Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer (NCT00553696), a na phase 1 study. The primary outcome is Number of Participants With First Cycle Dose-limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a phase 1 study of sunitinib in combination with S-1 and cisplatin in participants with advanced or metastatic gastric cancer. The registry lists an enrollment of 27, a single-group model, no masking, and allocation as NA. The study status is completed. Its recorded start was 2007-11, and primary completion was 2009-07.

The study was intended to assess maximum tolerated dose and overall safety. Its primary outcome was the number of participants with first-cycle dose-limiting toxicities, assessed during Cycle 1 (Baseline to Week 4). The registry describes a DLT as any of a predefined set of unacceptable adverse events, regardless of cause. The specific list of events is not reported in the registry record.

The adverse-event listings distinguish groups by sunitinib dose and schedule, including CDD and 2/2 regimens, alongside S-1 and cisplatin. Because the study is not recorded as randomized and has no like-for-like control comparison, those listings should be read as descriptive safety information, not as estimates of comparative effects. The registry arm description is blank, and details of dose assignment or escalation are not reported in the registry record.

Secondary outcomes concern pharmacokinetics: maximum observed plasma concentration, time to maximum concentration, and area under the curve for sunitinib and its listed metabolite, tegafur and 5-FU, and total and free platinum. Numerical results for these outcomes are not reported in the registry record. The record lists 15 outcome measures but no analysis entries.

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: Three to 6 participants at each dose regimen were to be initially assessed for dose limiting toxicity (dose escalation cohort) and 10 participants were added to the maximum tolerated dose (MTD) group after MTD was determined at Sunitinib 25 mg once daily for 2 weeks followed by 2 weeks off-treatment (Schedule 2/2) regimen (MTD expansion cohort).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT Evaluation Set consisted of participants who were initially enrolled for the determination of maximam tolerated dose (MTD), and either 'experienced DLT' or 'received all of the Day 1 chemotherapy, received at least 80% of their sunitinib doses, and at least 80% of S-1 doses'.

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 Week 4).

The primary endpoint counts participants with a dose-limiting toxicity during the first treatment cycle. The registry defines the assessment window as Cycle 1 (Baseline to Week 4) and describes a DLT as any of a predefined set of unacceptable adverse events, regardless of cause. It also identifies a DLT Evaluation Set: participants initially enrolled for MTD determination who either experienced a DLT or received all Day 1 chemotherapy and at least 80% of their sunitinib and S-1 doses.

This kind of endpoint is used in early-phase dose-finding research to describe whether a regimen produces toxicities judged unacceptable during a defined initial period. In general, the count can inform decisions about dose tolerability, but it does not by itself describe the full range, timing, or duration of adverse events. Nor does the count alone establish the maximum tolerated dose; interpretation depends on the study’s dose-assignment approach and decision criteria.

The registry record does not report the number of participants with DLTs, the size of the DLT Evaluation Set, or the decision rule for selecting an MTD. It therefore does not permit an estimate of the observed DLT frequency or confirmation that an MTD was identified.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. This study is recorded as phase 1 and single-group, with allocation listed as NA and masking as none. In general, a single-group study describes outcomes among participants receiving the study regimen; without a randomized comparator, it does not estimate a treatment contrast against a control group. The safety listings across dose and schedule groups remain descriptive because the record does not identify them as randomized, exchangeable groups. Differences between such groups could reflect factors other than dose, and the registry record does not report enough design detail to assess those factors.

What does the primary count represent?

The primary measure is the number of participants with first-cycle DLTs. A count records how many participants had the event, while a rate or proportion also requires a clearly defined denominator. General statistical principle: counts are most interpretable alongside the number of participants assessed and a consistent definition of who was eligible for assessment. The registry describes a DLT Evaluation Set, but it does not report its size or the observed DLT count. No DLT rate can therefore be stated from this record.

The endpoint window is Cycle 1 (Baseline to Week 4). A fixed assessment window makes the timing of the primary safety measure explicit, but it does not summarize all adverse events over the entire study. The record describes DLTs as predefined unacceptable adverse events regardless of cause, but does not list the individual qualifying events or the adjudication process. Those details matter because a DLT count depends on both the event criteria and how participants are classified.

What can a confidence interval tell a reader?

General explanation: a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. For an event proportion, it helps show how compatible the observed data are with a range of underlying event frequencies. The registry record does not report a primary DLT estimate or a confidence interval, so the precision of that endpoint cannot be evaluated. A small or absent reported count would not, by itself, establish that the underlying risk is small; the denominator and uncertainty would also be needed.

No p-value or inferential analysis result is listed. A p-value, in general, measures how unusual the data would be under a specified statistical null model; it is not a direct measure of effect size or clinical importance. Here there is no posted primary estimate or stated comparison for which a p-value could be interpreted. The record’s listing of zero analysis entries is consistent with the absence of posted analysis results, but it does not reveal whether analyses were conducted outside the registry.

Why do dose groups not create a control comparison?

The adverse-event categories list several sunitinib dose and schedule labels, including CDD and 2/2. A dose cohort can be useful descriptively in an early-phase study, but these labels alone do not establish that participants were assigned randomly or that groups were comparable at baseline. The record explicitly identifies the study as single-group and notes that it is not a randomized comparison. Therefore, comparing counts between the listed groups would not support a causal conclusion that one dose or schedule produced more or fewer events than another.

The group labeled Sunitinib 25 mg 2/2 + S-1 + Cisplatin (All) may look like a summary category, but the registry record does not state how it relates to the other listings. It should not be assumed that all groups are mutually exclusive or that their counts can be combined. The record also does not describe the dose-escalation procedure, cohort assignment, or rules for moving between dose levels. Those elements are central to interpreting how an MTD assessment was conducted.

How should the safety percentages be read?

The record lists six serious adverse-event terms with percentages. A percentage is meaningful only with a defined denominator and method, such as whether it represents affected participants or events. Those details are not reported in the registry record. The percentages should therefore be quoted as listed and not reinterpreted as study-wide risks, dose-specific rates, or measures of comparative safety. General statistical principle: adverse-event terms may also occur in the same participant, so category counts need not represent distinct people unless the reporting method says so. The registry does not describe overlap among the listed terms.

General explanation: over-dispersion matters when count data vary more than a model’s assumed distribution allows; ignoring it can make uncertainty estimates too narrow. That issue cannot be assessed from the posted primary result because no count distribution, model, or analysis is reported. No modeling approach, adjustment strategy, or uncertainty method for the primary endpoint is reported in the registry record.

What do the pharmacokinetic outcomes add?

The named secondary outcomes include maximum observed concentration, time to maximum concentration, and area under the curve for several drugs or drug components. In general, these measures describe aspects of drug exposure: peak concentration, timing of the peak, and cumulative exposure over a specified interval. They answer different questions from the DLT count and do not substitute for the primary safety outcome. The registry names these outcomes but gives no numerical estimates, distributions, or analysis results. The relevant assay procedures, sampling schedule, treatment of values below quantification, and pharmacokinetic analysis methods are not reported in the registry record.

Overall, the statistical methods that can be identified are limited to the defined first-cycle DLT measure and the described DLT Evaluation Set. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, multiplicity adjustments, or methods for missing data. Such procedures should not be inferred from the phase or stated study objective.

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 CDD + S-1 + Cisplatin", "Sunitinib 25 mg 2/2 + S-1 + Cisplatin (Dose Escala", "Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin")
n      <- c(4, 6, 6)
events <- c(2, 1, 3)
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 CDD + S-1 + Cisplatin  4  2  50.0  6.8  93.2  15.0  85.0  14.7  85.3
ARM  Sunitinib 25 mg 2/2 + S-1 + Cisplatin (Dose Escala  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Sunitinib 37.5 mg 2/2 + S-1 + Cisplatin  6  3  50.0  11.8  88.2  18.8  81.2  18.4  81.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and 15 outcome measures, including pharmacokinetic measures. It does not report an analysis plan specifying which outcomes were tested, how outcomes were prioritized beyond the named primary endpoint, or whether any multiplicity adjustment was used. A strategy for handling multiple comparisons is not reported in the registry record.

The record describes the DLT Evaluation Set as participants initially enrolled for MTD determination who either experienced a DLT or received all Day 1 chemotherapy and at least 80% of their sunitinib and S-1 doses. It does not give the size of this set, the number excluded from it, or the primary outcome count. The full analysis populations for the secondary outcomes are not reported in the registry record.

Missing-data procedures are not reported in the registry record. In general, missing outcome information can affect interpretation if participants with incomplete assessment differ from those with complete assessment. The record does not say how incomplete first-cycle observation, missed doses, withdrawal, or unavailable pharmacokinetic samples were handled. It also does not report whether sensitivity analyses were conducted.

The registry has no analysis entries and reports no primary-outcome estimate, interval, or p-value. This means the posted record does not support assessment of multiplicity, missing-data handling, or the robustness of statistical conclusions. It does not establish whether such procedures were absent from the trial’s internal analyses.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebral infarction (100.0%), platelet count decreased (50.0%), febrile neutropenia (33.3%), gastrointestinal haemorrhage (25.0%), cholecystitis acute (25.0%).

The adverse-event listings report, by named dose and schedule group, the number at risk and the number affected by serious and other events. For the 25 mg CDD group, those counts are 4 at risk and 2 with serious events, and 4 at risk and 4 with other events. For the 25 mg 2/2 group labeled All, the counts are 16 and 8 for serious events, and 16 and 16 for other events. For the 37.5 mg 2/2 group, they are 6 and 2 for serious events, and 6 and 6 for other events. For the 12.5 mg CDD group, they are 1 and 1 for serious events, and 1 and 1 for other events.

These listings are descriptive. The registry record does not explain whether the groups overlap, define the other-event category in further detail, or provide a comparison adjusted for differences between groups. Death counts are not reported in the registry record. The serious-event terms are listed with percentages, but their denominators and calculation method are also not reported. The figures should not be treated as comparative risks or evidence that a study drug caused an event.

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

The posted information establishes that the study was designed to assess dose-limiting toxicity and overall safety when sunitinib was combined with S-1 and cisplatin in advanced or metastatic gastric cancer. It specifies a first-cycle DLT window and describes the intended DLT Evaluation Set. It also lists safety counts for several sunitinib dose and schedule groups and names pharmacokinetic outcomes.

It does not report the primary DLT count, the size of the DLT Evaluation Set, or an MTD determination. Without those results, the central dose-tolerability question cannot be answered from the registry record. The adverse-event counts and serious-event term percentages provide descriptive information, but missing denominators and analysis details limit interpretation. The lack of a randomized comparator means the listed groups do not establish comparative safety or efficacy.

The registry names pharmacokinetic outcomes but does not report their numerical results. It also does not report an efficacy outcome result. Accordingly, the record does not establish whether the regimen changed drug exposure, whether tumor outcomes differed, or whether treatment had a beneficial or harmful effect relative to another regimen.

General statistical principle: an estimate’s meaning depends on its outcome definition, analysis population, denominator, and uncertainty. In this record, several of those elements are absent for the primary outcome. The study’s completed status and stated objective should not be mistaken for a posted result. The defensible interpretation is that the registry documents the study design and some safety listings, while leaving the primary endpoint result and many supporting analytic details unreported.

14. Why This Trial Matters Statistically

This study illustrates why early-phase trial interpretation depends on more than a stated objective. The primary endpoint was a defined count of first-cycle DLTs, and the registry described which participants could enter the DLT Evaluation Set. Those details clarify what the study intended to measure. But without the observed count and the size of that set, readers cannot estimate the endpoint or assess its precision.

The record also demonstrates the distinction between dose-group descriptions and controlled comparisons. Several dose and schedule labels appear in the safety listings, yet the study is recorded as single-group and not randomized. Comparing the listed counts as if participants had been assigned to balanced treatment arms would give a misleading impression of what the design can answer. The groups describe the registry’s safety reporting; they do not provide a causal dose comparison.

More broadly, outcome definitions, denominators, analysis populations, and missing-data methods are essential components of statistical reporting. Naming pharmacokinetic outcomes is not the same as reporting their results, and listing percentages without denominators leaves uncertainty about their interpretation. The absence of a posted analysis also prevents readers from evaluating uncertainty or multiplicity handling.

The statistical lesson is not that the regimen succeeded or failed. It is that the scope of conclusions must match the information actually reported. A registry entry can describe the research question and design while leaving key results unavailable. Distinguishing documented details from unanswered analytic questions is especially important when interpreting safety and dose-finding studies.

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 principal limitation for interpretation is that the registry record does not report the primary DLT count or the size of the DLT Evaluation Set. It therefore does not permit calculation or evaluation of the primary outcome. The record also does not state whether an MTD was established, how dose decisions were made, or what dose-escalation method was used.

The arm description is blank, and details of regimen administration, participant assignment to dose and schedule groups, and changes in dose are not reported in the registry record. Although the safety listings identify several dose labels, the record does not explain whether these listings overlap or whether they represent separate cohorts. The group data cannot be treated as a randomized comparison.

The serious adverse-event percentages have no reported denominators or calculation method. The record does not provide event timing, duration, severity grading beyond the serious-event classification, attribution procedures, or details on how repeated events were counted. Death counts are not reported in the registry record.

Additional limitations include the lack of posted numerical pharmacokinetic results and analysis methods, and the absence of reported missing-data procedures, multiplicity handling, or a statistical analysis plan. The record does not give a sample-size justification or describe interim analyses. These gaps constrain interpretation of the study’s safety and pharmacokinetic findings, rather than showing that any particular analysis or procedure was or was not conducted outside the registry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Of Sunitinib With S-1 And Cisplatin For Gastric Cancer — NCT00553696.
• Registry record last updated 2015-03-13; status last verified 2015-03.
• Results first posted 2015-03-13.
• 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

NCT00553696 is a completed phase 1, single-group study of sunitinib with S-1 and cisplatin in advanced or metastatic gastric cancer. The registry lists enrollment of 27, allocation as NA, and no masking. The recorded start was 2007-11 and primary completion was 2009-07.

The primary outcome was the number of participants with first-cycle DLTs during Cycle 1 (Baseline to Week 4). The study aimed to assess MTD and overall safety. The registry record does not report the primary outcome result or whether an MTD was determined. It lists safety counts for several dose and schedule groups and names pharmacokinetic secondary outcomes, but numerical pharmacokinetic results and analysis details are not reported in the registry record.