Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer (NCT00555672), a non-randomized phase 1 study. The primary outcome is Number of Participants With First-cycle Dose Limiting Toxicities (DLTs).

2. Clinical Question

The clinical question is primarily about dose tolerability in an early-phase study, rather than a comparative estimate of treatment benefit. The primary endpoint counts participants with first-cycle dose-limiting toxicities (DLTs), with DLT incidence assessed during the 21-day cycle. The registry describes the study purpose as determining a safe and tolerable sunitinib dose when combined with cisplatin and 5-fluorouracil.

The record also lists pharmacokinetic outcomes for the drugs and the number of participants with objective response. Those outcomes broaden the study’s descriptive scope, but they do not create a randomized comparison. The registry record does not report the primary DLT count, so the recorded aim can be identified but the primary endpoint result cannot be assessed from the available information.

3. Trial Design

This is a phase I, nonrandomized, unmasked, single-group study registered as NCT00555672. The registry lists enrollment as 34 and status as completed. Pfizer is the sponsor. The condition is stomach neoplasms, and the study title identifies advanced gastric cancer as the clinical setting.

Participants received sunitinib in combination with cisplatin and 5-fluorouracil. The registry lists a group receiving sunitinib 25 mg and a group receiving sunitinib 37.5 mg, each with cisplatin and 5-FU. The record does not describe random allocation to these dose groups. They should therefore be read as dose groups within a nonrandomized study, not as randomized treatment and control arms.

The primary outcome is the number of participants with first-cycle DLTs, assessed over Cycle 1 (Baseline to Day 21). The stated primary population is enrolled participants who received at least one dose of study drug. Listed secondary outcomes include plasma concentration and exposure measures, pharmacokinetic measures for 5-FU, and the number of participants with objective response.

The registry record does not report further details about how participants entered a dose group, whether dose escalation followed a specified rule, or how decisions about dose selection were made. Such details should not be inferred from the phase designation or from the presence of dose groups. Because the design has no randomized comparator, differences between the reported groups cannot be attributed to dose alone without accounting for how participants came to receive each dose.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety: enrolled participants who received at least 1 dose of study drug.

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 Participants With First-cycle Dose Limiting Toxicities (DLTs), measured over Cycle 1 (Baseline to Day 21).

The primary endpoint is the number of participants with first-cycle dose-limiting toxicities. A DLT is an outcome used in early-phase research to identify treatment-related toxicities considered important to dose evaluation. The registry describes the endpoint as the incidence of DLTs assessed during the first cycle, which runs from baseline to Day 21.

Counting affected participants gives a direct description of how often the defined event occurred in the endpoint population. For interpretation, the count needs its denominator: a count by itself does not show the proportion of the relevant participants affected. The registry identifies the safety population as enrolled participants who received at least one dose of study drug, but the primary DLT result itself is not reported in the registry record.

General statistical context: early-phase dose evaluation often uses toxicity observations to inform decisions about doses for further study. That role is distinct from demonstrating comparative efficacy. A DLT count also depends on the operational definition of DLT and the assessment rules used during the cycle. Those detailed definitions and rules are not reported in the registry record, so the endpoint’s broad purpose is clear while its full adjudication criteria cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: a count endpoint records how many participants experienced an event. For a binary outcome such as presence or absence of a DLT, each participant contributes an event status for the specified assessment period. The count is interpretable alongside the number of participants assessed and the population definition. The registry specifies the primary population as enrolled participants who received at least one dose of study drug, but it does not report the primary DLT count or a complete endpoint analysis.

What does an uncertainty interval add?

General statistical context: a confidence interval expresses the uncertainty around an estimated quantity under a stated statistical model. It gives a range of values compatible with the data and assumptions; it is not a guarantee that the true value falls within that range. For event counts, uncertainty depends on both the observed event count and the number of participants assessed. The registry record does not report a confidence interval for the primary endpoint or the listed serious-event counts. Precision therefore cannot be judged from the event counts alone.

Why does the design matter?

The registry describes a nonrandomized, unmasked, single-group study, with sunitinib groups at 25 mg and 37.5 mg alongside cisplatin and 5-FU. General statistical context: random allocation helps balance measured and unmeasured characteristics across comparison groups on average. Without randomization, differences between dose groups may reflect participant selection, clinical circumstances, or other factors as well as dose. The record does not describe an adjusted analysis that would address such differences. The groups are not a randomized control comparison, so their event counts should be presented descriptively rather than as evidence of a causal dose effect.

What can a planning calculation establish?

The record characterizes sample-size calculations as planning illustrations based on an observed effect, not as the trial’s own design. It states assumptions of a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. General statistical context: a planning calculation estimates the sample size that would be needed under its assumptions to detect a specified effect with a chosen operating characteristic. It does not describe the precision or success of the completed study, and it is not observed power. The registry record does not report a sample-size justification for this phase I study. The primary DLT result is also not reported, so the observed effect underlying any such illustration cannot be evaluated from the registry information.

A normal approximation is a mathematical simplification used in some planning calculations. Its adequacy depends on the outcome, event frequency and sample size. General statistical context: when event counts are sparse, approximations may be less reliable, and exact methods or methods tailored to the outcome may be considered. The registry record does not identify the method used for inference on the primary endpoint, so no particular inferential procedure should be attributed to this study.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when outcome variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and uncertainty can be understated. This issue can arise in some count-data settings, but the primary endpoint is described as a participant count for a binary event. The registry record does not identify a model for the endpoint or report evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was used.

The listed pharmacokinetic outcomes use different kinds of measurements from the binary DLT outcome. General statistical context: continuous concentration or exposure measures are commonly described with summaries of location and variability, while time-to-event outcomes require methods that account for event timing and censoring. The registry lists Cmax, AUC measures, Tmax, Css, R0 and CLss for 5-FU, but does not report their results or the statistical methods used to analyze them. The record’s listing of these outcomes does not establish which summaries, transformations, or models were applied.

Interpretation should also distinguish a point estimate from its uncertainty, a planning assumption from an observed result, and association from causal effect. The registry record gives selected event counts and planning assumptions but does not report a primary endpoint estimate with uncertainty or an inferential comparison between the dose groups. Those omissions limit the statistical conclusions that can be drawn.

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("Sunitinib (25 mg) in Combination With Cisplatin an", "Sunitinib (37.5 mg) in Combination With Cisplatin ")
n      <- c(24, 10)
events <- c(1, 0)
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  Sunitinib (25 mg) in Combination With Cisplatin an  24  1  4.2  0.1  21.1  0.7  20.2  1.0  20.4
ARM  Sunitinib (37.5 mg) in Combination With Cisplatin   10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including pharmacokinetic measures and objective response, in addition to the primary DLT endpoint. When analyses address multiple outcomes or repeated hypotheses, the chance of at least one apparently unusual result can increase. General statistical context: multiplicity procedures can control that risk, but the appropriate approach depends on the aims and prespecified analysis plan.

The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan. It is therefore not possible to determine whether multiple outcomes were treated as exploratory, whether any testing strategy was prespecified, or how interpretation was adjusted for the number of analyses. The listing of outcomes alone does not establish that all were formally tested.

The registry identifies the primary endpoint population as enrolled participants who received at least one dose of study drug. It does not report the number assessed for the DLT endpoint, participant-level missingness, reasons for missing outcome data, or how missing observations were handled. It also does not describe analysis populations for the secondary outcomes. These details matter because excluding participants or handling incomplete assessments differently can affect event counts and estimates.

General statistical context: a missing outcome is not automatically equivalent to no event. An analysis needs a stated rule for incomplete follow-up and a clear denominator. Since the primary DLT result and missing-data handling are not reported in the registry record, neither the completeness of endpoint ascertainment nor the sensitivity of results to missing observations can be assessed.

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: mucosal inflammation (30.0%), febrile neutropenia (20.0%), anaemia (10.0%), diarrhoea (10.0%), oesophagitis (10.0%).

The serious adverse-event entries report 7 affected participants among 24 at risk in the sunitinib 25 mg group and 5 among 10 at risk in the 37.5 mg group. For other adverse events, the corresponding entries are 24 of 24 and 10 of 10. These are counts of participants, not counts of separate event episodes. The registry’s serious-event entries should be read separately from the primary DLT endpoint.

The listed serious-event terms are mucosal inflammation (30.0%), febrile neutropenia (20.0%), anaemia (10.0%), diarrhoea (10.0%), oesophagitis (10.0%) and vomiting (10.0%). The denominator and dose-group attribution for these percentages are not reported in the registry record. The percentages should not be assumed to be within-group risks, and the terms should not be combined to estimate a total because the record does not state whether participants could contribute to more than one term.

Death counts are not reported in the registry record. These entries describe the recorded adverse events; they do not by themselves establish causation, and they cannot replace the missing DLT result.

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

The record describes an early-phase investigation of sunitinib with cisplatin and 5-fluorouracil in advanced gastric cancer. Its primary question concerns first-cycle DLTs, assessed from baseline to Day 21, among enrolled participants who received at least one dose of study drug. That focus is consistent with dose evaluation, rather than a randomized test of comparative efficacy.

The posted information identifies two sunitinib dose groups and provides adverse-event counts for those groups. It also lists serious-event terms and percentages. These data can be read as descriptive registry entries, subject to the missing denominator for the term percentages and the absence of a reported primary DLT result. They do not support an inference that one dose is safer than the other, because dose assignment was nonrandomized and the record does not report an adjusted comparison.

The record does not report the primary endpoint result, confidence intervals, statistical tests, or results for the listed objective-response and pharmacokinetic outcomes. It therefore does not establish the incidence of DLTs, the precision of an estimated DLT incidence, or a comparative treatment effect. The presence of an outcome in the registry is not evidence that a result was posted.

General statistical context: a study can be informative about feasibility and tolerability questions without being designed to estimate a comparative treatment effect. Conversely, the phase I label does not remove the need for transparent outcome reporting. To evaluate the stated dose question, readers would need the DLT definition, the count and denominator, and the analysis approach. Those details are not reported in the registry record.

The study’s results should not be extended beyond the recorded population, interventions and outcomes. In particular, the registry information does not support claims about treatment benefit or about how the combination compares with another regimen.

14. Why This Trial Matters Statistically

This trial illustrates why design and endpoint definitions are central to interpreting early-phase clinical research. The primary endpoint is a participant count for first-cycle DLTs, while the stated study purpose concerns dose tolerability. The link between that purpose and the endpoint depends on how DLTs were defined and assessed, details not reported in the registry record.

It also illustrates the difference between dose groups and randomized comparison groups. The registry lists sunitinib 25 mg and 37.5 mg groups, but describes a nonrandomized, single-group design. A numerical difference in event counts across such groups would not, by itself, establish a dose effect. Group composition and assignment processes may also matter, and the registry does not report details needed to evaluate them.

The record lists serious-event counts but does not report the primary DLT result. This makes it important to keep related safety measures distinct rather than treating all adverse events as interchangeable. Counts need clear denominators, outcome definitions and a description of how incomplete assessments are handled.

Finally, the record’s planning assumptions demonstrate that sample-size calculations depend on choices about allocation, significance level, approximation and effect size. General statistical context: such calculations are conditional on those assumptions and do not replace reporting the results actually observed. For this study, the registry record does not report the primary outcome estimate or its uncertainty, limiting what can be learned about the stated dose question from the posted information.

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.

The primary limitation for statistical interpretation is that the registry record does not report the number of participants with first-cycle DLTs, although this is the primary endpoint. Without that result, the central outcome cannot be evaluated. The record also does not report an uncertainty interval, test result or analysis method for the endpoint.

The nonrandomized design limits comparisons between the 25 mg and 37.5 mg sunitinib groups. The registry does not report how participants were assigned to those groups, whether groups differed at baseline, or whether an adjusted comparison was conducted. Any difference between their event counts would therefore be descriptive and could not be attributed to dose alone.

Important reporting details are absent. The DLT criteria, missing-data rules, participant flow through outcome assessment, and denominators for the serious-event term percentages are not reported in the registry record. Death counts are also not reported. The record lists secondary pharmacokinetic and objective-response outcomes but does not report their results or analysis methods.

The stated enrollment is 34, while adverse-event entries are presented by dose group. The registry does not explain the relationship between enrollment and the analysis populations beyond defining the primary safety population as enrolled participants who received at least one dose. The listed planning assumptions are not a substitute for a reported design justification or an outcome analysis. These limitations constrain interpretation to the design description and the specific adverse-event entries that are reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Of Sunitinib In Combination With Cisplatin And 5-Fluorouracil In Patients With Advanced Gastric Cancer — NCT00555672.
• Registry record last updated 2011-12-19; status last verified 2011-12.
• Results first posted 2011-01-05.
• 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

NCT00555672 is a completed phase I study sponsored by Pfizer. The registry describes it as nonrandomized, unmasked and single-group, with enrollment of 34 participants. It examined sunitinib malate with cisplatin and 5-fluorouracil in patients with advanced gastric cancer who had not received prior chemotherapy for their advanced cancer.

The primary outcome was the number of participants with first-cycle DLTs during Cycle 1 (Baseline to Day 21), in the safety population of enrolled participants who received at least one dose of study drug. The record lists sunitinib 25 mg and 37.5 mg groups and reports selected adverse-event counts. The primary DLT result, its statistical analysis, missing-data handling and results for the listed secondary outcomes are not reported in the registry record. The dose groups are not a randomized control comparison.