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 Study Evaluating Biomarkers in Patients With Colorectal Cancer and Native KRAS Treated With Chemotherapy + Cetuximab (NCT01276379), a na phase 2 study. The primary outcome is Progression Free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01276379 |
| Phase | Phase 2 |
| Condition | Colorectal Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 221 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Grupo Espanol Multidisciplinario del Cancer Digestivo |
| Results posted | Yes |
2. Clinical Question
The study concerned whether clinical characteristics and biomarkers could help distinguish outcomes among patients receiving first-line chemotherapy with cetuximab for advanced or metastatic colorectal cancer with wild-type KRAS. The registry describes a biomarker-based score intended to define outcome groups, but it does not report the score’s construction or the group-specific progression-free survival results. The treatment was not compared with a control group in this study, so the question is about outcomes and possible differences within a treated cohort rather than a randomized treatment effect.
Population
Patients with advanced and/or metastatic colorectal cancer and wild-type KRAS, treated as first-line therapy. The primary outcome population is described as evaluable. The registry does not report further eligibility details or the number included in the evaluable population.
Intervention
FOLFIRI or FOLFOX-6 with cetuximab. The treatment description specifies biweekly cetuximab at 500mg/m2 for 6 months, followed by biweekly cetuximab monotherapy.
Comparator
There was no randomized control arm: the study is registered as single-group, with allocation listed as not applicable. The planned biomarker-score groups are described for outcome comparisons, but they are not separate treatment arms.
Primary question
What is progression-free survival, measured according to RECIST 1.1, and how does it vary across groups defined by a score based on proposed clinical variables and biomarkers? The registry’s rationale also describes an aim to evaluate biomarkers that might help identify patients with more favorable outcomes during cetuximab treatment. The reported record does not establish whether any biomarker identifies such a group.
3. Trial Design
This completed phase 2 study was prospective, multicenter, open-label, and single-arm. It enrolled 221 participants, with colorectal cancer listed as the condition. The study began in 2011-01 and its primary completion date is listed as 2017-03-15. The sponsor is Grupo Espanol Multidisciplinario del Cancer Digestivo.
Participants received first-line chemotherapy with cetuximab. The registry lists FOLFIRI (m) or FOLFOX-6 (m) with cetuximab; the regimen description specifies cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. It does not report how the choice between chemotherapy regimens was made or provide a treatment-allocation procedure. Masking is listed as none.
The design description refers to defining groups using a score built from proposed clinical variables and biomarkers. It also says outcomes are reported by subgroups according to BRAF mutation. These planned or described subgroup comparisons do not change the registered single-arm structure: every participant belonged to the same treatment/study arm, and there was no randomized comparator. The registry does not report the score’s final specification, its cut points, or the numbers of participants in the resulting groups.
The primary outcome is progression-free survival in the evaluable population, with a four-year timeframe and a median as the reported summary measure. Secondary outcomes listed are overall survival, response duration, frequency of adverse events, secondary biomarker analysis, and tumoral response. The record does not report numerical outcome results for these measures. In particular, it does not give a progression-free survival median or its confidence interval, so the stated design and aims should not be mistaken for evidence about the observed outcomes.
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: All patients were allocated in the same treatment arm. Some patient characteristics and results may be reported according to the mutational status of the patients despite all patients received the same treatment schedule
Overall Study
| Stage | FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab |
|---|---|
| STARTED | 221 |
| COMPLETED | 181 |
| NOT COMPLETED | 40 |
Reasons for not completing this period:
| Reason | FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab |
|---|---|
| Screening failure | 40 |
Analysis population for the primary outcome, as defined in the registry: Evaluable population
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: Evaluable patients
| Characteristic | Unit | WT BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab | Mutant BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab | Total |
|---|---|---|---|---|
| Participants analysed | 161 | 20 | 181 | |
| Age, Continuous | Years | 62 (SD 10.5) | 67 (SD 7.4) | 65 (SD 9) |
| Sex: Female, Male: Female | Participants | 46 | 7 | 53 |
| Sex: Female, Male: Male | Participants | 115 | 13 | 128 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 161 | 20 | 181 |
| Region of Enrollment: Spain | participants | 161 | 20 | 181 |
| Stage: Stage I | Participants | 1 | 0 | 1 |
| Stage: Stage II | Participants | 13 | 0 | 13 |
| Stage: Stage III | Participants | 30 | 5 | 35 |
| Stage: Stage IV | Participants | 117 | 15 | 132 |
| Primary location: Ascending colon | Participants | 23 | 9 | 32 |
| Primary location: Transverse colon | Participants | 12 | 2 | 14 |
| Primary location: Descending colon | Participants | 10 | 4 | 14 |
| Primary location: Sigmoid colon | Participants | 73 | 3 | 76 |
| Primary location: Rectum | Participants | 43 | 2 | 45 |
| Surgery of the primary tumor | Participants | 91 | 10 | 101 |
| Performance Status (PS): ECOG 0 | Participants | 112 | 7 | 119 |
| Performance Status (PS): ECOG 1 | Participants | 49 | 13 | 62 |
| Number of metastatic organs: 1 | Participants | 87 | 7 | 94 |
| Number of metastatic organs: 2 | Participants | 58 | 11 | 69 |
| Number of metastatic organs: 3 | Participants | 15 | 2 | 17 |
| Number of metastatic organs: 4 or higher | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival, measured over 4 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival is a time-to-event outcome. In general, it measures the time until disease progression or death, according to the endpoint’s specified event rules. The registry says progression was assessed using RECIST 1.1 criteria and that CT scans were the main assessment technique. It identifies the primary outcome population as evaluable and sets the timeframe as four years. The registry record does not give further detail on assessment schedules, event adjudication, censoring rules, or how deaths and incomplete follow-up were handled.
The primary summary is the median progression-free survival, with a 95% confidence interval. In general, the median is the point in the event-time distribution by which half of the observed event-time experience lies on either side; it is not an average duration. A confidence interval conveys uncertainty around an estimated value under the analysis assumptions. Its width matters alongside the estimate: a wide interval indicates less precision than a narrow interval.
This endpoint is relevant to a study assessing disease progression during treatment, and the time-to-event form can use information from participants whose follow-up differs. However, the record does not report the median, confidence interval, or other primary endpoint results. It therefore supports describing how progression-free survival was defined and intended to be summarized, but not stating its observed value or drawing a conclusion about the treatment’s effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically focused biomarker question but does not report the numerical primary outcome results needed to answer it. The primary endpoint is median progression-free survival with a 95% confidence interval, assessed using RECIST 1.1. Neither the median nor its interval is reported in the record. The record also does not provide a hazard ratio or a numerical comparison between the biomarker-score groups. Consequently, the magnitude and precision of any observed difference in progression-free survival cannot be described from this information.
The study’s design limits what an outcome comparison can mean. Participants received chemotherapy with cetuximab in one registered study arm. The intended groups were defined by a score using clinical variables and biomarkers; those groups are not randomized treatment assignments. If their outcomes differed, that would describe an association within the treated cohort. It would not by itself show that the biomarker caused the difference, or that treatment effects differ according to the biomarker. Without a control arm, the study also cannot isolate the contribution of cetuximab from the chemotherapy regimens or other features of care.
The design description states that outcomes are reported by BRAF mutation subgroups, but it does not provide subgroup sizes, estimates, confidence intervals, or tests. It also gives no details on the final biomarker score or how participants were assigned to its groups. Those omissions prevent assessment of subgroup precision and of whether the proposed classification was evaluated as planned. These details are not reported in the registry record.
Any sample-size calculations accompanying the posted results should be read as planning illustrations based on an observed effect, not as observed power or as trial outcomes. The registry’s design description says the sample-size planning used a log-rank method and anticipated a minimum 20% difference (60 vs. 40%) in progression-free survival at 12 months between groups, with a bilateral alpha error of 5% and beta error of 20%. These are design assumptions, not evidence that the expected difference occurred.
Overall, the record establishes the study’s population, treatment, endpoint, and biomarker-oriented purpose. It does not establish the numerical progression-free survival result, how precisely it was estimated, or whether the biomarkers separated outcomes. The absence of those results should not be replaced with an inference from the study rationale or from the planned design assumptions.
9. Statistical Methods Explained
The registry describes a time-to-event primary outcome and gives some information about the intended design calculations. It does not report a full statistical analysis plan or numerical primary outcome analysis. The distinctions below help separate the stated design choices from general statistical interpretation.
What does a time-to-event endpoint capture?
In general, a time-to-event analysis concerns both whether an event occurs and when it occurs during follow-up. This differs from reducing each participant’s experience to a simple event/no-event count at one fixed time. Participants may have different observed follow-up, and some may not have had an event by the time their observation ended. Statistical methods for time-to-event data can account for this structure through censoring, subject to the method’s assumptions and the accuracy of the recorded event and follow-up information.
For this study, progression-free survival is the primary endpoint, assessed according to RECIST 1.1, with CT scans described as the main technique. The registry does not specify the detailed event definition beyond that description, assessment schedule, censoring rules, or handling of missing assessments. Those analysis details are not reported in the registry record, so the exact operational treatment of follow-up cannot be reconstructed from the endpoint description alone.
What does the median and confidence interval tell the reader?
The registry specifies a median and a 95% confidence interval as the primary summary. In general, the median gives a central point in the distribution of event times and is less sensitive than a mean to unusually long observed times. It does not describe every participant’s experience or provide a complete picture of the event-time distribution. A confidence interval indicates the uncertainty associated with an estimate under the analysis model; it is not a range containing a fixed proportion of individual participants’ event times.
Precision depends on the amount and timing of outcome information, not just the enrollment figure. The number of events, duration and completeness of follow-up, and censoring pattern can all affect the information available for estimating a time-to-event outcome. The registry record does not report the primary median, its interval, or the event and censoring information needed to discuss precision for this study.
Why does the design description mention a log-rank method?
The registry’s primary outcome description says a log-rank method was used to calculate the sample size, in order to include incidents during follow-up. In general, the log-rank approach is used to compare time-to-event experience between groups. In the design context described, it is a planning method for the proposed score-defined groups, not proof that a particular comparison was statistically significant or that the anticipated separation was observed. The registry does not report the full calculation details or a statistical analysis plan that would establish how every endpoint analysis was performed.
The record describes an anticipated minimum 20% difference (60 vs. 40%) in progression-free survival at 12 months between groups. It also states a bilateral alpha error of 5% and beta error of 20%. These values describe assumptions for the planning calculation. They should not be interpreted as observed outcomes, and they do not establish the study’s achieved precision. The registry does not report how those assumptions were justified or whether they were changed.
What can subgroup comparisons establish?
The registry says outcomes are reported by BRAF mutation subgroups and describes groups based on a score built from proposed clinical variables and biomarkers. In general, a comparison between such subgroups can describe whether outcome patterns differ in the observed cohort. When subgroup membership is not randomized, differences can also reflect other characteristics that vary between groups. A subgroup association is not, by itself, proof of a predictive biomarker or evidence that a treatment has a different causal effect across subgroups.
Interpreting subgroup estimates also requires attention to the number of participants and events in each group, the definition of the groups, and the precision of each estimate. The record does not report the score details, subgroup counts, or subgroup-specific estimates and intervals. It therefore does not permit a detailed assessment of those comparisons.
How should planning illustrations be read?
In general, a sample-size calculation asks how much information might be needed to detect a specified effect under selected assumptions. It is conditional on those assumptions and on the analysis method. A planning illustration based on an observed effect is not an estimate of the probability that the original study detected an effect, and it is not observed power. It also does not substitute for confidence intervals or the trial’s own analysis.
The accompanying planning assumptions describe equal allocation between two arms and a normal approximation for the illustration; for time-to-event outcomes, the stated method gives a total number of events. These are features of the planning illustration, not a description of this study’s allocation: the registry classifies it as single-group, with allocation not applicable. No calculated planning values or primary outcome estimates are reported in the registry record. The calculations should therefore be treated as hypothetical planning context, not as additional observed evidence.
10. Multiplicity, Missing Data and Analysis Populations
The study lists a primary progression-free survival outcome and secondary outcomes that include overall survival, response duration, frequency of adverse events, secondary biomarker analysis, and tumoral response. It also describes outcome reporting by BRAF mutation subgroup and a proposed score based on clinical variables and biomarkers. Considering multiple endpoints, biomarkers, or subgroups can increase the chance of finding an apparently notable result by chance, particularly when many comparisons are explored.
The registry record does not report a multiplicity-adjustment strategy, a hierarchy for testing outcomes, or which comparisons were intended to be confirmatory rather than exploratory. It does not describe a prespecified statistical analysis plan in enough detail to determine how the analyses were selected or interpreted. A correction for multiple comparisons should not be assumed, and neither should the absence of one.
The primary outcome is identified as applying to an evaluable population, but the record does not define that population or explain how participants entered or left it. It also does not report missing-data procedures, censoring rules, or sensitivity analyses. Without those details, it is not possible to assess how incomplete measurements or follow-up were handled, or how robust the findings would be under alternative assumptions.
These gaps are especially relevant to biomarker work, where group definitions and comparisons need clear specification. The score’s variables and cut points, the handling of missing biomarker values, and the intended analysis of BRAF subgroups are not reported in the registry record. The registry’s description of planned groups does not provide enough information to distinguish a prespecified classification from a post hoc one.
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 |
|---|---|---|---|
| FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab | 173 | 218 | 79.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab | 136 of 218 |
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 |
|---|---|
| FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab | 198 of 218 |
Most frequent serious adverse event terms
| Event term | Organ system | FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 53 of 218 |
| Skin reaction | Skin and subcutaneous tissue disorders | 29 of 218 |
| Diarrhoea | Gastrointestinal disorders | 28 of 218 |
| Asthenia | General disorders | 19 of 218 |
| Mucositis | Gastrointestinal disorders | 14 of 218 |
| Intestinal obstruction | Gastrointestinal disorders | 10 of 218 |
| Vascular disorders NOS | Vascular disorders | 10 of 218 |
| Infections | Infections and infestations | 9 of 218 |
| Nausea | Gastrointestinal disorders | 9 of 218 |
| Xerosis | Skin and subcutaneous tissue disorders | 8 of 218 |
Most frequent non-serious adverse event terms
| Event term | Organ system | FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab |
|---|---|---|
| Cutaneous reaction | Skin and subcutaneous tissue disorders | 134 of 218 |
| Asthenia | General disorders | 101 of 218 |
| Mucositis | Gastrointestinal disorders | 87 of 218 |
| Diarrhoea | Gastrointestinal disorders | 80 of 218 |
| Neuropathy | Nervous system disorders | 72 of 218 |
| Nausea | Gastrointestinal disorders | 60 of 218 |
| Fistula | Gastrointestinal disorders | 47 of 218 |
| Paresthesia | Nervous system disorders | 45 of 218 |
| Constipation | Gastrointestinal disorders | 40 of 218 |
| gastrointestinal disorders | Gastrointestinal disorders | 40 of 218 |
Serious events with the highest arm-level rate: neutropenia (24.3%), skin reaction (13.3%), diarrhoea (12.8%), asthenia (8.7%), mucositis (6.4%).
The registry lists one treatment group for adverse-event reporting. It gives a serious-event at-risk count of 218 and an affected count of 173; for other adverse events, the at-risk count is 218 and the affected count is 198. It also lists 136 deaths. These are registry counts, not rates calculated. The record does not state the observation period or provide enough detail to interpret the deaths as treatment-related.
The listed serious adverse-event terms include neutropenia at 24.3%, skin reaction at 13.3%, diarrhoea at 12.8%, asthenia at 8.7%, mucositis at 6.4%, and intestinal obstruction at 4.6%. These percentages should be read as reported, without inferring a different denominator or converting them into counts. The registry does not specify the event-grading system, reporting window, or attribution rules in the information.
Because the study has no control arm, these safety figures cannot establish whether an event was more or less common than it would have been under another treatment. They describe events recorded for the treated group; causal attribution and comparative risk are not reported.
12. What the Result Does, and Does Not, Mean
The record documents a prospective, multicenter phase 2 study of chemotherapy with cetuximab in patients with advanced and/or metastatic colorectal cancer with wild-type KRAS. Its stated statistical aim was to evaluate clinical variables and biomarkers in relation to progression-free survival, including groups formed from a proposed score and reporting by BRAF mutation. The primary endpoint and its planned summary are identifiable, as are several secondary outcomes.
What the record does not provide is the numerical primary result. No median progression-free survival, 95% confidence interval, group-specific estimate, hazard ratio, or inferential result is reported in the information described. Consequently, the result cannot be characterized as precise or imprecise, and no magnitude of association between a biomarker and outcome can be stated. Design assumptions about anticipated differences are not observed results.
The single-arm structure is important. Even if outcomes differed between groups defined by biomarkers, those groups were not randomized to different treatments. Such a difference could reflect differences in prognosis or other participant characteristics rather than a treatment-specific biomarker effect. Since there is no control group, the study also cannot estimate the comparative effect of adding cetuximab to chemotherapy from its design alone.
The adverse-event record provides counts and listed serious-event percentages, but it does not give a comparative safety analysis or details sufficient to interpret attribution and timing. These data describe reported events in the treatment group; they do not establish how those events compare with another regimen.
The study’s purpose and design are therefore clearer than its reported outcome evidence in this registry record. A complete interpretation would require the numerical outcome estimates, their uncertainty, subgroup definitions and results, and more detail on the analysis and missing-data procedures. None of those missing details should be inferred from the study’s rationale or planning assumptions.
13. Why This Trial Matters Statistically
This trial is statistically notable for the difference between its biomarker-comparison aim and its registered treatment design. It is single-arm, while the primary outcome description proposes comparing groups defined by clinical variables and biomarkers. That distinction matters: a prognostic association within a treated cohort is not the same as evidence that a biomarker predicts differential benefit from treatment. A treatment-predictive claim generally depends on comparing treatment effects across biomarker groups, which this single-arm design does not do.
The record also illustrates why endpoint definitions and analysis results need to be considered separately. It specifies progression-free survival, RECIST 1.1 assessment, a median and 95% confidence interval, and a time-to-event planning method. Those details explain the intended measurement framework, but they do not supply the observed estimate or its uncertainty. Without the numerical results, readers cannot judge the size or precision of the outcome.
Planning assumptions are another important distinction. The anticipated group difference and error levels describe inputs to a design calculation. They do not show that the anticipated difference occurred, and they should not be confused with the results of the completed study. Sample-size illustrations based on an observed effect remain planning exercises rather than observed power.
Finally, the registry lists biomarker and BRAF subgroup aims without reporting the score specification, subgroup estimates, or multiplicity procedures. Those omissions matter because subgroup findings can be sensitive to definitions and the number of comparisons considered. The record makes the intended questions visible, while leaving key information needed to assess the statistical strength of the answers unreported.
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 central limitation for interpreting efficacy is that numerical primary outcome results are not reported in the registry record. The median progression-free survival and its 95% confidence interval are absent, as are the estimates for the proposed score-defined groups. The registry record therefore does not support a quantitative assessment of the primary outcome or its precision.
The study has no randomized comparator. It includes chemotherapy with cetuximab in a single registered treatment arm, so outcomes cannot isolate the contribution of cetuximab or establish comparative treatment effects. Biomarker-group comparisons, if made, are observational within the treated cohort. The record does not provide the score definition, cut points, or group sizes needed to evaluate those comparisons.
Further details on analysis are not reported in the registry record. These include the full statistical analysis plan, event and censoring rules, assessment schedule, missing-data handling, and multiplicity strategy. The record identifies an evaluable population but does not define it. The registry also does not give numerical results for the listed secondary outcomes or sufficient detail to evaluate the adverse-event reporting period and attribution.
The design rationale gives a planned difference and error assumptions, but their justification and any subsequent changes are not reported. These assumptions cannot replace observed estimates. Together, these limitations mean that the record describes the intended questions and methods more fully than it reports the evidence needed to answer them.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating Biomarkers in Patients With Colorectal Cancer and Native KRAS Treated With Chemotherapy + Cetuximab — NCT01276379.
- Registry record last updated 2021-07-02; status last verified 2021-06.
- Results first posted 2021-07-02.
- 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
This completed phase 2 study enrolled 221 participants with advanced and/or metastatic colorectal cancer with wild-type KRAS. It was prospective, multicenter, open-label, and single-arm. The treatment was FOLFIRI or FOLFOX-6 with cetuximab, followed by cetuximab monotherapy according to the regimen description.
The primary outcome was median progression-free survival with a 95% confidence interval, assessed using RECIST 1.1 in an evaluable population. The study aimed to assess biomarkers and described groups based on a proposed score, with outcome reporting by BRAF mutation subgroup. The registry record does not report the numerical primary outcome results or the biomarker-group estimates.
Secondary outcomes included overall survival, response duration, adverse events, biomarker analysis, and tumoral response. The record lists serious adverse-event counts and terms, but does not provide a comparative safety assessment. The absence of a randomized control arm limits causal and comparative conclusions.