First-Line FOLFOX-Bevacizumab for Advanced Colorectal Cancer With Wild-Type Ras: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First-Line FOLFOX-Bevacizumab for Advanced Colorectal Cancer With Wild-Type Ras (NCT01057017), a na phase 2 study. The primary outcome is Number of Patients With Toxicity to Combination of Panitumumab and Bevacizumab.

2. Clinical Question

The registry record concerns maintenance treatment after first-line FOLFOX-bevacizumab for patients with advanced colorectal cancer with wild-type Ras. Its primary objective was to determine the safety of panitumumab and bevacizumab given every 3 weeks as maintenance therapy for patients with metastatic colorectal cancer. The primary outcome is the number of patients with toxicity to the combination, assessed using CTCAE version 3.

This is a safety-focused question, not a randomized comparison of maintenance strategies. The registry record does not report a control group or an efficacy comparison. The posted results therefore describe participants in the intervention group; they cannot establish how outcomes would compare under another treatment or no maintenance treatment.

3. Trial Design

This is a phase 2, single-group study listed as terminated. The registry record lists enrollment as 5, allocation as NA, and masking as none. Its title identifies first-line FOLFOX-bevacizumab and maintenance with panitumumab and bevacizumab for advanced colorectal cancer with wild-type Ras. The brief summary describes maintenance therapy until disease progression.

The treatment descriptions are not entirely uniform. The brief summary lists bevacizumab at 7.5mg/kg and panitumumab at 9mg/kg, administered every 3 weeks. The arm description also lists bevacizumab at 7.5mg/kg, and gives panitumumab Dose Level 1 at 6mg/kg and Dose Level 2 at 9mg/kg. Infusion durations also differ between the summary and arm description. The registry record does not explain these differences, so the descriptions should not be treated as evidence of which dose or infusion duration each participant received.

The record lists one outcome measure and no analyses. The primary outcome is the number of patients with toxicity to the combination, with assessment every 3 weeks until a patient comes off study for progressive disease, for up to 2 years. CTCAE version 3 is named for toxicity assessment. No more detailed assessment schedule, eligibility criteria, dose-assignment procedure, or account of treatment exposure is reported in the registry record.

The study is not a like-for-like control comparison: there is one intervention group and no separate comparator arm. The registry status is terminated, but the reason for termination is not reported in the registry record. The record also does not explain whether termination affected recruitment, follow-up, or outcome reporting. With a listed enrollment of 5 and no analyses reported, the posted safety counts should be read as a limited descriptive account, not as a comparative estimate.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

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 Number of Patients With Toxicity to Combination of Panitumumab and Bevacizumab, measured over every 3 weeks until patient comes off study (progressive disease), for up to 2 years.

The primary endpoint is the number of patients with toxicity to the combination of panitumumab and bevacizumab. The registry identifies CTCAE version 3 as the toxicity assessment standard and gives a timeframe of every 3 weeks until a patient comes off study for progressive disease, for up to 2 years. This endpoint is intended to describe whether participants experienced toxicity during maintenance treatment.

A participant-level count can make the safety result easier to interpret than a list of every recorded symptom alone: it indicates how many people were recorded as having toxicity, rather than how many times a symptom was noted. However, the registry record does not state a toxicity threshold for the primary endpoint, explain how multiple toxicities in one participant were handled, or provide a full endpoint definition beyond the stated title and description. It also does not report the severity grading rules beyond naming CTCAE version 3.

The posted result includes adverse-event summaries, but the registry record does not report an inferential analysis for the primary endpoint. The outcome is therefore best understood as a descriptive safety count in this study group. It does not estimate a treatment effect relative to a comparator, and the record does not establish whether the reported events were caused by either treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcome is a count of participants with toxicity, so the basic result is descriptive: it records how many participants were classified as having an event. Descriptive counts can communicate what was observed in a study group, but they do not on their own quantify a causal treatment effect. A comparative effect requires a meaningful comparison, and the registry identifies a single group without a separate control arm.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under specified assumptions. It helps distinguish an estimate that is precise from one that remains compatible with a wide range of values. A count alone does not show this uncertainty, and an interval does not resolve design limitations such as the lack of a comparator. No confidence interval for the primary endpoint is reported in the registry record.

For a binary participant-level outcome, an analysis may treat each person as either having or not having the outcome under a defined observation period. That requires a clear definition of the event and the population being analyzed. Here, the registry names the outcome as the number of patients with toxicity and names CTCAE version 3, but does not report a detailed threshold, a full event-aggregation rule, or an analysis population. The adverse-event fields provide counts, but the record does not explain how those counts were translated into a primary-endpoint estimate.

Why does the study design matter?

A single-group study can describe what happened among participants who received the intervention. Without a concurrent comparator, it cannot separate treatment-related effects from other explanations for observed outcomes. This matters especially for safety: an event observed during treatment is not necessarily caused by treatment. A randomized comparison can support a different kind of inference by balancing groups under the study design, but this registry record does not describe such a comparison.

The allocation field is listed as NA and the study model as single group. No masking is reported. These features do not establish that the safety observations are biased, but they limit what can be inferred from the design. The record does not provide information about independent event adjudication or other procedures that might affect event classification.

How should repeated assessments be understood?

The endpoint timeframe says assessment every 3 weeks until a patient comes off study for progressive disease, for up to 2 years. In general, repeated safety assessments can capture events that arise at different points during treatment. They also raise analytic questions: whether an outcome means any event during follow-up, the first event, or a count of repeated events; how events are grouped by participant; and how differing lengths of follow-up are handled. The registry record does not report these details. The displayed participant counts and event-term counts should therefore be kept distinct rather than combined into a new summary.

Over-dispersion is a general issue for count data when variability exceeds what a simple count model assumes. It can matter when analyzing repeated event counts, particularly if some participants experience many events while others experience few. The primary endpoint is described as a participant count, not as a repeated-event rate, and the registry record does not report a model for event counts. There is therefore no basis in the record for stating that over-dispersion was assessed or addressed.

What does the analysis record tell us?

The registry lists one outcome measure and no analyses. It does not report a statistical test, an effect estimate, a confidence interval, a model, or an adjustment procedure. That absence means the posted result should be read as a descriptive registry result, not as a test of a prespecified statistical hypothesis. The registry record does not report whether analyses were planned but not posted, or whether the study ended before any analysis was conducted.

The sample-size assumptions describe planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. Those assumptions describe illustrations, not the design or outcome of this single-group study. The record does not report a two-arm comparison from which to interpret such illustrations as a trial result. Planning sample sizes are not observed power, and no conclusion about the adequacy of the original design or recruitment target follows from them.

What can be concluded from the posted counts?

The adverse-event figures document events as recorded in the registry, but the available information does not provide the detail needed to estimate the uncertainty of a treatment-related risk or compare risks across treatments. A more complete analysis would ordinarily need a defined analysis population, endpoint rules, follow-up information, and a suitable comparator or a clearly stated descriptive objective. Whether these elements were available to the investigators is not reported in the registry record. Interpretation should remain within what is recorded: a small single-group safety experience, with no posted statistical analysis.

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("Panitumumab and Bevacizumab")
n      <- c(5)
events <- c(1)
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  Panitumumab and Bevacizumab  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a multiplicity strategy, such as how multiple outcomes or statistical tests would be handled. Because no inferential analyses are listed, the record does not establish that hypothesis tests were conducted or that any adjustment for multiple testing was needed or applied.

Missing-data handling is not reported in the registry record. The endpoint timeframe allows follow-up until a patient comes off study for progressive disease, for up to 2 years, but the registry does not state how incomplete follow-up, missed assessments, or discontinuation for other reasons were handled. It also does not report the number of participants with complete endpoint data or whether any observations were excluded.

The analysis population is not reported in the registry record. In general, an analysis population defines which participants contribute to an estimate and under what rules. The enrollment count alone does not identify the population used for the posted adverse-event summaries or confirm that every enrolled participant had the same length of observation.

The record does not state whether an intention-to-treat, treated-participant, or other analysis population was used. Nor does it specify how participants who changed dose, stopped treatment, or had incomplete toxicity assessments would be counted. These omissions limit interpretation of the event counts, particularly when follow-up can continue until progression or for up to 2 years.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anorexia (3), nausea(3), vomiting(2), weakness(3), confusion(1), hypok(3), hypophos(3), hypoca(3) (20.0%).

The adverse-event summary reports 1 participant with a serious adverse event among 5 at risk, and 5 participants with other adverse events among 5 at risk. These are distinct registry summaries; the record does not explain whether the categories overlap or how they relate to the primary toxicity endpoint. No additional total should be constructed from them.

The serious-event terms are listed as anorexia (3), nausea (3), vomiting (2), weakness (3), confusion (1), hypok (3), hypophos (3), and hypoca (3). The accompanying 20.0% is not defined further in the registry record. It should not be assumed to represent a percentage of participants with any particular term, since the denominator and calculation are not explained.

Event-term counts are not necessarily participant counts. A participant may have more than one reported term, and the record does not describe the counting rules or timing of events. The listed counts should therefore be read as the registry's reported terms and counts, not as a breakdown into mutually exclusive groups.

These figures describe safety observations in a single intervention group. They do not establish causation or allow a comparison with another treatment. The registry record does not report event severity by term, exposure-adjusted rates, or a detailed account of how seriousness was classified.

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

The result establishes what the registry records for a small, single-group safety study: the adverse-event summary lists 1 participant with a serious adverse event and 5 with other adverse events. The registry also lists serious-event terms and counts. The primary endpoint is described as the number of patients with toxicity to the combination, assessed using CTCAE version 3.

These observations do not establish that panitumumab or bevacizumab caused a particular event. Events occurring during treatment may have other explanations, and this study does not include a comparator group that could help distinguish treatment-associated risk from background risk. The record also does not report a statistical analysis or an uncertainty interval for the primary endpoint.

The result does not establish comparative safety. There is no separate control arm, and allocation is listed as NA. It also does not answer whether the maintenance combination improves tumor response, delays progression, or changes survival: those outcomes are not reported as results in the registry record.

The study's terminated status is relevant context, but the record does not state why it was terminated or how termination affected follow-up and data collection. It cannot be assumed that termination was caused by safety concerns, lack of efficacy, recruitment difficulty, or any other specific reason.

General statistical interpretation requires attention to the number of observations, the endpoint definition, follow-up, and design. With enrollment listed as 5, the counts describe a limited study experience and do not provide a precise estimate of what would occur in a broader population. This is not evidence that an unobserved outcome would be better or worse; it is a limit on what can be inferred from the posted information.

Accordingly, the posted results are best treated as descriptive registry data. They document reported adverse events in the intervention group, but do not support a claim about treatment benefit, comparative risk, or the cause of individual events.

14. Why This Trial Matters Statistically

This record illustrates the difference between a safety objective and a comparative treatment question. Its stated primary objective is to determine the safety of every-3-week panitumumab and bevacizumab maintenance. The registry identifies a single group and does not describe a control arm, so the result is a description of events among participants rather than an estimate of how safety differs between treatment strategies.

It also shows why the endpoint definition and event summaries need to be read separately. The primary outcome is the number of patients with toxicity, while the adverse-event summary lists serious and other events and gives term counts. The record does not explain how these summaries map to the primary endpoint or how repeated terms were handled. A count of participants and a count of reported terms answer different descriptive questions.

The enrollment of 5 and terminated status frame the limited scope of the posted experience. The registry does not report why the study ended or what effect termination had on follow-up. Without that information, readers should not infer a reason for termination or assume that every participant had identical observation time.

Finally, the record distinguishes trial results from planning illustrations. Assumptions such as equal allocation between two arms belong to planning calculations, not to this single-group trial's reported design. Statistical planning quantities cannot replace an observed comparative analysis, and sample-size illustrations are not observed power. Keeping these distinctions clear prevents descriptive safety counts from being overstated as causal or comparative 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.

Several trial-specific limitations constrain interpretation. The registry describes a single group, with allocation listed as NA and no masking. No comparator is reported, so the posted event counts cannot estimate a difference in safety between treatment strategies. The record lists enrollment as 5, which limits the amount of safety experience represented.

The study is listed as terminated, but the reason and timing of termination are not reported in the registry record. Recruitment details, completion status, and the extent of follow-up are also not reported. The endpoint timeframe extends to coming off study for progressive disease, for up to 2 years, but actual participant follow-up is not given.

Treatment details are inconsistent across the registry descriptions. The summary lists panitumumab at 9mg/kg, whereas the arm description gives Dose Level 1 at 6mg/kg and Dose Level 2 at 9mg/kg. The bevacizumab infusion duration also differs between descriptions. The record does not explain which regimen participants received or how dose levels were assigned.

The primary outcome definition is limited, and the record does not report detailed rules for classifying toxicity, handling multiple events, or aggregating repeated assessments. The serious-event list includes abbreviated terms, and the percentage shown with that list is not explained. Missing-data procedures, analysis populations, and statistical analyses are not reported. These limitations leave the safety counts descriptive and prevent a more complete assessment of their precision or comparability.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: First-Line FOLFOX-Bevacizumab for Advanced Colorectal Cancer With Wild-Type Ras — NCT01057017.
• Registry record last updated 2020-02-17; status last verified 2020-02.
• Results first posted 2013-11-04.
• 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

NCT01057017 is a phase 2 registry record for a single-group study of panitumumab and bevacizumab maintenance after first-line FOLFOX-bevacizumab in advanced colorectal cancer with wild-type Ras. The record lists Brown University as sponsor, enrollment of 5, and status as terminated. Start is listed as 2010-01 and primary completion as 2011-04.

The primary outcome is the number of patients with toxicity to the combination, assessed using CTCAE version 3 every 3 weeks until coming off study for progressive disease, for up to 2 years. The adverse-event summary lists 1 participant with a serious adverse event and 5 with other adverse events. No analyses are reported. The registry record does not give the reason for termination, a comparator group, or a statistical analysis of the safety outcome.