Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization (NCT00434109), a na phase 2 study. The primary outcome is Percentage of Participants With Progression Free Survival (PFS) at 12 Months.

2. Clinical Question

In practical statistical terms, the study sought to describe the time participants remained alive without recorded disease progression after beginning the combined treatment strategy. The stated endpoint focuses on hepatic metastases for response and progression, while extrahepatic metastases were included in assessment by RECIST version 1.0. The definition of progression specifies an increase in the sum of the longest diameters of target lesions relative to the smallest recorded sum since treatment started. Because the registry record gives no primary endpoint estimate, it does not establish the observed 12-month progression-free survival rate or how precisely that rate was estimated.

3. Trial Design

This was a phase II, single-group study sponsored by H. Lee Moffitt Cancer Center and Research Institute. The registry lists enrollment as 39 and the study status as completed. Its recorded start is 2006-11, and its primary completion is 2012-02. Allocation is marked NA, and masking is listed as none. These design features mean the record describes an unmasked study without a randomized control arm.

The intervention combined sunitinib malate with selective hepatic artery embolizations. The arm description specifies a sunitinib malate dose of 37.5mg and 1-3 embolizations. Since both components appear in the same arm, this study design cannot isolate the contribution of the drug from the contribution of the embolization procedure. Nor can it estimate a treatment contrast against a concurrent group receiving a different strategy.

The primary outcome was the percentage of participants with progression-free survival at 12 months, assessed by Kaplan-Meier analysis. The registry describes additional outcomes that include overall survival at one year and at 4 years, partial radiographic response, biochemical response, and dose reduction. Those outcome labels indicate what was intended to be assessed; they do not, by themselves, supply results.

The registry record does not report the detailed eligibility criteria, treatment timing beyond the stated sequence, follow-up schedule, or complete protocol procedures. It also does not report a statistical analysis plan, a sample-size justification, or whether interim analyses were planned. The record lists 6 outcome measures and 0 analyses. The absence of posted analysis entries means that the endpoint descriptions should not be mistaken for numerical findings. In particular, the completed status and enrollment figure do not substitute for an outcome estimate or show whether the intended analysis was conducted.

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: All participants

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 Percentage of Participants With Progression Free Survival (PFS) at 12 Months, measured over 12 months.

The primary endpoint is the percentage of participants with progression-free survival at 12 months. The registry defines progression-free survival as the time from the start of treatment until disease progression or death from any cause, and specifies that the 12-month period is measured after first embolization. The endpoint is described as a Kaplan-Meier analysis among all participants, with a 95% confidence interval intended to express uncertainty around the estimate.

Time-to-event endpoints are useful when the event of interest can occur at different times and participants may have different lengths of observed follow-up. In general, Kaplan-Meier methods estimate the probability of remaining event-free over time while accounting for incomplete follow-up under their assumptions. A progression-free survival endpoint combines progression and death, so it reflects time until either event rather than time to progression alone.

The registry defines progression with a lesion-size criterion: at least a 20% increase in the sum of the longest diameters of target lesions, using the smallest recorded sum since treatment started as the reference. Response and progression endpoints refer specifically to hepatic metastases; extrahepatic metastases were included for assessment of response and progression by RECIST version 1.0. The registry record does not report the estimated 12-month percentage, the confidence interval limits, or the number of events underlying the estimate. The endpoint definition is available, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a Kaplan-Meier analysis for the primary endpoint and a 95% confidence interval as its dispersion measure. The record does not include the estimated value, confidence interval limits, analysis details, or event counts. The explanation below describes these statistical concepts generally; it does not fill in methods or results that are not reported in the registry record.

What does a Kaplan-Meier estimate describe?

In general, Kaplan-Meier analysis estimates the probability of remaining free of a specified event as time passes. For this study, the specified endpoint is progression-free survival: time from treatment start until progression or death from any cause. A participant who experiences either event has reached the endpoint. The method can use information from participants whose observation ends before an event is recorded, provided the assumptions about censoring are reasonable. The registry record does not report how censoring was handled in this analysis or how many participants were censored.

A 12-month estimate is a point on the estimated progression-free survival curve at the stated time. It is not the same as a simple count of participants known to be event-free at that time, because time-to-event methods can incorporate varying observation periods. The registry labels the outcome as a percentage of participants, but does not post the percentage itself. It is therefore not possible to describe the observed estimate from the record.

What does a confidence interval add?

In general, a confidence interval communicates statistical uncertainty around an estimate. A narrower interval indicates greater precision under the analysis assumptions; a wider interval indicates more uncertainty. A 95% confidence interval is a method-based interval with a long-run coverage interpretation under repeated use of the procedure and its assumptions. It is not a guarantee that a particular interval contains a fixed true value. Here, although the registry specifies a 95% confidence interval, it does not report its limits. The precision of the primary estimate therefore cannot be assessed.

Why does the single-group design matter?

In general, a single-group analysis estimates outcomes within the treated group. It does not, by itself, estimate what would have happened to comparable participants under a different strategy. A randomized comparison can help balance measured and unmeasured factors across groups; this registry record describes no randomized comparator. Thus, even if an outcome estimate were available, it would be a description of outcomes after the combined treatment strategy rather than a randomized estimate of its effect relative to another option.

The intervention combined sunitinib malate and hepatic artery embolizations. As a result, the design would not separate the effect of the medicine from the procedure. The record also lists masking as none. In general, lack of masking can affect assessments that involve judgment, though the record does not describe whether outcome assessment was independently masked or how imaging was reviewed.

What do the planning assumptions mean?

The registry includes assumptions for a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s own design. The study itself is listed as single-group, so an equal-allocation, two-arm illustration does not describe its observed treatment assignment. The record does not report a protocol-based sample-size justification or the numerical results of any planning illustration. Such planning quantities, when available, are not observed power and do not establish what the trial detected.

General sample-size planning asks how much information a proposed design might need to detect a specified effect under stated assumptions. The answer depends on the endpoint, event frequency, variance or other distributional features, significance threshold, power target, allocation, and analysis method. A planning result is conditional on those inputs; it is not a finding from participants in a completed study. The registry record does not report the trial’s own power target, assumptions, or justification, so none should be inferred from the planning assumptions.

How should outcome definitions be read?

The registry defines progression using a change in the sum of the longest diameters of target lesions, with the smallest recorded sum since treatment started as the reference. It specifies that hepatic metastases were the focus for response and progression, while extrahepatic metastases were included in assessment by RECIST version 1.0. In general, a stated operational definition helps readers understand what event an endpoint counts, but interpretation also depends on implementation details such as assessment timing and handling of unevaluable observations. Those details are not reported in the registry record.

Overall, the listed methods establish the intended endpoint framework but do not reveal the numerical estimate or enough implementation detail to reproduce the analysis. The endpoint definition, population label, and confidence-interval type are informative, but they do not replace a posted result and its supporting analysis details.

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 Malate and Hepatic Artery Embolizations")
n      <- c(39)
events <- c(26)
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 Malate and Hepatic Artery Embolizations  39  26  66.7  49.8  80.9  51.0  79.4  50.9  79.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary progression-free survival outcome and secondary outcomes covering overall survival at one year and at 4 years, partial radiographic response, biochemical response, and dose reduction. It records 6 outcome measures and 0 analyses. The outcome descriptions indicate areas the study intended to assess, but the record does not provide numerical findings for them.

When a study assesses multiple outcomes, multiplicity can matter because interpreting many statistical tests may increase the chance of apparently notable findings arising by chance. A prespecified hierarchy, adjustment procedure, or clearly designated primary analysis can help readers understand how results were intended to be interpreted. The record identifies a primary endpoint, but does not report a multiplicity strategy, a testing hierarchy beyond that designation, or analysis entries. It is therefore not possible to determine whether any adjustment was used or how secondary results were intended to affect conclusions.

Missing-data procedures are also not reported in the registry record. For a time-to-event endpoint, relevant details include the follow-up available, the number of participants with incomplete observation, and the rules used to censor or otherwise handle missing information. The record does not report those details, nor does it provide a flow of participants through outcome assessment.

The primary endpoint population is described as all participants. The record does not explain how this population was operationalized for the analysis, whether every enrolled participant had evaluable outcome information, or how protocol deviations and missing assessments were treated. Interim analyses, stopping rules, and a detailed statistical plan are not reported in the registry record. These omissions limit assessment of the analysis process and the completeness of outcome reporting; they do not establish that any particular procedure was or was not used.

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: hemorrhage, gi - recturm - possibly related (2.6%), nausea and vomiting - unrelated (2.6%), dysphagia - unrelated (2.6%), anorexia - unrelated (2.6%), obstruction, gi - gallbladder - unrelated (2.6%).

The registry reports serious adverse events for the arm named Sunitinib Malate and Hepatic Artery Embolizations. It records 3 affected participants among 39 at risk for serious adverse events, and 38 affected among 39 at risk for other adverse events. These are the registry’s affected-participant counts, not a description of severity grades or event duration. The deaths field is null, so deaths are not reported in the registry record.

The serious-event terms listed include gastrointestinal hemorrhage at the rectum, nausea and vomiting, dysphagia, anorexia, gallbladder obstruction, and small-bowel obstruction. Each listed term is accompanied by 2.6%. The record labels the hemorrhage as possibly related and the other listed terms as unrelated. Those labels represent the registry’s recorded relatedness assessments; the record does not give additional case details or explain how attribution was determined.

In general, adverse-event percentages and affected-participant counts describe events recorded under a study’s collection and reporting procedures. They do not establish that a treatment caused an event, and the absence of a listed event does not establish that it could not occur. Because this study has a single group and the registry gives no concurrent safety comparator, these figures should not be read as a comparative estimate of risk. The record does not report further safety-analysis details, such as event timing or severity grades.

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

The registry record describes a completed phase II investigation of sunitinib malate following hepatic artery embolization and identifies 12-month progression-free survival as the primary endpoint. It provides the endpoint definition and states that a Kaplan-Meier analysis with a 95% confidence interval was intended. However, the primary estimate and confidence interval are not reported in the registry record. The posted information therefore does not reveal the observed progression-free survival rate or its precision.

The design also shapes what any result could mean. This was a single-group study with no randomized comparator, and its intervention combined a drug and a procedure. An outcome measured in this group would describe participants receiving the combined strategy, not a randomized difference versus another treatment. It could not, on its own, distinguish the contribution of sunitinib malate from that of hepatic artery embolization or other influences on outcomes.

The record lists secondary outcomes and safety counts, but it does not post numerical findings for the efficacy outcomes. Safety entries describe affected-participant counts and selected serious-event terms, without a concurrent comparison group or detailed case information. These entries can be read as registry-recorded safety observations, not as proof that a treatment caused or prevented an event.

More broadly, an endpoint description is not an outcome finding, and a completed-study status is not evidence of a particular result. The available record is useful for understanding the intended question, treatment strategy, and outcome definitions. It does not permit conclusions about the magnitude or statistical certainty of the primary result, comparative effectiveness, or the treatment’s causal effect. The missing result information should be treated as unreported in the registry record rather than inferred from the study’s aims or design.

14. Why This Trial Matters Statistically

This study illustrates how an endpoint can be clearly defined while its statistical result remains unavailable in the registry record. The record specifies a 12-month progression-free survival measure, a Kaplan-Meier method, and a 95% confidence interval. Those details tell readers what the investigators intended to estimate, but the absent estimate and interval prevent evaluation of the observed outcome and its precision. Statistical interpretation depends on results as well as methods.

It also demonstrates why design and endpoint need to be read together. A single-group study can characterize outcomes after a treatment strategy, but it does not create a concurrent counterfactual comparison. Here, the intervention combines sunitinib malate with hepatic artery embolization. Without separate groups, the design cannot distinguish the contributions of the two components. This is a limitation of what the design can answer, not a statement about the treatment’s clinical value.

The record further highlights the difference between trial planning and trial results. The registry contains planning assumptions for an illustration, while its study design is single-group. Planning assumptions are conditional tools, not evidence of observed power or evidence that the study met a particular target. A protocol-based justification and detailed statistical plan are not reported in the registry record.

Finally, the contrast between detailed outcome labels and the absence of posted analyses is important for evidence appraisal. A complete interpretation requires estimates, uncertainty, analysis populations, and information about missing observations. When those elements are not reported, restraint is more accurate than trying to infer a result. This distinction is useful across clinical research: a defined question, a completed study, and a numerical answer are separate parts of the evidence record.

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 main limitation for interpreting this specific trial from the registry record is that it does not report the primary progression-free survival estimate or its 95% confidence interval. Although the endpoint and analysis type are specified, the numerical outcome and its precision cannot be evaluated. The record also lists 0 analyses, leaving no posted analysis results for the primary or secondary outcomes.

The single-group design provides no randomized comparator. Accordingly, the record cannot support a like-for-like treatment comparison. Because sunitinib malate and hepatic artery embolizations were administered as a combined strategy, their separate contributions cannot be identified from this design. Masking is listed as none, and the record does not describe whether outcome assessment had any additional safeguards against bias.

The registry identifies all participants as the primary population and records enrollment as 39, but does not report participant flow, outcome-specific denominators, event counts for progression-free survival, censoring details, or follow-up completeness. The timing and handling of missing outcome information are also not reported in the registry record. These gaps limit assessment of how much information supports the endpoint estimate, even if an estimate were available.

Other design and analysis details are not reported, including detailed eligibility criteria, a protocol-based sample-size justification, a full statistical analysis plan, multiplicity procedures, and interim analyses. The record does not provide enough information to assess how these matters were handled. These are limits on interpretation of the posted record; they should not be taken as proof that the study procedures themselves were inadequate or absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of Sunitinib Malate Following Hepatic Artery Embolization — NCT00434109.
• Registry record last updated 2012-09-14; status last verified 2012-07.
• Results first posted 2012-09-07.
• 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

The registry describes NCT00434109 as a completed phase II, single-group study of sunitinib malate following hepatic artery embolization for metastatic gastrointestinal neuroendocrine tumors. Enrollment is listed as 39. The intervention description specifies sunitinib malate at 37.5mg and 1-3 selective hepatic artery embolizations. Allocation is marked NA and masking is listed as none.

The primary endpoint was the percentage of participants with progression-free survival at 12 months after first embolization, analyzed by Kaplan-Meier among all participants. Progression-free survival was defined as time from treatment start to disease progression or death from any cause. The registry record does not report the primary estimate or its 95% confidence interval. It lists secondary outcomes concerning overall survival, response, and dose reduction, but does not report their numerical results. Safety entries include 3 participants affected by serious adverse events and 38 affected by other adverse events among 39 at risk; deaths are not reported in the registry record.