Sunitinib Malate (SUO11248) In Subjects W/ Metastatic And/Or Surgically Unresectable Hepatocellular Cancers (HCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib Malate (SUO11248) In Subjects W/ Metastatic And/Or Surgically Unresectable Hepatocellular Cancers (HCC) (NCT00495625), a na phase 2 study. The primary outcome is Number of Participants With Partial Response (PR) at Interim Analysis.

2. Clinical Question

3. Trial Design

This was a phase II, open-label, multisite, single-group study of sunitinib malate in adults with metastatic and/or surgically unresectable hepatocellular cancer. The registry lists an enrollment of 33 and a terminated status. The recorded start was 2006-10, and primary completion was 2010-12. The registry record does not report why the study was terminated.

Participants received oral, dose-escalated sunitinib malate once daily on days 1-28 of each 42-day cycle. The study summary states that treatment would continue until disease progression, cumulative or acute toxicity that the treating physician judged to compromise treatment, or the participant’s decision to stop. The registry lists one treatment group and no masking.

The primary endpoint was the number of participants with partial response at interim analysis. Its timeframe is described as on treatment to off study, with an average of 7 months per participant. The interim response population was 17 evaluable patients among the 23 enrolled by that analysis; the record gives the enrollment dates for that interim group as 10/13/06 to 9/24/07. This is a subset described at an interim analysis, not a replacement for the overall enrollment figure.

Secondary outcomes listed in the registry include time to tumor progression, overall survival, and serious adverse events. The posted record does not provide results for the first two outcomes. A single-group design can describe outcomes among treated participants, but without a separate comparison group it cannot isolate treatment effects from other explanations for those outcomes.

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: 17 of the 23 patients that were enrolled at time of Interim Analysis (patients enrolled between 10/13/06 and 9/24/07) were evaluable for response.

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 Partial Response (PR) at Interim Analysis, measured over On Treatment to Off Study - average of 7 months per participant.

The primary endpoint counts participants classified as having a partial response at interim analysis. The response definition follows RECIST: at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference. The registry says response was evaluated using the international criteria proposed by the RECIST Committee.

A response count is a binary outcome summarized as the number of participants meeting the stated criterion. It can describe how often a predefined tumor-measurement threshold was reached in the evaluated population. Such a measure is useful because it translates serial lesion measurements into a consistent category, rather than treating every small change in measurement as a response.

The endpoint is limited to the stated response definition and evaluation population. It does not, by itself, describe duration of response, time to progression, survival, or the balance of benefits and harms. Those are different questions; the registry lists some as secondary outcomes. The timeframe is on treatment to off study, with an average of 7 months per participant.

The record describes the endpoint and says that 17 of the 23 patients enrolled at interim analysis were evaluable for response, but it does not report the number who met the partial-response criterion. The response result therefore cannot be interpreted from the posted endpoint information alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the event of interest occurred. In this study, the primary event is meeting the partial-response definition at interim analysis. The natural summary is a count of participants meeting that definition. A proportion can also be useful for interpretation, but the registry record does not report the response count or a response proportion. No new response estimate can be recovered from the endpoint definition and evaluability description alone.

What does the response definition capture?

RECIST turns measurements of target lesions into a prespecified category. Here, partial response requires at least a 30% decrease in the sum of the longest diameters compared with baseline. A threshold provides a reproducible rule for classification, but it also simplifies the underlying measurements: people just below and just above a threshold may have similar measured changes while receiving different categories. The endpoint describes this specific category, not all possible changes in disease status.

The registry identifies 17 of the 23 patients enrolled at interim analysis as evaluable for response. An evaluable population is the group with information considered usable for assessing the endpoint, but the record does not define the detailed criteria used to determine evaluability. Nor does it report why the other enrolled patients were not evaluable or whether any missing measurements were imputed. Those omissions matter because the number and characteristics of people included in an analysis can affect how representative its result is of everyone enrolled.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate. For a response proportion, it would help show how precisely the study estimates the frequency of response in the analyzed population. A wider interval indicates less precision, while a narrower interval indicates greater precision under the method’s assumptions. The registry record does not report a confidence interval for the primary endpoint, and the missing response count prevents interpretation of one from the posted endpoint details.

In general, a p-value assesses how compatible observed data are with a specified statistical null model; it is not a direct measure of clinical importance or the probability that a treatment works. No primary-endpoint p-value or statistical test is reported in the registry record. The endpoint is a count in a single group, and there is no registered comparison arm against which to estimate a treatment contrast.

Why does the design matter?

The single-group, open-label design means participants and investigators were not masked to treatment, and there is no concurrent control group listed. A single-group outcome can describe what was recorded in the treated study population. It cannot, on its own, distinguish an effect of treatment from the natural course of disease, participant selection, other care, or outcome assessment. This is a design limitation, not a numerical adjustment that can be resolved by recalculating a count.

General statistical methods for counts rely on assumptions about how observations are generated. In settings where variation exceeds what a simple model expects, over-dispersion can make standard errors too small and uncertainty appear narrower than it is. That general issue may be important for some count outcomes, but the primary endpoint is defined as participants with an event, and no model or over-dispersion assessment is reported. It would be inappropriate to claim that such a method was used.

How should planning calculations be understood?

The registry’s planning assumptions describe illustrations based on an observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the planning approach is described as using total events under Schoenfeld; other planning results are expressed as participants per arm for 80% power or other stated power levels. These assumptions do not change the actual single-group design, and the planning figures are not observed power.

General sample-size calculations estimate the information needed under specified assumptions. They do not establish that a study was adequately powered after the fact, and a planning illustration is not evidence that the trial used those assumptions. The registry record does not report the trial’s sample-size justification, planned statistical analysis, interim-analysis rules, or any adjustment for multiple outcomes. With no primary response count and no reported analysis, those illustrations cannot supply a missing treatment result.

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 (SUO11248) Treatment")
n      <- c(17)
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  Sunitinib Malate (SUO11248) Treatment  17  1  5.9  0.1  28.7  1.0  27.0  1.4  27.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint and several secondary outcomes: time to tumor progression, overall survival, and serious adverse events. It does not report a multiplicity plan, such as whether the analyses were ordered, whether significance thresholds were adjusted, or which outcomes were intended to support formal statistical claims. When several outcomes are assessed, the chance of at least one apparently notable result can increase if no strategy addresses multiple testing. That is a general statistical concern; the record does not say how it was handled in this study.

The primary endpoint description identifies 17 response-evaluable patients among 23 enrolled at interim analysis. The registry does not explain why the remaining interim enrollees were not evaluable, how missing measurements were treated, or whether an intention-to-treat or other analysis population was defined. Those details are important for understanding possible selection into the response analysis. The overall enrollment is 33, but the record does not report how many of that group were included in a final primary-endpoint analysis.

Time to tumor progression and overall survival are listed as secondary outcomes, but their results and analysis populations are not reported in the registry record. No statistical analyses are listed for the outcomes. The record also does not report interim-monitoring procedures, multiplicity adjustments, or a statistical analysis plan. In the absence of those details, the endpoint listings identify questions of interest but do not establish how formal inference was conducted.

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: death - disease progression (12.1%), hemoglobin (3.0%), sudden death (3.0%), ascites - non-malignant (3.0%), dehydration (3.0%).

The serious adverse-event summary lists 11 participants affected among 33 at risk in the sunitinib malate group. The other-adverse-event summary lists 31 affected among 33 at risk. These summaries refer to different severity categories, and the record does not say whether a participant could be counted in both. They should therefore be read as separate counts, not added together.

The leading listed serious-event term is Death - Disease Progression at 12.1%. Hemoglobin, Sudden Death, Ascites - Non-malignant, Dehydration, and Diarrhea are each listed at 3.0%. The registry record does not provide event-level timing, exposure duration, relatedness assessments, or the number of unique participants associated with each listed term. A term’s reported percentage should not be interpreted as proof that treatment caused the event.

The death count is not reported in the registry record. That absence does not mean that no deaths occurred. Likewise, these adverse-event summaries do not establish a comparative safety profile because the study has no separate control group. They describe the recorded events for the treatment group within the limits of the information posted.

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

The record describes a phase II, open-label, single-group study of sunitinib malate and specifies a partial-response endpoint based on RECIST. It also identifies the population considered evaluable at interim analysis and posts adverse-event summaries. These details help clarify what the study set out to measure and which results are available in the registry.

The primary response count is not reported in the registry record. Consequently, the endpoint definition and evaluability information do not establish how many participants had a partial response, how common response was in the evaluated group, or how precisely any response frequency was estimated. Time to tumor progression and overall survival are listed as secondary outcomes, but their results are also not reported in this record.

Even if a response count were available, a single-group study would describe outcomes in the participants studied rather than provide a randomized comparison with another treatment or control. It could not by itself separate treatment effects from other explanations. The open-label design and absence of a comparator are relevant when interpreting measurements and adverse events.

The adverse-event figures describe reported affected participants and listed terms, not proof of causation. The registry does not report a death count, event timing, or enough detail to determine whether listed terms refer to unique people. The posted information therefore supports a limited descriptive account of study design and safety reporting, but does not establish a comparative treatment effect or resolve the unreported primary outcome.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and result availability constrain interpretation. A clearly defined binary endpoint can be described in plain terms: partial response required at least a 30% decrease in the summed longest diameters of target lesions relative to baseline. Yet a definition is not an outcome result. The registry identifies an interim evaluable population but does not report the number of participants meeting the response criterion.

The record also makes the distinction between enrollment populations important. Overall enrollment is 33, while the interim description concerns 23 enrolled patients, 17 of whom were evaluable for response. Without an account of evaluability rules and missing observations, readers cannot determine how the interim analysis population relates to all enrolled participants or assess possible selection effects.

The single-group design highlights another central principle: describing outcomes is different from estimating a comparative treatment effect. There is no separate control group or randomized contrast in the registry record. A count of responses or adverse events in one group cannot answer what would have happened to comparable participants under another treatment.

Finally, the record lists secondary outcomes and adverse-event categories but gives limited inferential detail. It does not report results for time to tumor progression or overall survival, or a multiplicity strategy, statistical analysis plan, or confidence intervals. These omissions illustrate why endpoint definitions, analysis populations, uncertainty estimates, and comparison structure all matter when reading clinical trial results.

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 endpoint result is not reported in the registry record. Although the endpoint is defined and the interim response-evaluable population is described, the number of partial responses is absent. This prevents a direct descriptive interpretation of the primary outcome and any assessment of its precision.

The interim population information does not explain why only 17 of the 23 enrolled patients were evaluable, what criteria determined evaluability, or how incomplete measurements were handled. The overall enrollment of 33 is not accompanied by a final primary analysis population. The registry also does not explain how the interim group relates to participants enrolled later.

The study is open-label and single group, with no separate comparator. Therefore, even a fully reported outcome would not provide a randomized comparison. The registry status is terminated, but the reason for termination is not reported in the registry record. The record does not state whether termination affected follow-up or outcome availability.

Time to tumor progression and overall survival are listed as secondary outcomes without reported results. No confidence intervals, p-values, or statistical analyses are listed. The record does not describe multiplicity handling, missing-data methods, interim-analysis procedures, or the statistical analysis plan. For safety, the death count, event timing, relatedness, and overlap between listed terms are not reported. These limitations restrict conclusions to the design features and adverse-event summaries actually posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sunitinib Malate (SUO11248) In Subjects W/ Metastatic And/Or Surgically Unresectable Hepatocellular Cancers (HCC) — NCT00495625.
• Registry record last updated 2012-03-27; status last verified 2011-12.
• Results first posted 2012-03-23.
• 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 a phase II, open-label, multisite, single-group study of oral sunitinib malate in adults with metastatic and/or surgically unresectable hepatocellular cancer. Enrollment was 33, and the study status is terminated. Treatment was dose escalated and given on days 1-28 of each 42-day cycle.

The primary endpoint was the number of participants with partial response at interim analysis, defined using RECIST as at least a 30% decrease in the sum of the longest diameters of target lesions from baseline. At interim analysis, 17 of the 23 enrolled patients were evaluable for response; the response count is not reported in the registry record.

The registry lists time to tumor progression, overall survival, and serious adverse events as secondary outcomes. It reports 11 participants with serious adverse events and 31 with other adverse events among 33 at risk. It does not report results for time to tumor progression or overall survival, a death count, or statistical analyses.