This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype (NCT01450319), a na phase 2 study. The primary outcome is Overall Survival (OS) Time.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01450319 |
| Phase | Phase 2 |
| Condition | Colorectal Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 73 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
People with refractory colorectal cancer whose tumors had K-RAS mutations and a favorable FcγRIIa polymorphism. The study summary says failure of first- and second-line conventional treatment was documented. The primary endpoint population is described as the MITT analysis set: subjects who received study drug treatment.
Intervention
Cetuximab monotherapy. The registry describes the study as open-label and without a control arm.
Comparator
There was no comparator arm. The study therefore does not provide a randomized or concurrent comparison between cetuximab and another treatment or control condition.
Primary question
What was overall survival, measured from informed consent until death, among treated subjects in this selected population? The endpoint was to be assessed up to 3 years. The numerical median and its confidence interval are not reported in the registry record.
In statistical terms, this is a descriptive question about survival in a defined study group, not an estimate of a treatment contrast. Without a comparator, the study cannot separate outcomes associated with cetuximab from outcomes that might have occurred under another treatment or without study treatment. The genotype and refractory-disease criteria define the population to which the study question applies; they do not by themselves establish that findings would apply to other colorectal cancer populations. The registry lists disease control, progression-free survival, safety, receptor polymorphisms, overall survival by selected biological features, and beta 2-microglobulin among secondary outcomes. Numerical results for those outcomes are not reported in the registry record.
3. Trial Design
The registry describes a phase 2, national, multicenter, open-label study of cetuximab monotherapy. It is classified as a single-group study, and allocation is listed as not applicable. There was no control arm. This design can describe outcomes among enrolled and treated subjects, but it does not create a direct comparison with an alternative treatment. Because treatment was open-label, treatment assignment was not masked; the record does not report any blinded assessment procedures.
Enrollment is recorded as 73. That is the registry enrollment figure and should not be assumed to equal the number in every analysis population. The primary endpoint description defines the MITT analysis set as all subjects who received study drug treatment. The registry does not report the number included in that set or a participant flow accounting for exclusions, withdrawals, or endpoint availability.
The study start is recorded as 2011-12 and primary completion as 2014-12; the record status is completed. The primary outcome was overall survival, defined from the date of informed consent signature until death and assessed up to 3 years. Its stated summary measure is the median with a 95% confidence interval. Numerical estimates for that endpoint are not reported in the registry record.
The registry lists eight secondary outcome measures, covering disease control, progression-free survival, adverse events, receptor polymorphisms, survival related to selected biological features, and beta 2-microglobulin. It records no analyses. Details such as an analysis protocol, sample-size justification, interim monitoring, and handling of deviations from the intended treatment are not reported in the registry record. The absence of a control group is central to interpretation: observed survival can be described, but a causal treatment effect cannot be established by this design alone.
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: A total of 73 subjects were enrolled in the trial. Out of 73 subjects, 70 subjects received the study drug and start the study and three subjects were excluded from the modified intent-to-treat (MITT) analysis set.
Overall Study
| Stage | Cetuximab |
|---|---|
| STARTED | 70 |
| COMPLETED | 70 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: MITT analysis set included all the subjects who received study drug treatment.
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: MITT analysis set included all the subjects who received study drug treatment.
| Characteristic | Unit | Cetuximab |
|---|---|---|
| Participants analysed | 70 | |
| Age, Continuous | Years | 63.61 (SD 10.54) |
| Sex: Female, Male: Female | Participants | 34 |
| Sex: Female, Male: Male | Participants | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival (OS) Time, measured over From the date of informed consent signature until death, assessed up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
Overall survival measures the time from a defined starting point until death. In this study, the starting point was the date of informed consent signature, and the registry says assessment was to continue up to 3 years. The primary endpoint description specifies the MITT analysis set, comprising subjects who received study drug treatment. The planned summary is the median survival time with a 95% confidence interval.
Time-to-event outcomes are useful when the event may occur at different times across participants and follow-up may end before every participant experiences the event. A survival analysis can use the timing of observed events while accounting for follow-up that ends without a recorded event, under the analysis method's assumptions. The median is the point in the estimated survival distribution at which half the population is estimated to have experienced the event. A confidence interval conveys uncertainty around that estimate; it does not guarantee that the true value lies within the interval.
The registry record does not report the median overall survival or its confidence interval. It also does not report a numerical hazard ratio for the primary endpoint. Consequently, the endpoint's definition and planned summary can be described, but the posted registry information does not allow assessment of the estimated survival duration or its precision. The endpoint alone would not establish a treatment effect in this single-group study, because no concurrent comparator is described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies overall survival as the primary endpoint and states that it was measured from informed consent until death, with assessment up to 3 years. The planned summary is a median and 95% confidence interval in the treated-subject MITT analysis set. However, the registry record does not report the numerical median, confidence interval, event count, or numerical hazard ratio. The primary endpoint result therefore cannot be characterized for magnitude or precision from this record.
This distinction matters. An endpoint definition says what was intended to be measured; it is not itself an outcome estimate. A median would describe the estimated survival distribution in the study population, while its confidence interval would indicate statistical uncertainty. Without the estimate and interval, it is not possible to assess whether the survival estimate is precise or highly uncertain. The record also does not provide enough information to reconstruct a survival curve or determine how follow-up and censoring affected the estimate.
The design further limits interpretation. This was a single-group, open-label study without a control arm. Any survival observed among participants is a description of this selected group, not a direct contrast with another treatment. The record cannot show what outcomes would have been in a comparable group under a different treatment or no study treatment. Differences between this group and another population could also reflect differences in eligibility, disease history, or other characteristics rather than treatment.
The registry records enrollment of 73, but does not report the number included in the primary analysis or how many deaths occurred. The adverse-event data list 70 at risk in the serious-event field and 17 affected, and list 70 at risk and 69 affected in the other-event field. Those entries describe safety reporting and should not be used to infer the primary survival result. The death count in the safety record is not reported.
There are eight listed secondary outcome measures, but no analyses are recorded, and numerical results for those outcomes are not reported in the registry record. No conclusions about disease control, progression-free survival, or subgroup survival can be drawn from outcome titles alone. Overall, the registry provides the study question and design but not the numerical primary result required to evaluate its estimated value and precision.
9. Statistical Methods Explained
The statistical methods that can be described from the registry are limited to the stated endpoint summary and the design information. Overall survival is a time-to-event outcome. The endpoint starts at informed consent and ends at death; the planned assessment period is up to 3 years. The registry specifies a median and 95% confidence interval. It does not report a numerical estimate, a confidence interval, or a detailed analysis procedure.
What does a median survival estimate describe?
For a time-to-event outcome, the median is the time at which the estimated survival function reaches the point corresponding to half of the population having experienced the event. It is a summary of the distribution of event times rather than an average. It does not say that every participant experienced the event at that time, and it does not describe how event risk changes throughout follow-up. A median can be difficult to estimate when follow-up is limited or when too few events have occurred; the registry does not report whether that affected this study.
How should a confidence interval be read?
A confidence interval expresses sampling uncertainty around an estimate under the statistical procedure used. A narrower interval indicates greater precision under that procedure, while a wider interval indicates less precision. The interval is not a guarantee that the true value is contained within its particular bounds. The registry names a 95% confidence interval for the median but does not report the interval limits or the method used to calculate it. Without those details, readers cannot judge the reported estimate's precision or examine the interval calculation.
What does a hazard ratio contribute?
A hazard ratio compares event rates over time between groups in an analysis that includes a comparison. The registry's methods description says that only sponsor-reported hazard ratios are used for time-to-event outcomes. No numerical sponsor-reported hazard ratio is reported in this record, and the study is single-group with no control arm. A within-study treatment-versus-control hazard ratio therefore cannot be read from the available information. A hazard ratio, when reported, is not the same quantity as a median survival time and does not directly state how many months separate group medians.
Why does the single-group design matter statistically?
A single-group study estimates outcomes among the participants who received the study drug. A randomized comparison instead estimates a contrast between groups assigned to different conditions, helping balance measured and unmeasured prognostic factors on average. In a study without a control group, the observed outcome has no concurrent counterfactual for comparison. Historical comparisons would require additional data and assumptions, neither of which is reported in the registry record. Open-label status also means the study was not masked, although the registry does not specify whether any endpoint assessment was performed independently.
How should the planning assumptions be understood?
The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, its stated approach uses a total event count under the Schoenfeld method; other outcomes use participants per arm. These are planning assumptions, not evidence that the trial itself was designed using those assumptions. The record does not provide the illustrated sample-size values or an actual two-arm comparison for this single-group study. Planning sample sizes are not observed power, and they cannot replace the study's outcome estimates.
What is not documented?
The registry records no analyses. It does not report a detailed statistical analysis plan, a sample-size justification for the trial, interim analyses, the censoring rules, the estimator used for the median, or procedures for missing outcome data. Those details should not be inferred from the endpoint label or from general practice. The registry's stated primary endpoint population includes subjects who received study drug treatment, but the number in that analysis population is not reported. As a result, neither the exact analysis denominator nor the completeness of follow-up can be assessed from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight secondary outcome measures in addition to the primary overall-survival outcome. These include disease control rate, progression-free survival, safety outcomes, receptor polymorphisms, overall survival related to selected biological features, and beta 2-microglobulin. The record does not report analyses or numerical results for these secondary outcomes.
When a study examines several outcomes or subgroup questions, multiplicity can arise because the chance of at least one apparently unusual result can increase as more questions are tested. Common approaches include defining a hierarchy of outcomes or adjusting interpretation for multiple testing. The registry record does not report whether any multiplicity strategy was planned or used. It is therefore not possible to determine how secondary or subgroup findings, if any, were handled statistically. The outcome list alone does not establish that all listed measures were analyzed or that they were confirmatory.
Missing-data procedures are also not reported in the registry record. The endpoint description identifies the MITT analysis set as subjects who received study drug treatment, but the number in that set, the number with complete follow-up, and the handling of unavailable endpoint information are not stated. For survival outcomes, follow-up may end before death is observed; methods for treating such observations and assumptions about censoring are important, but the registry does not describe them.
The record also does not report an analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of whether analyses followed a prespecified plan, how much uncertainty was anticipated, and how incomplete data may affect estimates. No assumptions about those procedures can be made from the registry entry.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Cetuximab | 17 | 70 | 24.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cetuximab | 69 of 70 |
Most frequent serious adverse event terms
| Event term | Organ system | Cetuximab |
|---|---|---|
| Cholestaticjaundice | Hepatobiliary disorders | 1 of 70 |
| Acute cholecystitis | Hepatobiliary disorders | 1 of 70 |
| Cholangitis | Hepatobiliary disorders | 1 of 70 |
| Liver failure | Hepatobiliary disorders | 1 of 70 |
| Pyrexia | General disorders | 1 of 70 |
| Pain | General disorders | 1 of 70 |
| General malaise | General disorders | 1 of 70 |
| Catheter point infection | Infections and infestations | 1 of 70 |
| Listeria meningitis | Infections and infestations | 1 of 70 |
| Urinary tract infection | Infections and infestations | 1 of 70 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cetuximab |
|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | 39 of 70 |
| Asthenia | General disorders | 32 of 70 |
| Decreased appetite | Metabolism and nutrition disorders | 16 of 70 |
| Constipation | Gastrointestinal disorders | 15 of 70 |
| Nausea | Gastrointestinal disorders | 12 of 70 |
| Vomiting | Gastrointestinal disorders | 11 of 70 |
| Mucosal inflammation | General disorders | 10 of 70 |
| Pyrexia | General disorders | 10 of 70 |
| Back pain | Musculoskeletal and connective tissue disorders | 10 of 70 |
| Abdominal pain | Gastrointestinal disorders | 9 of 70 |
Serious events with the highest arm-level rate: cholestaticjaundice (1.4%), acute cholecystitis (1.4%), cholangitis (1.4%), liver failure (1.4%), pyrexia (1.4%).
The safety record lists 70 at risk and 17 affected in its serious-event fields. It separately lists 70 at risk and 69 affected in its other-event fields. These are registry entries, not a comparative estimate of risk: the study had one cetuximab group and no control arm. The death count is not reported in the safety record.
The listed serious-event terms are Cholestaticjaundice, Acute cholecystitis, Cholangitis, Liver failure, Pyrexia, and Pain. Each term is shown with a value of 1.4%. The registry information does not explain the denominator or calculation behind each percentage, so those values should be read as recorded rather than used to infer a different denominator. The terms and percentages do not establish how events were related to treatment or how their severity was adjudicated.
Counts and percentages in safety reporting describe events as recorded under the study's reporting framework; they do not, by themselves, establish causality. The registry record does not provide event-level timing, exposure duration, or a comparison group. It also does not report the number of adverse events leading to discontinuation or death in the primary safety summary. These limitations mean the entries can be described, but should not be interpreted as a complete comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The study asks a focused question about overall survival in refractory colorectal cancer with specified K-RAS mutation and favorable FcγRIIa genotype features, among subjects receiving cetuximab monotherapy. Its design is phase 2, open-label, and single-group, with enrollment recorded as 73. The primary endpoint is defined clearly enough to identify the time origin, event, assessment period, summary measure, and analysis population.
What the registry does not provide is the numerical primary outcome. The median overall survival and its 95% confidence interval are not reported in the registry record. The record also does not report the number of deaths or a numerical hazard ratio. Thus, it is not possible from this information to state the observed survival estimate, quantify its precision, or assess whether estimates vary over follow-up.
Even if a numerical survival estimate were available, a single-group study would describe outcomes in its treated population rather than establish a causal contrast against another treatment. Without a concurrent control arm, differences from outcomes in another setting could reflect patient selection, disease history, follow-up, or other factors. The registry does not provide a basis for resolving those possibilities.
The listed secondary outcomes and safety entries add context about what the study intended to track, but numerical secondary outcome results are not reported. The safety listing includes serious-event counts and terms, but no comparator, and the death count is not reported. These observations should not be stretched into claims about benefit, lack of benefit, or comparative safety. The record supports a description of the study question and design; it does not support a treatment-effect conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable for the distinction between a clearly named endpoint and an unavailable endpoint result. Overall survival is a familiar time-to-event measure, and the registry specifies its origin, event, follow-up limit, summary statistic, and analysis population. Yet without the median and confidence interval, readers cannot evaluate the estimated survival or its precision. This illustrates why endpoint definitions and outcome estimates answer different questions.
The single-group design also clarifies the difference between describing an outcome and estimating a treatment effect. A study can characterize survival among participants receiving an intervention, but a treatment contrast requires a comparator and a defensible basis for comparing groups. The registry explicitly describes no control arm, so the design does not provide a concurrent comparison. That limitation is structural, not something that can be repaired by interpreting a survival estimate as if it were comparative.
The entry also lists several secondary outcomes and biological subgroup questions. Such breadth makes prespecification and multiplicity handling relevant to interpretation, but those methods are not reported in the registry record. The listing alone does not tell readers which analyses were conducted, whether they were exploratory, or how uncertainty across multiple questions was considered. The record states no analyses.
Finally, the study's stated planning illustration is not the same as the trial's own design rationale, and planning sample sizes are not observed power. The registry does not report a trial sample-size justification. Together, these points show how design, analysis transparency, and outcome reporting shape what a clinical study can establish, independently of the clinical topic being studied.
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.
The most direct limitation of the registry information is that it does not report the numerical primary endpoint result. Although overall survival is defined and a median with a 95% confidence interval is specified, neither the estimate nor interval is available in the registry record. Event counts and the number included in the primary analysis are also not reported. This prevents evaluation of the endpoint's magnitude and precision.
The single-group, open-label design has no control arm and cannot provide a randomized treatment comparison. The record does not report blinded endpoint assessment. It also does not give enough participant-flow information to connect the enrollment figure of 73 to the treated analysis population or to establish how complete follow-up was.
Statistical details that would aid interpretation are not reported: the analysis plan, sample-size justification, interim analyses, censoring procedures, handling of missing data, and multiplicity strategy. The record lists secondary outcomes but does not report their numerical results or analyses. The safety record includes event counts and percentages but does not report the death count or clarify the percentage denominators.
These limitations are specific to what the registry record documents. They do not establish that unreported procedures were absent from the study; they mean those procedures cannot be assessed from this record. No additional protocol details or outcome values should be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype — NCT01450319.
- Registry record last updated 2016-11-28; status last verified 2016-10.
- Results first posted 2016-06-15.
- 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.
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18. Record Summary
The registry describes NCT01450319 as a completed phase 2, national, multicenter, open-label, single-group study of cetuximab monotherapy in refractory colorectal cancer with K-RAS mutation and favorable FcγRIIa genotype features. Enrollment is recorded as 73. The study summary says failure of first- and second-line conventional treatment was documented.
Overall survival was the primary endpoint, measured from informed consent until death and assessed up to 3 years. The planned summary was the median with a 95% confidence interval in subjects who received study drug treatment. The numerical primary result is not reported in the registry record. The record lists eight secondary outcomes and no analyses. It describes no control arm, and the safety record's death count is not reported.