported in the registry record described for this record. Nor does a planning calculation establish what happened in the trial: planning illustrations are hypothetical calculations under assumptions, not observed efficacy or observed power.

The meaning is therefore bounded by what the record reports. It documents the intended randomized comparison, the primary endpoint, the small enrollment, termination status, and selected adverse-event counts. It does not provide an interpretable efficacy estimate or a complete comparative safety assessment. The absence of a reported result should be preserved as uncertainty, not converted into a claim of benefit, harm, equivalence, or no effect.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a study's design question and the evidence ultimately available for answering it. The design asked whether adding IMC-A12 to cetuximab and irinotecan changed outcomes for participants with metastatic colorectal cancer after progression on first-line oxaliplatin and bevacizumab. But the registry reports no primary PFS analysis. A clearly stated endpoint and randomized design do not, by themselves, produce an estimable or interpretable treatment effect.

It also shows why sample size and information content matter in clinical research. Randomization can reduce systematic allocation bias, but it cannot compensate for insufficiently informative data or resolve concerns about data validity and confidentiality. The Clinical Study Report explanation identifies those concerns as the reason no summary analysis was conducted on N= 4. In this setting, withholding an unstable or potentially identifying summary can leave the main clinical question unanswered in the public record.

For biostatistical interpretation, this record is a reminder not to equate missing analysis with a negative finding. A null result would require an analyzed outcome and an estimate with uncertainty; no such primary comparison is reported. Similarly, the descriptive adverse-event counts should not be elevated into a comparative safety conclusion.

The record also demonstrates why the details of an analysis plan matter. Prespecified endpoint definitions, missing-data rules, multiplicity procedures, and analysis populations help readers understand how results were intended to be generated. These details are not reported in the registry record. Their absence does not imply that no plan existed, but it limits independent evaluation of the planned analysis.

14. 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.

Several limitations are specific to this trial record. Enrollment was 4, and the trial is marked terminated. The registry reports zero participants analyzed for the primary endpoint, PFS rate at 18 weeks. The Clinical Study Report explanation says that a summary analysis was not performed because of data-validity concerns associated with the low participant count and confidentiality concerns. Thus the central endpoint has no reported result for interpretation.

The registry record does not report the reason for termination beyond the explanation for not summarizing the primary outcome. It does not provide detailed eligibility criteria, recruitment or follow-up information, baseline characteristics, treatment exposure, or the outcome assessment procedures in the registry record. It also does not report the randomization implementation, allocation concealment, or an analysis plan. The lack of these details limits assessment of conduct and potential sources of bias.

The record lists a range of secondary outcomes but does not report corresponding analyses in the information. It does not state how missing data were handled, define the analysis populations for those outcomes, or describe multiplicity procedures. For adverse events, counts are available, but event attribution, timing, severity grading, treatment relatedness, and overlap among terms are not fully described. The listed serious-event percentages are not assigned to specific treatment groups in the record.

These limitations do not establish that the treatments were ineffective or that the recorded adverse events were caused by a treatment. They define what can and cannot be concluded from the registry information: the design is described, but the primary comparative outcome is not analyzed, and safety information remains descriptive and incomplete.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Irinotecan and Cetuximab With or Without IMC-A12 for Treatment of Participants With Colon or Rectum Cancer Who Got Worse After Their First Treatment With Oxaliplatin and Bevacizumab — NCT00845039.
• Registry record last updated 2018-07-02; status last verified 2018-06.
• Results first posted 2018-06-01.
• 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.

18. Record Summary

NCT00845039 was a randomized, unmasked, parallel Phase 2 trial of cetuximab and irinotecan with or without IMC-A12 for metastatic K-Ras wild type colon or rectum cancer that had progressed after first-line oxaliplatin and bevacizumab. Enrollment was 4. The record gives a start of 2009-05, primary completion of 2011-02, and status of terminated.

The primary endpoint was PFS rate at 18 weeks. The registry reports zero participants analyzed and cites the decision not to perform a summary analysis on N= 4 because of data-validity and confidentiality concerns. It lists serious adverse-event counts and selected event terms, but does not provide a primary efficacy comparison or a complete comparative safety analysis. Detailed statistical procedures, including the trial's own sample-size justification and missing-data plan, are not reported in the registry record.