Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer (NCT00100841), a na phase 2 study. The primary outcome is Severe Adverse Event (SAE) Rate.

2. Clinical Question

This question is about the safety experience observed while participants received the combination, not a comparison of the regimen against another treatment. The listed adverse-event summary includes 54 participants affected by serious adverse events among 66 at risk, and 63 affected by other adverse events among 66 at risk. Those counts describe the posted safety record; they do not by themselves provide a treatment effect relative to a control group.

The listed conditions include several forms and stages of colorectal cancer, while the brief summary describes the intended population as patients with unresectable stage IV colorectal cancer. The registry record does not report further eligibility details or a narrower analysis population for the primary safety question.

3. Trial Design

This was a Phase II, single-group clinical trial sponsored by the National Cancer Institute (NCI). The record lists the study as completed, with enrollment of 66. Allocation is recorded as not applicable and masking as none. There was no parallel control arm, so the study cannot provide a randomized, like-for-like comparison of the combination with another regimen.

The regimen included cetuximab, bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil. The recorded schedule says cetuximab was given intravenously on day 1 in weeks 1-8. Bevacizumab, oxaliplatin, and leucovorin calcium were also given intravenously on day 1, and fluorouracil was given continuously over 48 hours on days 1 and 2 of weeks 1, 3, 5, and 7. The registry description gives the infusion durations for these agents, but the final part of the arm description is incomplete in the record.

The study began in 2004-11 and reached primary completion in 2011-07. Its primary safety timeframe is described as the duration of the study. The registry record does not report a more detailed schedule for safety assessments or follow-up, a protocol-defined control condition, or a separate comparison group. As a single-group study, its safety findings describe events recorded during treatment and follow-up; they do not isolate the effect of the regimen from other causes or establish how outcomes would have differed under another treatment.

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: One patient was enrolled but never started treatment

Overall Study

Analysis population for the primary outcome, as defined in the registry: 66 patients treated with cetuximab

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Severe Adverse Event (SAE) Rate, measured over The duration of the study.

The primary endpoint is titled Severe Adverse Event (SAE) Rate, with the unit recorded as participants. The objective is described as evaluating safety in all treated patients, using a specific definition: grade 5 events, grade 4 hemorrhage or thrombosis, or bowel perforation. The timeframe is the duration of the study. This endpoint therefore focuses on serious or severe safety events defined by their grade or clinical type, rather than on every symptom or laboratory abnormality.

In general, a prespecified safety endpoint helps make clear which events are being counted and which population and observation period the count refers to. A participant-based summary indicates how many participants were affected; it is distinct from a count of repeated events, because one participant may experience more than one event. The registry record does not report a breakdown of the primary endpoint by event type, grade, timing, or number of events per participant.

The posted adverse-event summary lists 54 participants affected by serious adverse events among 66 at risk. The registry record does not provide enough detail to determine how that broad serious-event summary maps onto each category in the primary endpoint definition. It also does not report a separate estimate with a confidence interval or a formal statistical analysis for the primary endpoint. The count is therefore best read as a descriptive safety result, not as a comparative estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Understanding the design is essential to interpreting the safety counts. This is a Phase II, single-group study with no masking and no randomized allocation. In general, a single-group study can describe what happened among people who received a regimen, but it lacks a concurrent control group for separating treatment-related effects from disease, background risk, or other influences. Because there is no randomized comparator, the counts do not estimate a between-treatment difference.

What does a participant count represent?

The primary endpoint is expressed in participants. A participant count records whether people experienced an event or met the endpoint definition; it is not necessarily the number of event episodes. One person can experience multiple events, and the registry record does not report episode-level counts. The posted safety summary lists 54 participants affected by serious adverse events among 66 at risk, and 63 affected by other adverse events among 66 at risk. These reported counts should be kept distinct from the listed percentages for individual serious-event terms, because the record does not specify the percentage denominator or provide corresponding event counts.

Why does the event definition matter?

The primary endpoint definition limits the focus to grade 5 events, grade 4 hemorrhage or thrombosis, or bowel perforation. A definition based on severity and event type makes the intended safety question more specific than a tally of all adverse events. General statistical practice requires interpreting a result according to the prespecified definition and observation period. Here, the registry gives the duration of the study as the timeframe, but does not report a detailed endpoint adjudication process or event-by-event breakdown. The broad serious-event summary should therefore be distinguished from the exact primary endpoint definition.

How should uncertainty be assessed?

In general, a confidence interval conveys the precision of an estimate by showing a range of values compatible with the observed data under the stated statistical model. A narrow interval indicates greater precision than a wide interval, but neither resolves systematic limitations such as selection or lack of a control group. The registry record does not report a confidence interval, standard error, p-value, or formal primary-endpoint analysis. Consequently, statistical precision and evidence against a comparison value cannot be assessed from a reported inferential analysis.

For count outcomes, the statistical model should reflect how the data were collected. If the outcome is whether each participant experienced at least one event, a participant-level binary analysis is conceptually different from an analysis of repeated event counts. General methods for event counts may need to account for over-dispersion, which occurs when variability exceeds what a simple count model expects. That issue matters only when the analysis uses counts of recurrent events; the registry record does not report such an analysis, so no model choice or over-dispersion adjustment can be identified.

What does the planning illustration mean?

In general, sample-size calculations are planning tools: they describe how many participants a hypothetical study might require under specified assumptions. They are not observed power and do not measure the chance that a completed study has demonstrated a treatment effect. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. It is not the design of this single-group study. Any such calculation is a hypothetical planning scenario and cannot turn the observed single-group safety counts into a randomized comparison.

The registry record does not report the trial's own sample-size justification, assumptions for a primary safety analysis, or a formal analysis plan. It also does not report interim analyses, stopping rules, adjustment for covariates, or a statistical model for the endpoint. Those methods cannot be inferred from the Phase II label, the enrollment, or the fact that the study is complete. No formal analyses are listed in the record.

Multiplicity is another general consideration when a study evaluates more than one outcome or performs several statistical tests. Testing multiple hypotheses can increase the chance of a false-positive result unless the analysis plan addresses that issue. The registry lists 2 outcome measures, but it does not report a multiplicity strategy or formal testing results. Since no inferential analyses are listed, there is no reported multiplicity-adjusted or unadjusted primary result to interpret.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, but it does not report a multiplicity plan, a hierarchy of outcomes, or any adjustment for multiple comparisons. In general, multiplicity methods are used when several statistical tests are conducted, because repeated testing can increase the chance of a false-positive finding. The record lists no formal analyses, so it does not establish that such testing occurred or how it would have been handled.

The primary safety population is described as 66 patients treated with cetuximab. The safety summary also lists 66 participants at risk for serious and other adverse events. The registry record does not report a participant flow account, exclusions from the safety analysis, missing outcome counts, or procedures for handling missing safety information. It does not state whether the analysis used an intention-to-treat population or another named analysis population.

These omissions limit assessment of completeness and analytic choices. A count among participants with recorded safety information can be interpreted differently from a result that accounts for all eligible or treated participants, but the record does not describe such details. The reported safety counts remain useful as a description of the posted results, while their handling of missing observations and the relationship to any broader study population are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (22.7%), fatigue (13.6%), diarrhea (13.6%), neuropathy: sensory (12.1%), abdominal pain (9.1%).

The registry lists 54 participants affected by serious adverse events among 66 at risk, and 63 affected by other adverse events among 66 at risk. These are participant counts. They do not indicate how many separate event episodes occurred, and the registry record does not provide a participant-level breakdown by event, grade, or timing.

The primary safety objective defines the events of interest as grade 5 events, grade 4 hemorrhage or thrombosis, or bowel perforation. The record does not itemize the posted serious-event count against those categories, so the broader serious-event summary cannot be interpreted as a detailed breakdown of the primary endpoint. Deaths are not reported in the registry record.

The listed serious-event terms and percentages are neutropenia (22.7%), fatigue (13.6%), diarrhea (13.6%), sensory neuropathy (12.1%), abdominal pain (9.1%), and acne/acneiform rash (7.6%). The denominator for these percentages is not reported in the registry record. They describe the terms listed in the safety summary, not comparative risks. With no control group, these data do not show whether the observed event experience was higher or lower than it would have been under another treatment.

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

The findings document a safety experience for a single group treated with cetuximab, bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil. The registry lists serious and other adverse-event participant counts, along with selected serious-event terms and percentages. These descriptions may help readers understand which safety events were recorded during the study, but they do not provide a controlled estimate of the regimen's effect on safety.

The result does not establish that the treatment caused each event. In an uncontrolled study, adverse events can arise from the underlying cancer, other health conditions, concomitant care, or treatment. The record does not provide information that would separate these possible sources. Nor does it show how the safety profile compares with a different regimen, because there is no comparator arm.

The primary endpoint is defined around a selected set of severe events, but the record does not give a component-level analysis, confidence interval, or formal statistical test. The serious-event summary is a descriptive count, and the individual terms are reported with percentages whose denominator is not specified. Thus the results do not quantify statistical precision or support conclusions about comparative safety.

The registry identifies the trial as Phase II and completed, with enrollment of 66. Those design and status details do not supply a sample-size justification, establish that the study had adequate precision for its safety objective, or substitute for an analysis plan. The record also does not report missing-data handling or a detailed account of the analysis population. The most defensible interpretation is therefore limited to what was recorded: adverse events were reported among treated participants, with the listed counts and terms, while comparative and causal conclusions remain unsupported by this study design and reporting.

13. Why This Trial Matters Statistically

Statistically, this trial illustrates the difference between describing a treatment group's experience and estimating a treatment effect. The single-group design supports a descriptive account of adverse events among treated participants. It does not create a randomized contrast, so a reader cannot attribute differences in outcomes to the regimen by comparing study arms or estimate what would have happened under an alternative treatment.

The registry also makes the definition of the primary safety outcome important. The endpoint focuses on grade 5 events, grade 4 hemorrhage or thrombosis, or bowel perforation, while the posted safety summary includes a serious-event category and selected event terms. Without component-level reporting, readers cannot fully connect the broad summary count to each element of the defined endpoint. This is a reporting issue as well as an analytic one: clear definitions and detailed results are needed to evaluate whether the reported summary answers the stated question.

Another statistical lesson is that counts and percentages need clear denominators and uncertainty measures. The record reports participant counts for broad adverse-event categories and percentages for selected terms, but does not specify the percentage denominator or report confidence intervals for the primary endpoint. A point estimate alone does not communicate how precisely a safety frequency has been estimated. These limitations do not erase the descriptive information; they bound the conclusions that can be drawn from it.

Finally, a hypothetical planning calculation is not the same as the design or analysis of the completed trial. The stated planning assumptions describe a two-arm scenario, whereas this study is single-group. Keeping those roles separate prevents planning illustrations from being mistaken for observed evidence or for the trial's own sample-size rationale, which is not reported in the registry record.

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 design limitation is the absence of a comparator. Because the study is single-group and not randomized, the posted adverse-event experience cannot be contrasted with a control regimen or interpreted as a causal difference. The lack of masking is also recorded; the registry does not report whether or how this affected safety-event ascertainment.

Reporting of the primary safety outcome is limited. The record defines the endpoint but does not provide a component-level breakdown, an inferential analysis, or a confidence interval. It does not report event timing, repeated-event counts, adjudication procedures, or how the serious-event summary relates to the endpoint's specified grades and event types. The denominator for the listed individual serious-event percentages is not reported in the registry record.

The registry record does not report missing-data handling, participant flow through treatment and follow-up, exclusions from the safety population, or the analysis population beyond the description of treated patients. It also does not report an analysis plan, sample-size justification, interim analyses, stopping rules, or multiplicity procedures. These details cannot be inferred from the study phase or completion status.

The arm description ends with an incomplete final phrase, so that part of the regimen documentation is not available in the registry record. The trial's stated population is patients with unresectable stage IV colorectal cancer, while the condition list includes several colorectal cancer diagnoses; further eligibility details are not reported. These design and reporting limits mean the findings are best treated as a descriptive record of safety events, not a complete or comparative assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Trial of FOLFOX6, Bevacizumab and Cetuximab in Patients With Colorectal Cancer — NCT00100841.
• Registry record last updated 2015-07-27; status last verified 2013-07.
• Results first posted 2015-07-27.
• 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

This completed Phase II trial was a single-group study sponsored by the National Cancer Institute (NCI), with enrollment of 66. It evaluated cetuximab and bevacizumab combined with oxaliplatin, leucovorin calcium, and fluorouracil in the context of stage IV colorectal cancer that could not be removed by surgery. Allocation was not applicable, masking was none, and there was no control arm.

The primary objective was safety, with serious adverse events defined as grade 5 events, grade 4 hemorrhage or thrombosis, or bowel perforation over the duration of the study. The registry lists 54 participants affected by serious adverse events among 66 at risk and 63 affected by other adverse events among 66 at risk. It does not report a formal analysis, confidence interval, detailed endpoint breakdown, missing-data approach, or comparative result. The findings therefore describe the posted safety experience but do not estimate a causal or comparative treatment effect.