Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors (NCT00599924), a non-randomized phase 1 study. The primary outcome is Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

This was a Phase I, non-randomized, single-group study sponsored by Pfizer. The registry lists an enrollment of 53 and a completed status. The study started in 2005-09, with primary completion in 2008-11. It enrolled people with advanced solid malignancies, including colorectal cancer, and tested sunitinib in combination with FOLFOX.

The brief summary describes three sunitinib dosing schedules with a starting dose of 37.5 mg/day: Schedule 2/2, Schedule 4/2, and continuous dosing. The adverse-event listings distinguish seven regimen groups, including groups using 37.5 mg, 50 mg, or 25 mg sunitinib, with modified FOLFOX6. One group is identified as colorectal cancer only. These are treatment-regimen groups within a non-randomized study, not randomized comparison arms.

The registry records no masking. A single-group design without random allocation can describe observed outcomes under the regimens studied, but it does not by itself separate treatment effects from changes due to patient characteristics, disease course, or other influences. Comparisons across regimen groups also require caution because the record does not establish that the groups were formed to be comparable or that their results were analyzed as controlled contrasts.

The primary endpoint was the number of subjects with adverse events and serious adverse events up to 20 weeks. The registry describes the primary population as enrolled subjects who received at least one dose. It also notes replacement of subjects who did not complete follow-up for dose-limiting toxicity assessment because of death from progressive disease or other non-treatment-related events. Further details about the allocation process, dose-selection procedure, and statistical plan are not reported in the registry record.

4. Participant Flow and Accounting

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

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) = all subjects enrolled in the study that received at least one dose of study medication. Subjects who did not complete the follow-up period for dose limiting toxicity assessment because of death from progressive disease or other non-treatment related events were replaced.

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over up to 20 weeks.

The primary endpoint counts participants with adverse events (AEs) and serious adverse events (SAEs) during follow-up up to 20 weeks. The registry says that all observed or volunteered AEs and SAEs were reported, regardless of treatment group or suspected causal relationship to the investigational product. This makes the endpoint a broad safety description, rather than a count limited to events judged to have been caused by sunitinib or FOLFOX.

Counting participants with at least one event gives a straightforward description of how many people in each listed regimen group experienced an event. It differs from counting the total number of event episodes: a participant may have more than one event, while the participant-level count records whether that person had an event. The registry outcome is explicitly framed as the number of subjects, and the posted results distinguish those with serious events from those with other adverse events.

Seriousness and severity are not interchangeable concepts. In general, seriousness classifies an event using regulatory criteria, while severity describes its intensity. The registry lists serious adverse events separately; it does not provide a severity grading scale in the endpoint description. The endpoint is useful for describing safety observations during the stated follow-up, but without a randomized comparator it cannot establish how event frequency would differ under another treatment or without the study regimen.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The central statistical feature is that the registered primary result is a set of participant counts, not a comparative treatment-effect estimate. Each regimen listing identifies an at-risk count and a count of participants affected by serious or other adverse events. Such counts are directly interpretable as descriptions of the observed study groups. They do not, on their own, answer whether an event rate differs from what would have occurred under another regimen or in the absence of treatment.

What does a participant count represent?

A participant-level event count treats each person as affected or not affected for the outcome being counted. It is distinct from the number of event episodes: a person with repeated events still contributes as a participant with an event, while an episode-level summary would count repetitions separately. The registry’s primary outcome is titled as the number of subjects with AEs and SAEs. It does not provide episode counts in the information.

The at-risk count defines the group against which the affected count is read. For example, an entry with 9 at risk and 4 affected means that the registry lists 4 participants with the specified outcome among 9 at risk in that regimen group. This remains a descriptive observation. It should not be converted into an unadjusted treatment comparison or treated as a causal estimate.

Why is random allocation important?

In general, random allocation helps balance measured and unmeasured participant characteristics between treatment groups, making comparisons less vulnerable to systematic differences at baseline. This study is recorded as non-randomized, and the registry identifies it as a single-group study. The regimen groups therefore cannot be assumed to be exchangeable. Differences in their observed counts might reflect differences in participants, disease status, treatment schedule, follow-up, or other factors, as well as any treatment-related differences. The registry does not report an analysis that adjusts for such factors.

Even if groups have different observed counts, the size of a difference is not enough to establish a reliable contrast. In general, statistical uncertainty depends on the amount of information in the groups and the variation in the outcome. Confidence intervals communicate a range of values compatible with the data under a specified statistical model; they do not remove design bias or prove causation. Confidence intervals for the adverse-event counts are not reported in the registry record.

What can significance testing add?

A statistical test can assess how compatible observed data are with a specified null hypothesis, given the model and assumptions used. A p-value is not the probability that the null hypothesis is true, nor does it quantify clinical importance. In this study, no analyses are listed for the outcome record, and comparative test results are not reported in the registry record. It would be inappropriate to infer statistical significance from the raw counts or to treat the regimen labels as randomized arms.

The record’s sample-size assumptions describe 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. Such calculations are planning illustrations, not observed power. The equal-allocation two-arm premise does not match the reported non-randomized, single-group design, so those assumptions cannot turn the observed regimen-group counts into a valid randomized comparison. Numerical planning results are not reported in the registry record.

How should event-term percentages be read?

The serious-event terms are accompanied by percentages, including disease progression (33.3%), sepsis (25.0%), pyrexia (22.2%), abdominal pain (16.7%), anorexia (16.7%), and dehydration (16.7%). In general, a percentage depends on its denominator and on whether it counts participants, events, or another unit. The denominator and calculation basis for these percentages are not reported in the registry record. These percentages should be quoted as registry values, without converting them into rates or comparing them directly with the group-level participant counts.

Over-dispersion is a general issue when event counts vary more than a simple statistical model expects; it can make conventional uncertainty estimates too narrow if the model does not account for that extra variability. Here, the primary outcome is reported as participant counts, and the registry record does not specify an over-dispersion model or a model-based analysis. No such modeling should be inferred from the counts.

What is the role of pharmacokinetic outcomes?

Pharmacokinetic measures describe drug concentration over time. In general, Cmax is a maximum concentration measure, Tmax is the time to that maximum, Cmin is a minimum concentration measure, clearance describes drug removal in relation to concentration, AUC24 summarizes exposure over a stated time interval, and terminal phase half-life describes the decline during the terminal phase. These are distinct from clinical event counts. The registry lists these measures as secondary outcomes, but their numerical results are not reported in the registry record.

Overall, the available statistical information supports a descriptive reading of adverse-event counts and event terms. It does not report uncertainty intervals, adjusted comparisons, statistical tests, or a comparative estimate for the regimens. General statistical methods cannot compensate for missing outcome details or the absence of random allocation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 30 outcome measures, including the primary adverse-event outcome, objective response, and multiple pharmacokinetic measures. Examining many outcomes can raise a multiplicity concern: in general, the more separate hypotheses tested, the greater the chance of observing an apparently notable result by chance if no adjustment or prespecified interpretation strategy is used. The registry record does not report a multiplicity adjustment, a hierarchy for interpreting outcomes, or a statistical analysis plan. It also lists no analyses for the outcome record. This does not establish that no analyses were conducted; it means they are not reported in the registry record.

The available endpoint description identifies an intent-to-treat population as all enrolled subjects who received at least one dose of study medication. It also says that subjects who did not complete follow-up for dose-limiting toxicity assessment because of death from progressive disease or other non-treatment-related events were replaced. That replacement statement is relevant to understanding how participants were handled for dose-limiting toxicity assessment, but it does not fully describe missing-data handling for the primary adverse-event endpoint or the secondary outcomes.

Missing outcome data can affect interpretation if the reason for missingness is related to health status, treatment, or the chance of experiencing an event. In general, transparent reporting describes how much information is missing, why it is missing, and what assumptions are used to analyze it. Those details, along with the number assessed for each outcome and the handling of incomplete follow-up, are not reported in the registry record. The replacement clause should not be taken to mean that missingness was absent or that replacement participants were included in every analysis in a particular way.

The record does not report interim analyses, prespecified stopping rules, or a sample-size justification. Those aspects of the statistical plan are therefore 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (33.3%), sepsis (25.0%), pyrexia (22.2%), abdominal pain (16.7%), anorexia (16.7%).

For each listed regimen, the serious adverse-event result gives the at-risk count and the number affected. Read the pair as the observed participant count in that regimen group, not as a comparison with a control group. For example, the 37.5 mg Sunitinib + Modified FOLFOX6 (Schedule 4/2) group lists 12 at risk and 7 affected by serious adverse events. The 50 mg Sunitinib + Modified FOLFOX6 (CRC Only, Schedule 2/2) group lists 5 at risk and 0 affected. The other regimen-specific counts are also descriptive.

The registry separately lists all participants at risk as affected by other adverse events in each regimen group. This tells the reader that at least one other adverse event was recorded for each listed participant, not how many events each person had or how severe they were. The outcome definition includes events irrespective of whether investigators suspected a causal relationship to the study drugs. Therefore, the counts should not be treated as counts of events proven to be caused by treatment.

The term percentages for serious events use a denominator that is not reported in the registry record. They should be read as reported rather than interpreted as risks among all enrolled participants. Death counts are not reported in the registry record. Neither a zero serious-event count in a group nor the absence of a reported death count establishes that no safety concern occurred.

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

The registry results describe adverse events observed among participants receiving sunitinib with modified FOLFOX6 under the listed schedules and doses. They document participant counts for serious and other adverse events and identify several serious-event terms with reported percentages. This is useful descriptive information about what was recorded during the study’s safety follow-up, which was defined as up to 20 weeks.

The results do not establish that sunitinib plus FOLFOX caused every event. The primary endpoint included all observed or volunteered AEs and SAEs regardless of suspected causal relationship. The counts also do not show that an event was absent simply because no participant in a particular group was recorded as affected. Small counts and the lack of reported uncertainty estimates limit how precisely the underlying event frequency can be characterized.

The study does not provide a randomized control comparison. As a result, the observed counts cannot establish that one listed schedule or dose produces fewer adverse events than another, nor can they determine what would have happened under a different treatment. Differences between regimen groups may reflect factors other than regimen. No comparative analysis, confidence interval, or treatment-effect estimate is reported in the registry record.

The study’s stated aim included determining the maximum tolerated dose and assessing safety. The adverse-event information is relevant to that aim, but these counts alone do not identify a dose as the maximum tolerated dose. Dose-limiting toxicity criteria, the dose-selection process, and the results needed to describe a selected dose are not reported in the registry record. The listed secondary outcomes also include objective response and pharmacokinetic measures, but their results are not reported in the information analyzed.

The appropriate conclusion is limited to the observed registry descriptions: adverse events were recorded in the listed regimen groups, and the counts and serious-event terms are not causal or comparative estimates. They should not be interpreted as proof of benefit, absence of harm, or superiority of any regimen.

13. Why This Trial Matters Statistically

This trial illustrates why design and statistical interpretation must be considered together. The registry lists multiple sunitinib schedules and doses with modified FOLFOX6, but records the study as non-randomized and single-group. Regimen-specific counts can show what was observed within each group; they cannot create a controlled comparison when participants were not randomly allocated to comparable groups.

It also highlights the importance of clarifying what an endpoint counts. A participant-level count of people with an event is not the same as a total number of event episodes. Serious events are reported separately from other adverse events, while event-term percentages have a calculation basis that is not stated in the registry record. Clear denominators and definitions are essential for readers to understand the scale and meaning of safety results.

The registry’s primary outcome applies a broad event definition, including observed or volunteered events regardless of suspected causal relationship. That breadth is useful for describing safety observations, but it makes it especially important not to read the counts as proof of drug causation. Separating the description of events from causal interpretation is a central statistical discipline.

Finally, the record lists numerous outcomes but does not report analyses, uncertainty intervals, a multiplicity approach, or detailed missing-data methods. These omissions limit the precision and inferential claims readers can make. The study can still inform a descriptive account of the regimens and safety observations recorded, while its design and reporting constrain comparisons and generalization.

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 principal limitation for interpreting the adverse-event counts is the non-randomized, single-group design. The regimen listings are not a randomized comparison, and the registry itself cautions that the groups are not like-for-like controls. Participant differences and other influences may therefore contribute to the observed variation between groups.

The adverse-event group counts are small, and the registry record does not report confidence intervals or other measures of uncertainty for them. The serious-event term percentages are reported without a stated denominator or calculation basis. Death counts are not reported in the registry record. The endpoint includes events regardless of suspected causality, and the information does not provide event-level details such as duration or severity grading.

The primary population definition includes enrolled participants who received at least one dose. The record also describes replacement of subjects who did not complete follow-up for dose-limiting toxicity assessment because of death from progressive disease or other non-treatment-related events. It does not fully explain how this replacement policy relates to analysis of the adverse-event endpoint, or how incomplete follow-up and missing data were handled for each outcome.

The registry lists 30 outcome measures, but the statistical analysis plan, multiplicity handling, interim analyses, and sample-size justification are not reported in the registry record. Although objective response and pharmacokinetic outcomes are listed, their numerical findings are not included in the information analyzed. These reporting limits mean that conclusions should remain focused on the posted descriptive safety counts rather than comparative or causal claims.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors — NCT00599924.
• Registry record last updated 2015-07-15; status last verified 2015-06.
• Results first posted 2009-12-09.
• 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

NCT00599924 is a completed Phase I study sponsored by Pfizer, titled Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors. The official title describes a study of SU011248 with oxaliplatin, leucovorin, and 5-fluorouracil in advanced solid malignancies. The registry records non-randomized allocation, no masking, a single-group model, and enrollment of 53. The listed dates are study start in 2005-09 and primary completion in 2008-11.

The study assessed sunitinib combined with modified FOLFOX6 across several dose and schedule groups. The primary outcome counted participants with adverse events and serious adverse events up to 20 weeks. Posted results include regimen-specific participant counts and serious-event terms, while the record does not report comparative analyses, uncertainty intervals, or detailed missing-data methods. The findings are best read as descriptive observations within a non-randomized Phase I study.