SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma (NCT00577382), a na phase 2 study. The primary outcome is 2-month Progression-free Survival Rate.

2. Clinical Question

3. Trial Design

This was a completed Phase II study of sunitinib in patients with metastatic mucosal or acral/lentiginous melanoma. The registry records a start date of 2007-08, primary completion in 2014-08, and enrollment of 52. These details describe the registered study; enrollment is not necessarily the number of treated patients or the denominator used for the primary endpoint.

The design is recorded as single group, with no randomized allocation and no masking. The treatment was delivered in two cohorts with different dosing schedules. Cohort A received 50 mg of sunitinib orally each day for 4 weeks, then had a two-week treatment break. The registry says these 6-week cycles would be repeated until progression or unacceptable toxicity, up to 1 year. Cohort B received 37.5 mg daily continuously. Its full stopping criteria are not reported in the registry record.

Although there are two cohorts, they do not form a randomized comparison. A difference in outcomes between them could reflect differences in participants, treatment exposure, follow-up, or other factors, as well as any difference associated with the dosing schedules. The design does not provide the protection against confounding that random allocation can offer.

The registry lists best overall response rate, overall survival, and time to progression as secondary outcomes. It records four outcome measures and zero analyses. The protocol’s statistical plan, including any planned interim analyses or sample-size justification, is not reported in the registry record. The primary endpoint is defined as the proportion of treated patients without death or progression before 2 months, but no numerical endpoint result is reported.

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: The trial was amended in 2009 to revise sunitinib dosing due to difficulty with tolerability and evidence of progressive disease following treatment breaks. As such, there are two study cohorts: the first employing intermittent dosing of Sunitinib (Cohort A) and the second with continuous dosing (Cohort B).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of treated patients.

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.

Population: The analysis dataset is comprised of treated patients.

6. Primary Endpoint

The registry lists the primary outcome as 2-month Progression-free Survival Rate, measured over Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 2 months..

The primary endpoint, the 2-month progression-free survival rate, is a binary outcome summarized as a proportion: each patient either met the endpoint definition or did not. A patient met the definition by being alive and without documented disease progression before 2 months. The analysis population is described as treated patients.

Disease was evaluated radiologically at baseline and every 8 weeks on treatment. The endpoint definition uses RECIST 1.0 criteria. For target lesions, progressive disease was defined as at least a 20% increase in the sum of longest diameters, using the smallest sum recorded since treatment started as the reference, or the appearance of one or more new lesions. For non-target lesions, progression was defined as the appearance of one or more new lesions and/or unequivocal progression of those lesions. The endpoint timeframe also notes that treatment continued for 12 months unless progression or unacceptable toxicity occurred.

A short-term progression-free endpoint can describe whether patients have experienced death or progression by a specified point in follow-up. It does not, by itself, describe the duration of disease control beyond that point, tumor response, overall survival, or longer-term treatment effects. The registry specifies a 95% confidence interval for the rate, but the observed proportion, its interval, and its analysis denominator are not reported in the registry record. The endpoint’s clinical definition is therefore available, while its numerical estimate and precision cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods record describes a single-group Phase II study with two cohorts receiving different sunitinib schedules. There was no randomized allocation and no masking. This design can describe outcomes among treated patients, but it does not create a randomized comparison between the dosing cohorts. General statistical interpretation should therefore distinguish descriptive cohort results from estimates of causal treatment effects.

What does a binary proportion represent?

The primary endpoint is binary at the patient level: the endpoint definition is met if the patient is alive and has no RECIST-defined progression before 2 months. The reported summary would be the proportion of analyzed patients meeting that definition. To interpret such a proportion, readers need its numerator, denominator, and endpoint rules. The registry gives the endpoint rules and says the analysis dataset comprised treated patients, but the numerical result and analysis denominator are not reported in the registry record.

A binary endpoint simplifies a complex clinical course into whether a specified event or status occurred by a defined time. This makes the outcome easy to state, but it does not show when progression occurred after that time, how long patients remained progression-free, or how disease changed in other ways. The registry also lists time to progression and overall survival as secondary outcomes, which address different questions from the primary proportion.

What would the confidence interval add?

A confidence interval expresses the statistical uncertainty associated with an estimate. For a proportion, it indicates a range of values compatible with the observed data under the interval’s method and assumptions. It is not a guarantee that the true value lies within the interval, and it does not remedy limitations in study design or missing data. The registry specifies a 95% confidence interval for the primary outcome, but does not report its limits or the estimate it accompanies. The precision of the primary result therefore cannot be evaluated from the registry record.

Confidence intervals are especially useful when interpreting a result without treating a threshold for statistical significance as the whole story. An estimate can be more or less precise, and the interval helps communicate that uncertainty. Here, neither the estimate nor the interval is available in the registry record, so discussion of the result’s magnitude or precision would be speculative.

Why does the study design matter?

Random allocation helps make treatment groups comparable, on average, with respect to factors that could influence outcomes. Because this study has no randomized allocation and no like-for-like control group, any comparison between its dosing cohorts may be affected by differences in patient characteristics, clinical circumstances, follow-up, or treatment exposure. The registry does not report enough information to determine how such factors were handled. A within-study contrast between the cohorts should not be presented as a randomized treatment effect.

Masking can reduce the influence of knowledge of treatment assignment on care or outcome assessment. The registry records no masking. The primary endpoint includes radiological assessment under RECIST criteria, but the record does not report whether image assessment was centrally reviewed or conducted by assessors unaware of treatment schedule. Those details are not reported in the registry record.

What can be concluded from the listed analyses?

The registry records zero analyses, and it does not provide the primary endpoint estimate, confidence interval, or analysis denominator. It also lists secondary outcomes without numerical results in the recorded analyses. The statistical plan, including any model choices, handling of incomplete observations, and prespecified testing procedures, is not reported in the registry record. This absence limits assessment of how the endpoint was analyzed and whether the posted results correspond to a prespecified analysis.

The registry’s sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. These assumptions are not evidence that the original trial used that design or analysis. Any sample-size figures accompanying the illustrations are planning quantities, not observed power, and do not supply missing outcome evidence. The registry does not report the trial’s own sample-size justification.

In general, statistical conclusions depend on both the analysis method and the quality and completeness of the data. For a binary endpoint, the denominator and follow-up status are important, while the confidence interval reflects sampling uncertainty under the chosen method. The registry record does not provide enough outcome information to examine those features for this endpoint. It is therefore appropriate to describe the registered endpoint and design, while leaving the numerical effect and its uncertainty unresolved.

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("Cohort A-Sunitinib Intermittent Dosing", "Cohort B-Sunitinib Continuous Dosing")
n      <- c(21, 31)
events <- c(0, 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  Cohort A-Sunitinib Intermittent Dosing  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4
ARM  Cohort B-Sunitinib Continuous Dosing  31  0  0.0  0.0  11.2  0.0  11.0  0.1  10.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint as the 2-month progression-free survival rate and names best overall response rate, overall survival, and time to progression as secondary outcomes. It records four outcome measures and zero analyses. The numerical results for the primary and secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of finding an apparently notable result by chance can increase. Statistical plans may address this through a prespecified hierarchy, adjustment, or other approach. The registry record does not report whether any multiplicity procedure was planned or used. It also does not report a complete testing strategy or p-values. No claim about control of multiplicity can therefore be made.

The record defines the primary endpoint and identifies treated patients as the analysis dataset, but does not report the primary endpoint denominator or how missing assessments, loss to follow-up, or other incomplete outcome data were handled. It does not state whether missing endpoint status was counted as progression, excluded, imputed, or addressed through another method. Those decisions can affect a binary proportion, so the absence of this information limits interpretation.

The statistical analysis plan, including the handling of missing data and the definition of analysis populations beyond the treated-patient description, is not reported in the registry record. The sample-size assumptions describe planning illustrations; they are not a substitute for a trial-specific statistical plan or evidence about the analysis population. Without the missing analysis details and outcome results, the completeness and robustness of the reported endpoint cannot 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: leukocytes (9.7%), lipase (9.7%), lymphopenia (9.7%), neutrophils (9.7%), platelets (9.7%).

The registry separates serious adverse events from other adverse events for each dosing cohort. In Cohort A, 10 of 21 participants at risk were affected by a serious adverse event; 19 of 21 were affected by another adverse event. In Cohort B, 13 of 31 participants at risk were affected by a serious adverse event; 24 of 31 were affected by another adverse event. These are counts of participants recorded as affected, not counts of individual event episodes.

The registry lists Leukocytes, Lipase, Lymphopenia, Neutrophils, and Platelets at 9.7% each among the top serious terms, and Amylase at 9.5%. It does not report the cohort-specific denominators or other detail needed to interpret those term percentages fully. The listed terms should not be treated as a complete account of all serious adverse events.

These figures describe events recorded during the study; they do not establish that sunitinib caused an event. The registry record does not report deaths in the adverse-event data. It also does not provide timing, duration, severity grading, or a comparative control group for interpreting the event counts. Because the cohorts were not randomized control groups, their adverse-event counts do not support a like-for-like safety comparison between dosing schedules.

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

The record establishes that the study examined sunitinib in metastatic mucosal or acral/lentiginous melanoma and defined a short-term primary endpoint based on absence of death or RECIST-defined progression before 2 months. It also describes two dosing cohorts and records enrollment of 52. Those details clarify the clinical question and study structure.

The record does not report the observed primary endpoint rate, its 95% confidence interval, or the analysis denominator. It therefore does not show how often treated patients met the endpoint or how precisely that rate was estimated. The missing result cannot be interpreted as evidence that the outcome was common, uncommon, favorable, or unfavorable. It is a gap in the registry record, not a statistical finding.

The study’s design also limits what a comparison between cohorts could mean. The cohorts received different schedules, but treatment assignment was not randomized and there was no like-for-like control comparison. Even if cohort-specific outcomes were available, differences could not be attributed solely to the dosing schedules from this design. The registry does not report adjustments or analyses that would resolve this limitation.

The primary endpoint is distinct from best overall response rate, overall survival, and time to progression, which are listed as secondary outcomes. The registry does not report numerical analyses for those outcomes. Nor does it report the analysis plan, missing-data procedures, or multiplicity approach. Accordingly, the posted record permits description of the endpoint, treatment schedules, and some adverse-event counts, but not a quantitative assessment of efficacy, precision, or comparative treatment effects.

Sample-size planning illustrations, when shown alongside study results, should be read as hypothetical planning calculations under their stated assumptions. They are not observed power and do not fill in the absent trial result. The central statistical conclusion is limited: the question and endpoint are specified, but the registry record does not contain the primary estimate needed to answer the question numerically.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between a clearly defined clinical endpoint and a result that can be evaluated quantitatively. The endpoint specifies the status of interest, the assessment criteria, and the time point. Yet without the observed rate, confidence interval, or analysis denominator, readers cannot judge either the outcome level or its precision. A well-defined endpoint does not substitute for a reported estimate.

The trial also illustrates why study design shapes interpretation. Two treatment cohorts may appear to invite comparison, but the registry describes no randomization and explicitly cautions that they are not a like-for-like control comparison. Statistical analysis cannot automatically remove the risk that cohort differences reflect patient or follow-up differences rather than the dosing schedule.

The distinction between a proportion and a time-to-event outcome is relevant as well. The primary endpoint reduces progression-free status to a defined time point. Time to progression and overall survival are listed as secondary outcomes, but their numerical results are not reported. These outcomes answer related but nonidentical questions and cannot be substituted for the primary endpoint.

Finally, the record illustrates the value of reporting analysis details alongside endpoint definitions: denominator, missing-data handling, confidence interval, and analysis plan all affect how a result can be read. Their absence prevents a complete assessment, even though the study’s clinical question and dosing cohorts are described. Statistical transparency is therefore important not only for interpreting positive or negative estimates, but also for establishing what conclusions the available record can support.

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 most direct limitation is that the registry record does not report the primary endpoint result. The 2-month progression-free survival rate, its 95% confidence interval, and its analysis denominator are absent. The record also lists zero analyses, so the numerical result cannot be reconstructed or evaluated from the posted information.

The study has no randomized allocation and no like-for-like control group. Its two cohorts received different sunitinib schedules, but cohort membership does not create a controlled comparison. Any contrast between their outcomes would be vulnerable to differences between the groups and should not be treated as a causal estimate of one schedule versus the other.

The registry identifies treated patients as the analysis dataset but does not report how many were treated or included in the primary endpoint analysis. It does not describe missing assessments, incomplete follow-up, or the rules used to classify patients without an observed status at the endpoint. The primary endpoint relies on radiological assessment, while the record does not report details such as central review or assessor masking.

The statistical analysis plan, trial-specific sample-size justification, interim analyses, multiplicity procedures, and methods for handling missing data are not reported in the registry record. The sample-size assumptions refer to planning illustrations rather than a documented trial design analysis. These omissions restrict assessment of prespecification and analytical robustness.

Safety information is also limited. The record gives participant counts affected by serious and other adverse events and lists selected serious-event terms, but does not provide a complete event account, timing, or comparative control data. These limitations mean that the registry record supports a description of study design and selected safety counts, but not a comprehensive estimate of treatment effects or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma — NCT00577382.
• Registry record last updated 2016-12-08; status last verified 2016-06.
• Results first posted 2016-12-08.
• 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 record describes a completed Phase II, single-group study of sunitinib in metastatic mucosal or acral/lentiginous melanoma. It records enrollment of 52 and two cohorts with intermittent and continuous dosing schedules. There was no randomized allocation or masking, and the cohorts are not a like-for-like control comparison.

The primary endpoint was the 2-month progression-free survival rate among treated patients, defined by absence of death or RECIST-defined progression before 2 months. The registry specifies a 95% confidence interval but does not report the endpoint estimate, interval, or analysis denominator. It lists best overall response rate, overall survival, and time to progression as secondary outcomes, with zero analyses recorded.

The record includes adverse-event counts by cohort and selected serious-event terms. It does not report the statistical analysis plan, missing-data procedures, or trial-specific sample-size justification. The clinical question and endpoint are identifiable, but the posted results do not permit a numerical assessment of the primary outcome.