Study of IMC-11F8 in Participants With Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of IMC-11F8 in Participants With Colorectal Cancer (NCT00835185), a na phase 2 study. The primary outcome is Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response ).

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, multicenter study of IMC-11F8 in combination with mFOLFOX-6 in participants with treatment-naïve, locally advanced or metastatic colorectal cancer. The registry record lists a single group and no masking. Allocation is listed as NA, and the study is completed. Enrollment is listed as 44. The study start is recorded as 2007-08 and primary completion as 2010-01.

The single group received IMC-11F8 (necitumumab) once every 2 weeks together with oxaliplatin, 5-FU and FA. Because the study did not include a separate comparator group, its design does not provide a concurrent control for separating the regimen’s observed outcomes from other influences. The open-label design also means that masking was not used, as recorded by the registry.

The primary outcome was the percentage of participants with CR or PR, assessed using RECIST version 1.0. The stated assessment period was up to 30 months. Secondary outcomes included overall survival, progression-free survival, duration of response, adverse events, serious adverse events or death, immunogenicity, and pharmacokinetic measures of IMC-11F8. The registry lists 18 outcome measures, but the primary response estimate and its uncertainty are not reported in the registry record.

The number enrolled is not necessarily the number included in the primary endpoint population: that population was defined as enrolled participants who received any quantity of study drug. The count meeting this definition is not reported in the registry record. A detailed statistical analysis plan, the rationale for the planned enrollment, and 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: Participants with known best overall response and off study treatment were considered to be completed.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received any quantity of study drug.

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 enrolled participants who received any quantity of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response ), measured over Up to 30 Months.

The primary endpoint was the percentage of participants with an objective response, defined as a complete response (CR) or partial response (PR). Under the stated RECIST version 1.0 definitions, CR required disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of target lesions, relative to the baseline sum.

This endpoint turns tumor-response classifications into a proportion of the treated study population. As a general statistical point, a proportion can describe how often a defined event occurred in a specified group. Its meaning depends on both the event definition and the population used in the denominator. Here, the registry specifies participants who received any quantity of study drug as the population and describes counting responses from treatment start until disease progression or recurrence.

The registry gives the timeframe as up to 30 months and identifies a 95% confidence interval as the measure of dispersion. In general, a confidence interval expresses the uncertainty around an estimated quantity under the method used; it is not a guarantee that the true value lies within a particular interval. The observed response percentage and interval are not reported in the registry record, nor is the number of treated participants in the endpoint population. Consequently, the endpoint’s definition is available, but its estimate and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary classification at the participant level: a participant either met the CR-or-PR definition or did not. The registry then defines the endpoint as a percentage of the specified study population. In general, binary outcomes are often summarized by a proportion, which is the count meeting the definition relative to the population evaluated. No new estimate can be derived without the response count and the applicable denominator, and those primary response results are not reported in the registry record.

What does the response definition mean?

RECIST version 1.0 supplies the stated rules for classifying response. CR was defined as disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions relative to the baseline sum. Combining CR and PR into an objective-response endpoint treats either classification as meeting the response criterion. The registry describes counting participants with either response from treatment start until disease progression or recurrence. It does not report separate counts for the two response categories, assessment procedures beyond the stated criteria, or additional details about response review.

Why is the denominator important?

The primary endpoint population is stated to include all enrolled participants who received any quantity of study drug. Enrollment is listed as 44, but the number who received study drug and met the endpoint-population definition is not reported in the registry record. These figures should not be treated as interchangeable. As a general principle, an estimate’s denominator must match its stated analysis population; changes in who is included can affect the interpretation of a proportion. The record does not explain whether any enrolled participants did not receive study drug or how such cases were handled.

What does a confidence interval add?

The stated dispersion measure for the primary endpoint is a 95% confidence interval. In general, the point estimate describes the observed proportion, while the interval describes statistical uncertainty around that estimate under a particular method and its assumptions. The interval does not show the range of individual participant outcomes, and it does not account automatically for every source of bias or uncertainty. Neither the estimate nor its interval is reported in the registry record, and the method used to construct the interval is not reported there.

What can a single-group design estimate?

This study is recorded as a single-group study, with allocation listed as NA and masking listed as none. It can describe outcomes observed in participants receiving the combination regimen. In general, a concurrent comparator helps distinguish differences associated with the study intervention from changes that may occur for other reasons. Without such a group, within-trial comparative treatment effects cannot be estimated. The study design also cannot isolate the effects of IMC-11F8 from the effects of the mFOLFOX-6 components.

The open-label design means participants and study personnel were not masked, according to the registry entry. As a general matter, lack of masking can matter when outcomes involve judgment or when knowledge of treatment may influence reporting or assessment. The endpoint uses specified imaging response criteria, but the record does not report further details about assessor masking or independent review. No assumptions about those procedures should be made.

How should the safety counts be understood?

The registry lists a group with 44 participants at risk for serious adverse events and 16 affected, and 44 at risk for other adverse events and 44 affected. It also lists selected serious adverse-event terms with percentages. These are safety summaries, not estimates of a randomized comparison. A participant may experience more than one event or event term; the registry does not state that the listed terms are mutually exclusive. The death count is not reported in the registry record. In general, event counts, affected-participant counts, and event rates are different summaries and should not be conflated.

What analysis details are unavailable?

The registry lists no analyses. The statistical analysis plan, confidence-interval calculation method, missing-data procedures, handling of participants with no post-baseline assessment, and interim-analysis plan are not reported in the registry record. The rationale for the planned enrollment is also not reported. Although a planning illustration may use assumptions about significance level, allocation and effect size, those assumptions are not evidence that the trial achieved a particular power. Sample-size illustrations are planning tools, not observed power, and the registry does not report the trial’s own sample-size justification.

Multiplicity concerns arise when several outcomes or comparisons are considered. As a general statistical point, testing multiple hypotheses can increase the chance of at least one apparently notable result if no adjustment or prespecified hierarchy is used. The record lists multiple secondary outcomes, but any multiplicity strategy or hierarchy is not reported in the registry record. No claim about adjustment, confirmatory status, or selective reporting can be made from the listed information alone.

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("IMC-11F8 (Necitumumab) + mFOLFOX-6")
n      <- c(44)
events <- c(28)
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  IMC-11F8 (Necitumumab) + mFOLFOX-6  44  28  63.6  47.8  77.6  48.9  76.2  48.8  76.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary objective-response outcome and secondary outcomes including overall survival, progression-free survival, adverse events, duration of response, immunogenicity and pharmacokinetic measures. It lists 18 outcome measures. The registry record does not report a multiplicity procedure or a hierarchy specifying how multiple outcomes were to be interpreted. As a general statistical point, considering several outcomes can create multiple opportunities for chance findings; prespecified testing strategies can help manage that issue. Whether such a strategy was used in this study is not reported in the registry record.

The registry lists no analyses, and the primary objective-response estimate is not reported in the registry record. The record does not state how missing response assessments, participants without evaluable follow-up, or other incomplete data were handled. It also does not report whether any analysis population differed from the primary endpoint population defined as enrolled participants who received any quantity of study drug. The number of participants meeting that definition is not reported.

In general, missing-data methods matter because participants with unavailable outcome measurements may differ from those with observed outcomes. Different assumptions about missing outcomes can lead to different estimates. Without the study’s procedures and outcome data, the impact of missingness cannot be evaluated. A statistical analysis plan, interim-analysis details and a sample-size justification are also not reported in the registry record. These omissions limit assessment of how outcome analyses were planned and whether reported results, if available elsewhere, follow prespecified methods.

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: intestinal obstruction (6.8%), diarrhoea (4.5%), febrile neutropenia (2.3%), abdominal pain (2.3%), gastrointestinal obstruction (2.3%).

The registry lists 16 participants affected by serious adverse events among 44 at risk, and 44 participants affected by other adverse events among 44 at risk. The record also lists selected serious adverse-event terms: intestinal obstruction, 6.8%; diarrhoea, 4.5%; febrile neutropenia, 2.3%; abdominal pain, 2.3%; gastrointestinal obstruction, 2.3%; and large intestine perforation, 2.3%. These figures are descriptive entries for the study group, not a comparison against an untreated or alternative-treatment group.

In general, an affected-participant count summarizes participants with at least one event within the relevant category, whereas event-term summaries describe particular reported terms. The registry does not state that the terms are mutually exclusive, so they should not be added or treated as separate, non-overlapping groups. The percentages are quoted as recorded; the record does not provide further detail about their calculation or event-term coding.

The death count is not reported in the registry record. The safety summaries do not establish that an event was caused by the regimen, and the single-group design does not provide a concurrent safety comparator. They should be read as descriptions of reported events in this study, not as standalone evidence of comparative risk.

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

The registry record establishes that a completed, open-label, single-group Phase II study evaluated IMC-11F8 with mFOLFOX-6 in participants with treatment-naïve, locally advanced or metastatic colorectal cancer. It also defines the primary endpoint: the percentage of participants with CR or PR under RECIST version 1.0, assessed over a timeframe of up to 30 months. These registry entries describe the research question and design, not the size of the response observed.

The primary response percentage and its 95% confidence interval are not reported in the registry record. The number of participants who received any quantity of study drug, which defines the primary endpoint population, is also not reported. Therefore, the record does not permit an assessment of the observed response frequency or its precision. Results for the listed secondary outcomes are likewise not reported in the registry record.

As a general distinction, describing an outcome in a treated group is not the same as establishing that treatment caused the outcome. This study has no separate comparator group, so it cannot provide a within-trial randomized comparison. Nor can it separate the contribution of IMC-11F8 from the chemotherapy regimen given with it. The open-label design and the information unavailable about assessment and analysis procedures further constrain interpretation.

The safety entries describe adverse events recorded for the study group. They do not, on their own, establish causation or comparative risk. The registry does not report the death count. Overall, the available record supports a description of the design, endpoint definitions and listed safety counts, but not a conclusion about the magnitude or precision of efficacy outcomes or how those outcomes compare with another treatment.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how design determines the questions an outcome estimate can answer. The primary endpoint was a proportion: the percentage of participants meeting the combined CR-or-PR definition. Such an estimate is interpretable only alongside its endpoint population, event definition and uncertainty. The registry specifies those definitions, but does not report the response estimate, the confidence interval or the number in the treated endpoint population.

The single-group design also defines the limits of inference. It can describe what was observed among participants given the combination regimen, but it does not supply a concurrent control for estimating a comparative treatment effect. Because IMC-11F8 was combined with mFOLFOX-6, the design also cannot disentangle the contributions of the regimen’s components. These are design limitations, not findings about whether the regimen did or did not produce responses.

The record’s safety summaries offer another statistical distinction: affected-participant counts and selected event-term percentages describe different aspects of adverse events, and the event terms should not be assumed to be mutually exclusive. The listed summaries provide no randomized comparison, and causation cannot be established from these counts alone.

Finally, a completed study record and a stated outcome definition do not substitute for outcome results or analysis details. The primary result, secondary outcome results, missing-data procedures, multiplicity approach, sample-size justification and interim-analysis details are not reported in the registry record. Recognizing what is documented—and what remains unavailable—is necessary for a calibrated reading of clinical trial evidence.

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 primary limitation for interpreting efficacy is that the registry record does not report the objective-response percentage or its 95% confidence interval. It also does not report the number of participants who received any quantity of study drug and therefore met the stated primary endpoint population definition. Enrollment is listed as 44, but the endpoint denominator cannot be assumed from enrollment alone.

The study had a single group, no masking and no separate comparator. Its results, if available, would describe outcomes in the treated group rather than provide a randomized comparison. Because the investigational agent was given in combination with mFOLFOX-6, the design cannot isolate the contribution of any one component. The open-label design may also be relevant to assessment and reporting, but further details about assessment procedures are not reported in the registry record.

The registry lists secondary outcomes, but their results are not reported. It does not report how missing outcome data were handled, whether response assessments were independently reviewed, the method used for the confidence interval, a multiplicity strategy, or a detailed statistical analysis plan. The sample-size justification and interim-analysis details are also not reported. These absences limit assessment of precision, analysis choices and the handling of multiple outcomes.

Safety interpretation is constrained by the descriptive single-group summaries. The registry does not report the death count or state that the listed serious adverse-event terms are mutually exclusive. Counts in this record should not be read as comparative risks or as evidence that an event was caused by a particular component.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of IMC-11F8 in Participants With Colorectal Cancer — NCT00835185.
• Registry record last updated 2016-01-29; status last verified 2015-12.
• Results first posted 2016-01-29.
• 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 a completed, open-label, multicenter Phase II study of IMC-11F8 (necitumumab) with mFOLFOX-6 in participants with treatment-naïve, locally advanced or metastatic colorectal cancer. It lists a single group, no masking, allocation as NA, and enrollment of 44. The primary endpoint was the percentage with CR or PR under RECIST version 1.0, with a stated timeframe of up to 30 months.

The registry record does not report the primary response percentage, its 95% confidence interval, or the count in the treated endpoint population. It lists secondary outcomes and descriptive adverse-event summaries, but secondary outcome results and the death count are not reported. A detailed statistical analysis plan, missing-data methods, multiplicity approach and sample-size justification are not reported in the registry record.