Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma (NCT01092728), a non-randomized phase 2 study. The primary outcome is Biologic Response Evaluation of Tumors With and Without Resectable Tumors.

2. Clinical Question

The study also set out to assess safety and tolerability. For completely resectable disease, its stated secondary objectives included time to recurrence and overall survival, and whether FDG-avidity or KIT phosphorylation responses predicted those outcomes. For disease that was not completely resectable, the stated objectives included response rate, progression-free survival, and overall survival, as well as possible relationships between biological responses and those outcomes.

These objectives are questions the study intended to address, not findings. The registry record does not report results for survival, recurrence, progression, KIT phosphorylation, or an evaluable primary biological response. The registered design also does not permit a randomized treatment-effect comparison between dasatinib and another treatment or control.

3. Trial Design

This was a phase II study sponsored by M.D. Anderson Cancer Center. The registry lists the study as non-randomized, unmasked, and single-group. Enrollment is listed as 19. The study began in 2011-03, had primary completion in 2014-08, and is marked terminated. The registry record does not report why it was terminated.

The study addressed patients with acral lentiginous, mucosal, or chronic sun-damaged melanoma, separating the treatment descriptions by resectability. In the completely resectable group, the plan was dasatinib 100 mg daily for 7 days, surgical resection on Day 8, and then dasatinib 100 mg daily for a total of 12 months/12 cycles. The description defines a cycle as 4 weeks of treatment. In the unresectable group, dasatinib 100 mg daily was to continue for up to 12 months/12 cycles.

Surgical resection was listed as an intervention as well as dasatinib. This is important when reading the groups: the resectable group had a planned operation, whereas the unresectable group was described without that operation. The groups therefore reflect different clinical situations and treatment pathways. They were not randomized arms that can be treated as equivalent groups differing only in the intervention.

The primary objective focused on biological response rather than a conventional comparison of treatment against control. The registry describes a response assessment after 7 days of dasatinib, with confirmatory disease assessment no less than 4 weeks (28 days) afterward. Secondary objectives concerned safety and outcomes including recurrence, progression-free survival, and overall survival in the relevant resectability groups.

The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or a detailed account of how participants entered the groups. Those details cannot be inferred from the phase designation or the stated objectives.

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: A total of 19 participants were enrolled, out of which 18 participants were included in the analysis and 1 participant was a screen failure.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Of 4 participants in first arm, none were evaluable for response (1 inevaluable, 2 withdrawals, 1 disease progression); and of the second arm, one was inevaluable (withdrawal).

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: One participant was screen-failed prior to study group entry.

6. Primary Endpoint

The registry lists the primary outcome as Biologic Response Evaluation of Tumors With and Without Resectable Tumors, measured over Assessment at 7 Days with confirmatory disease assessment performed no less than 4 weeks (28 days) afterwards.

The primary endpoint is described as a count of participants with a biological tumor response. The registry’s response definition combines metabolic activity on positron emission tomography (PET) with a measure of tumor-cell proliferation, Ki-67. A response could be defined by at least a 25% decrease in FDG activity without a greater than 15% increase in tumoral Ki-67 expression, or by at least a 25% decrease in tumoral Ki-67 expression without a greater than 15% increase in FDG activity.

The record further defines complete metabolic response as FDG-avidity in all lesions reduced to background level. Partial metabolic response involves at least a 25% decrease in FDG-avidity, represented by change in mean SUVmax. The description says SUVmax is measured using a region of interest around each lesion corresponding to the CT image and adjusted for body weight. PET-measurable disease is defined using FDG-avidity and SUVmax criteria in the registry description.

The timing matters: the assessment was planned at 7 days, with confirmatory disease assessment no less than 4 weeks (28 days) after response criteria were first met. As a general statistical point, a prespecified biological endpoint can capture an early change in a tumor marker or imaging measure, but it does not by itself establish a durable clinical outcome. The registry record does not report evaluable primary response results, so the endpoint’s observed response count cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a participant count for a binary outcome: each participant is classified according to whether the registry’s biological-response criteria are met. As a general statistical explanation, a binary endpoint can be summarized by the number meeting the definition and the number assessed. Interpretation depends on having a clear definition, consistent assessment timing, and an analysis population that is stated transparently. The registry gives a detailed biological definition and assessment timing, but it does not report an evaluable response result.

What does a confidence interval express?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not remove limitations in the underlying data, such as missing endpoint assessments, nor does it establish that an association is causal. The registry record does not report a confidence interval for the primary endpoint.

When a binary outcome is estimated from a small group, the estimate can be imprecise. In general, the uncertainty depends on both the observed event count and the number of participants with outcome data. If few or no participants are evaluable, an endpoint estimate may be unavailable or uninformative. Here, the registry specifically reports that no participant in the completely resectable group was evaluable for response, and records an inevaluable withdrawal in the unresectable group. It does not report a response count or a response estimate for either group.

Why is randomization important for comparisons?

In general, random allocation helps make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. This supports interpretation of a difference between groups as a possible treatment effect, subject to other design and analysis assumptions. This study is registered as non-randomized and single-group. The resectable and unresectable groups also have different clinical circumstances and treatment descriptions. Their outcomes should not be interpreted as a randomized comparison of dasatinib against a control treatment.

A within-study comparison of those groups would also mix resectability status with different treatment pathways, including surgical resection in the completely resectable group. Differences between group summaries could reflect those clinical differences, selection, missingness, or other factors; the registry record does not provide an analysis that separates these explanations. General statistical caution is therefore especially important when comparing their descriptive counts.

How should missing endpoint data be considered?

In general, missing outcomes can affect both the number of participants contributing to an estimate and the interpretation of that estimate. Missingness is not automatically random: participants without an assessment may differ from those with one. Withdrawals and disease progression are distinct reasons listed for lack of evaluability in the completely resectable group, while a withdrawal is listed for the inevaluable participant in the unresectable group. The record does not state how missing responses were handled in an analysis, whether additional endpoint data were collected, or whether sensitivity analyses were performed. No particular missing-data assumption should be inferred.

The primary assessment was planned at 7 days, with confirmatory disease assessment no less than 4 weeks (28 days) after response criteria were first met. In general, a confirmation requirement can help distinguish a response that persists on reassessment from a transient reading, but it also requires the relevant follow-up assessment to be available. The posted record does not give enough information to assess completion of confirmation or the handling of participants who lacked it.

What does over-dispersion mean?

As a general concept, over-dispersion occurs when observed variability is greater than a statistical model expects. It matters for outcomes such as counts or clustered observations because a model that understates variability can make uncertainty appear smaller than it is. The primary endpoint is registered as participants with an event, a binary count, and the record does not report a fitted model or an over-dispersion assessment. It would not be appropriate to claim that over-dispersion was present or addressed in this trial.

The registry includes a planning-illustration description based on an observed effect, equal allocation between two arms, a normal approximation, and a two-sided significance level of 0.05. It describes the effect to detect as a stated fraction of the observed effect and distinguishes planning for participants per arm from total events in time-to-event calculations. These are planning assumptions, not the trial’s own design rationale and not observed power. The registry record does not report the trial’s sample-size justification, analysis plan, or interim-analysis plan. Since the endpoint response estimate is not reported, the planning illustration should not be treated as evidence about the actual treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary biological-response objective and multiple secondary objectives. Those secondary questions include safety, time to recurrence, overall survival, progression-free survival, response rate, and relationships between FDG-avidity or KIT phosphorylation responses and later outcomes. When a study examines multiple outcomes or multiple associations, general statistical practice considers the risk of chance findings across the analyses and the need to distinguish confirmatory from exploratory results.

The registry record does not report a multiplicity adjustment, a hierarchy among the secondary objectives, or a prespecified statistical analysis plan. It also lists 0 analyses. That absence of reported analyses does not establish what analyses were conducted outside the registry entry; it means the record does not present them. No adjustment method or interpretation of secondary findings should be inferred.

Missing primary response information is central to interpretation. In the completely resectable group, all 4 participants are described as not evaluable, with reasons including inevaluability, withdrawal, and disease progression. In the unresectable group, 1 participant is described as inevaluable because of withdrawal. The record does not report how these participants were handled in an endpoint analysis, whether missing outcomes were imputed, or whether sensitivity analyses were undertaken.

The registry does not give a detailed analysis population definition, such as the rules for inclusion in each endpoint analysis. It is therefore not possible to determine from this record whether the primary endpoint was analyzed in an intention-to-treat population, an evaluable population, or another defined set. These omissions limit interpretation of any endpoint estimate, and no such primary estimate is reported in the registry record.

11. 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: abdominal pain (14.3%), pleural effusion (14.3%), nausea (7.1%), pneumonia (7.1%), dehydration (7.1%).

The safety results are listed separately for dasatinib plus completely resectable disease and dasatinib plus unresectable disease. Serious adverse events were reported for 0 of 4 participants in the completely resectable group and 4 of 14 participants in the unresectable group. Other adverse events were reported for 4 of 4 and 14 of 14 participants, respectively. These are descriptive counts within the registry’s listed groups.

The serious terms most frequently listed include abdominal pain and pleural effusion, each with a reported 14.3%, and nausea, pneumonia, dehydration, and dysphagia, each with a reported 7.1%. The registry does not provide further event-level details in the available record. It also does not report a death count for these groups; the death entries are not reported in the registry record.

As a general statistical point, serious-event counts and other adverse-event counts describe different categories and should not be combined. A participant may also have more than one event, so event terms should not automatically be read as counts of unique people unless the record specifies that interpretation. Here, the term percentages’ calculation basis is not stated in the registry entries.

Because allocation was non-randomized and the groups differed in resectability and treatment pathway, these safety listings do not provide a like-for-like comparative estimate. They describe what the registry recorded, not a causal comparison of treatment-related risk.

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

The registry record documents a phase II study of dasatinib in melanoma populations defined by acral lentiginous, mucosal, or chronic sun-damaged disease, with treatment descriptions for completely resectable and unresectable disease. It specifies an early biological-response endpoint using PET FDG activity and Ki-67, alongside secondary objectives concerning safety and clinical outcomes.

What the record does not provide is an evaluable primary response estimate. The completely resectable group is reported as having no participants evaluable for response, and the unresectable group has a participant recorded as inevaluable because of withdrawal. These evaluability notes do not show whether the response definition was met by other participants; the registry record does not report the response result.

The safety entries describe serious and other adverse-event counts in the listed groups, along with selected serious-event terms and percentages. They do not establish a comparative safety effect because the groups were not randomized and differed in resectability and treatment pathway. The record also does not report results for progression-free survival, recurrence, overall survival, or the biomarker-prediction objectives.

In general, an early biological marker can help characterize a tumor’s response to treatment, but a marker response is not equivalent to evidence of longer survival or delayed recurrence. Conversely, the lack of an evaluable response result in this registry record does not establish that no biological response occurred. It means the posted record does not report an endpoint result that permits that conclusion.

The study is marked terminated, but the reason is not reported in the registry record. The record also does not provide the analysis plan, sample-size justification, or detailed missing-data methods. These limitations mean that the posted information supports a description of the study and its reported observations, but not a conclusion that dasatinib did or did not control tumors or improve clinical outcomes.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between an intended endpoint and an interpretable endpoint result. The protocol summary defines a biological-response criterion in detail, combining PET FDG activity with Ki-67 and specifying assessment and confirmation timing. Yet the registry record reports no evaluable primary response result. A precise endpoint definition is necessary for consistent measurement, but it cannot replace reporting the observed outcome and the number of participants contributing to it.

The record also illustrates why group labels matter. Completely resectable and unresectable disease correspond to different clinical settings and treatment descriptions, including surgical resection for the completely resectable group. Because the design is non-randomized, comparisons across these groups cannot isolate a treatment effect. A descriptive contrast is not the same as a randomized comparison.

Missing endpoint assessments also affect what a study can answer. The registry gives reasons why participants in the resectable group were not evaluable and records a withdrawal in the unresectable group, but does not explain the analysis handling of missing response information. In general, transparent reporting of endpoint completion, analysis populations, and missing-data methods is needed to judge how an estimate was formed and how sensitive it may be to incomplete observations.

Finally, the study objectives span biological measures, safety, recurrence, progression-free survival, and overall survival. These outcomes answer different questions and do not substitute for one another. Without reported results and a stated analysis plan, readers cannot assess the strength or precision of conclusions across those objectives. The registry entry therefore offers a case study in separating a study’s aims and definitions from the evidence actually reported.

14. 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 limitation for interpreting this trial record is that it does not report an evaluable primary biological-response result. It lists reasons for non-evaluability in the resectable group and a withdrawal in the unresectable group, but does not report a response estimate, its precision, or the handling of missing assessments.

The non-randomized, single-group design provides no randomized control comparison. The resectable and unresectable groups differ in clinical status and their listed treatment pathways, including planned surgical resection in the completely resectable group. Their descriptive outcomes cannot be interpreted as a causal treatment contrast.

The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, multiplicity approach, or defined analysis populations. It does not state how missing primary outcomes were handled or whether sensitivity analyses were performed. The planned assessment and confirmation timing is described, but completion of confirmatory assessments is not reported.

Although progression-free survival is listed as a secondary outcome, the registry record does not report results for it. Results for recurrence, overall survival, response rate, KIT phosphorylation, and the biomarker-prediction questions are also not reported. The safety summaries provide group counts and selected serious-event terms, but the available record does not provide further event-level information or the calculation basis for the term percentages. Death entries are not reported in the registry record.

The study is marked terminated, with no reason reported in the registry record. These limitations restrict interpretation to the design, endpoint definitions, evaluability information, and listed safety observations; they do not establish why the study ended or what unreported analyses may have found.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Treatment With Dasatinib in Patients With Acral Lentiginous, Mucosal, or Chronic Sun-damaged Melanoma — NCT01092728.
• Registry record last updated 2016-09-05; status last verified 2016-07.
• Results first posted 2016-09-05.
• 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.

18. Record Summary

NCT01092728 is a phase II, non-randomized, unmasked, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 19 participants with acral lentiginous, mucosal, or chronic sun-damaged melanoma and is marked terminated. The registry lists a start in 2011-03 and primary completion in 2014-08.

The primary objective concerned biological response after dasatinib, measured using PET FDG activity and tumoral Ki-67, with confirmatory assessment planned no less than 4 weeks (28 days) after response criteria were first met. Treatment descriptions differed for completely resectable and unresectable disease.

The record reports that none of the 4 participants in the completely resectable group were evaluable for response, and that 1 participant in the unresectable group was inevaluable because of withdrawal. It does not report an evaluable primary response result or results for the listed survival and biomarker objectives. Safety entries are descriptive and do not form a randomized comparison.