Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery (NCT00700882), a na phase 2 study. The primary outcome is Objective Response Rate Among KIT-positive Patients.

2. Clinical Question

3. Trial Design

This is a phase II, single-group trial of dasatinib in KIT-positive patients with unresectable locally advanced or stage IV mucosal, acral and vulvovaginal melanoma. The registry record lists an enrollment of 81 and identifies the Eastern Cooperative Oncology Group as sponsor. The study is marked completed. Its recorded start date is 2009-07-02, and its primary completion date is 2016-05-06.

The study has no masking, and allocation is listed as NA. Because it is a single-group design, the primary outcome describes response among patients receiving dasatinib rather than a contrast against a concurrent control group. It cannot by itself establish how outcomes would have differed under another treatment. The record explicitly notes that the arms are not a like-for-like control comparison; the design information does not describe randomized arms.

The listed intervention is oral dasatinib at 70 mg twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. The record describes the primary outcome population as eligible and treated KIT-positive patients. It does not report the number of patients meeting that analysis definition, the number assessed for response, or the number included in an outcome calculation.

The primary outcome is objective response rate, with complete and partial responses defined using RECIST. Secondary outcomes include duration of response for dasatinib monotherapy and progression-free survival. The record lists four outcome measures, but the registry entries available do not give results for these outcomes. The protocol's statistical plan, sample-size justification, interim analyses and details of any analysis populations are not reported in the registry record.

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: eligible and treated KIT-positive 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: Eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate Among KIT-positive Patients, measured over Every 6 weeks; up to 5 years.

The primary endpoint is the proportion of eligible and treated KIT-positive patients who achieved an objective response. An objective response is a complete response or partial response under RECIST. Complete response means disappearance of all target and non-target lesions. Partial response means at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference.

A response proportion is a binary-outcome summary: each patient is classified as having or not having an objective response under the outcome definition, and the proportion describes the frequency of response in the specified population. As a general statistical concept, this type of endpoint provides a direct summary of whether tumor measurements met prespecified response criteria. It does not, by itself, describe how long a response lasted or how quickly disease progressed; duration of response and progression-free survival are listed separately as secondary outcomes.

The registry specifies assessment every 6 weeks for up to 5 years and a 90% confidence interval for the primary measure. A confidence interval conveys uncertainty around an estimated response proportion; its width depends on the amount of outcome information and the observed pattern of responses. The registry record defines the endpoint but does not report its observed estimate or interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response measure. Each eligible and treated KIT-positive patient is classified according to whether the patient had a complete or partial response under RECIST. The response proportion is the number meeting the response definition relative to the analysis population. This is a general description of how a binary proportion is interpreted; the registry record does not report the response count or denominator needed to state the trial's estimate.

What does the confidence interval represent?

The registry specifies a 90% confidence interval for the primary outcome. In general, a confidence interval expresses sampling uncertainty around an estimate. A narrower interval indicates greater precision, while a wider interval indicates less precision. Its width is affected by the amount of information in the analysis and by the estimated proportion. The interval does not describe the range of individual patient outcomes, and it does not measure the probability that the treatment is effective. Because the observed estimate and interval are not reported in the registry record, their width and implications cannot be assessed.

The confidence level is part of the statistical procedure, not a guarantee that the result is accurate or free from bias. Precision and validity are different concerns: a calculation can be precise under its assumptions while the population, outcome ascertainment or study design still limits interpretation. Here, the single-group design also means that the primary estimate would describe outcomes in the treated group without a randomized treatment contrast.

Why does the response definition matter?

RECIST supplies operational criteria for classifying response. The registry defines complete response as disappearance of all target and non-target lesions. It defines partial response as at least a 30% decrease in the sum of the longest diameters of target lesions relative to the baseline sum. These rules make the endpoint more explicit than an unstructured judgment of improvement. They also determine which observed changes count toward the response proportion. The record specifies assessment every 6 weeks for up to 5 years, but it does not report assessment completion, response adjudication procedures or the number of patients with evaluable measurements.

The response proportion is not interchangeable with duration of response or progression-free survival. A response measure classifies whether a patient met the response criteria; duration and progression-free survival address time-related outcomes. The registry lists those two outcomes as secondary measures but does not provide their outcome definitions or results in the registry record for interpretation.

What does the single-group design allow?

In general, a single-group trial can estimate outcomes observed among the group receiving the intervention. Without a concurrent control group, it does not directly estimate the difference between dasatinib and another treatment. Changes in outcomes cannot be attributed solely to the intervention from the design alone. The study is recorded as single-group, with allocation NA and no masking. No randomized comparison is described, and no like-for-like control comparison should be inferred.

The registry records enrollment of 81, but that figure does not establish the analysis denominator for the primary endpoint. The endpoint population is eligible and treated KIT-positive patients; the number satisfying that definition and the handling of patients without an evaluable assessment are not reported in the registry record. For a binary outcome, counts and the denominator are necessary to interpret both the proportion and its precision.

How should planning calculations be read?

In general, a sample-size calculation estimates how many observations a future study might need under specified assumptions. The registry's planning-illustration assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and an effect defined as a stated fraction of the observed effect. Such an illustration is not evidence about the trial's observed efficacy and is not observed power. Its assumptions do not establish the trial's own design rationale or statistical plan. The protocol's sample-size justification is not reported in the registry record.

The illustration's two-arm assumptions should also be distinguished from the registered single-group design. They describe planning conditions, not a treatment comparison conducted in this trial. No numerical planning results are stated in the registry record, and the observed primary effect needed to interpret an effect-scaled planning illustration is not reported in the registry record. No trial-specific recalculation or power conclusion can therefore be drawn from the stated assumptions alone.

More generally, over-dispersion matters when outcome variation is greater than a statistical model assumes, because standard errors and confidence intervals can then be too optimistic if the extra variation is ignored. That concept is not evidence that over-dispersion occurred in this trial. The record does not describe an over-dispersion model or any other adjustment procedure. The appropriate interpretation is therefore limited to the endpoint definition and design details actually recorded.

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("Dasatinib")
n      <- c(22)
events <- c(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  Dasatinib  22  0  0.0  0.0  15.4  -0.0  14.9  0.1  14.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including objective response rate, duration of response and progression-free survival. It does not report a multiplicity procedure, a hierarchy among outcomes, or how the primary and secondary outcomes were handled across analyses. When multiple outcomes are examined, general statistical practice may need to address the increased chance of a chance finding across tests. Without a reported plan, it is not possible to determine whether or how that issue was handled in this trial.

The record lists zero analyses. That does not provide an analysis result or demonstrate that no analyses were conducted; it means that analysis details are not available in the registry entries. The statistical analysis plan, including any interim analyses, is not reported in the registry record. No assumptions about these procedures should be made.

The primary endpoint population is described as eligible and treated KIT-positive patients. The record does not report the number in that population, whether all enrolled patients were included in the primary analysis, or whether a different analysis population was used. It also does not report how missing or unevaluable response assessments were handled, whether patients who stopped treatment were followed for outcome assessment, or how follow-up loss was addressed. These details are important because the response proportion depends on which participants and assessments contribute to its numerator and denominator.

Missingness can affect interpretation when the probability of having an observed outcome is related to a patient's outcome or clinical course. This is a general statistical concern, not a claim that a particular missing-data pattern occurred in the trial. Without the analysis population and missing-data methods, the robustness of a response estimate cannot be assessed. The registry record also does not report sensitivity analyses for missing outcomes.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: fatigue (13.3%), dyspnea (13.3%), nausea (10.7%), anemia (6.7%), pleural effusion (5.3%).

For the Dasatinib group, the registry records 75 participants at risk for serious adverse events and 35 affected. It separately records 75 at risk for other adverse events and 54 affected. The record also lists 15 deaths. These are registry-reported counts; the registry entries do not state the causes of death or establish that deaths or adverse events were caused by dasatinib.

The selected serious adverse event terms and their reported percentages are fatigue, 13.3%; dyspnea, 13.3%; nausea, 10.7%; anemia, 6.7%; pleural effusion, 5.3%; and vomiting, 4.0%. The record does not provide further details about event timing, duration, severity grading or the event-collection period in the registry record for interpretation.

As a general matter, affected-participant counts and event-term percentages are different summaries. A participant may experience more than one event term, so percentages for separate terms should not be added to create a total. The registry entries do not state whether event terms overlap or provide enough detail to interpret these entries as a comparative risk estimate. Because this is a single-group study, the safety figures are not a randomized comparison with another treatment.

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

The recorded study asks whether objective responses occurred among eligible and treated KIT-positive patients with the specified unresectable melanoma types after treatment with dasatinib. Its endpoint definition is explicit: response means complete or partial response under RECIST, with assessments every 6 weeks for up to 5 years. The design is phase II and single-group, and the registered enrollment is 81.

The registry entries do not report the observed primary response result. Without the response count, analysis denominator and confidence interval, readers cannot assess the observed response frequency or its precision from this record. The listed secondary outcomes, duration of response and progression-free survival, also have no reported results in the registry record. The definitions and estimates required to interpret those outcomes are not available in the registry record.

Even if an outcome estimate were available, a single-group study would describe outcomes in the group receiving dasatinib rather than directly compare outcomes with a concurrent control. It would not by itself establish what would have happened to comparable patients under another treatment. This is a design limitation, not a judgment about the observed outcomes.

The safety entries document reported serious and other adverse events and deaths, but the record does not establish causation or give a comparative safety estimate. The counts and selected event terms should be interpreted as descriptive observations, with the limits of the recorded follow-up and event details in mind.

Accordingly, the registry record supports a description of the clinical question, treatment regimen, design and outcome definitions. It does not support a conclusion about the magnitude or precision of the primary result, a treatment-versus-control effect, or the causes of the recorded safety events. Those distinctions separate what the registered study set out to measure from what its available result record allows readers to conclude.

14. Why This Trial Matters Statistically

This trial is statistically notable for the relationship between its narrowly defined outcome population and its single-group design. The primary response measure is specified for eligible and treated KIT-positive patients, while the recorded enrollment is 81. The registry does not report how many patients met the endpoint population definition or contributed evaluable response information. This makes the missing denominator especially important: enrollment alone is not enough to interpret a response proportion.

The objective response endpoint is defined using RECIST, with complete and partial response criteria stated in the record. Explicit criteria help make the outcome reproducible and distinguish response classification from less structured assessments. The record also specifies the assessment schedule and a 90% confidence interval, indicating that uncertainty around the proportion is part of the planned endpoint description. However, without the actual estimate and interval, the intended statistical summary cannot be evaluated.

The study's single-group structure is central to interpretation. It can describe outcomes in the treated cohort, but it does not yield a randomized comparison with a concurrent control. That distinction remains important even when a response measure is clinically direct. The design supports a different type of inference from a controlled comparison, and the registry record explicitly cautions that arms are not a like-for-like control comparison.

Finally, the record separates a primary binary response outcome from secondary time-to-event outcomes and lists safety observations. Those outcomes address distinct questions and require their own denominators, definitions and analysis details. The fact that the registry identifies them does not mean their results or statistical handling are reported. This trial therefore illustrates why statistical interpretation depends not only on the endpoint label, but also on the analysis population, observed result, uncertainty estimate and design that generated the data.

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.

Several trial-specific limitations follow from the available registry record. Most importantly, it defines the primary response endpoint but does not report its observed count, proportion or 90% confidence interval. The primary analysis denominator is also not reported, even though the endpoint is restricted to eligible and treated KIT-positive patients. The recorded enrollment of 81 cannot substitute for that denominator.

The design is single-group, with no masking and allocation listed as NA. No concurrent randomized comparator is described, so the study does not provide a like-for-like control comparison. Any interpretation of outcomes as a treatment effect would exceed what this design alone can establish.

The record lists duration of response and progression-free survival as secondary outcomes but does not give their results or, in the registry record, their operational definitions. It lists four outcome measures and zero analyses, but the statistical analysis plan, multiplicity handling, interim analyses and sample-size justification are not reported in the registry record.

Missing-data handling and the analysis populations are also not reported. The registry entries do not say how unevaluable assessments, loss to follow-up or treatment discontinuation were handled for the primary endpoint. This prevents assessment of how the outcome population was formed and whether the response estimate might be sensitive to missing observations.

For safety, the record provides affected counts, a death count and selected serious event terms, but does not state event timing, collection period, causes of death or causal attribution. The single-group design also prevents a randomized comparative safety interpretation. These gaps constrain interpretation of both efficacy and safety; they do not establish that any particular bias, missingness pattern or adverse-event cause occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery — NCT00700882.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2020-02-24.
• 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 record describes a completed phase II, single-group trial of oral dasatinib for KIT-positive patients with unresectable locally advanced or stage IV mucosal, acral and vulvovaginal melanoma. Enrollment is listed as 81. The intervention regimen was 70 mg twice daily on days 1-21, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity.

The primary outcome was objective response among eligible and treated KIT-positive patients, defined as complete or partial response under RECIST and assessed every 6 weeks for up to 5 years. The registry specifies a 90% confidence interval but does not report the observed primary result. Duration of response and progression-free survival are listed as secondary outcomes without results in the registry record.

The safety record includes serious and other adverse-event counts, selected serious event terms and deaths. The design does not support a randomized treatment comparison, and the registry does not report the analysis population, missing-data methods, statistical plan or sample-size justification.