Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma (NCT00788775), a na phase 2 study. The primary outcome is 4-month Progression-Free Survival Rate.

2. Clinical Question

The study addressed a specific clinical setting: metastatic melanoma of mucosal, acral, or chronically sun-damaged types after treatment with another TKI. The registry summary describes KIT mutations in these cancers as motivation for testing a multi-targeted kinase inhibitor with KIT inhibitory activity. It also notes that patients may develop resistance to prior TKI treatment. Those statements explain the study rationale; they do not establish that a particular participant had a KIT mutation or that nilotinib altered disease outcomes.

The question is a single-group activity question rather than a comparative-effectiveness question. The primary endpoint concerns disease status at a defined time after treatment began, and the study also listed progression-free survival, overall survival, and best overall response as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. Accordingly, the record does not support a quantified estimate of the primary outcome or a comparison with an alternative treatment.

3. Trial Design

This was a phase II study sponsored by Dana-Farber Cancer Institute. The registry record lists the study as completed, with a start date of 2009-01-23 and a primary completion date of 2011-04. Enrollment was 20. Enrollment is not necessarily the same as the number included in each endpoint analysis; the primary analysis population is described as treated patients, and its exact size is not reported in the registry record.

The design was single-group, with no masking. Allocation was recorded as NA, and there was one intervention, nilotinib. Thus, there was no randomized assignment to nilotinib versus a concurrent control. The design could describe outcomes among treated participants, but it cannot by itself separate treatment-associated changes from the natural course of disease, patient selection, or other influences. A historical or external comparison is not described in the registry record.

Nilotinib was administered orally at 400 mg daily, with the daily amount described as 200 mg pills twice per day. Treatment could continue for up to 12 months while clinical benefit continued. The registry record states that disease was evaluated radiologically at baseline and every 8 weeks on treatment. Treatment could stop for disease progression or unacceptable toxicity. For the primary endpoint, the relevant status was disease status at 4 months.

The primary endpoint was the 4-month progression-free survival rate, defined as the proportion of patients absent death or progression before 4 months using RECIST criteria. The analysis dataset was comprised of treated patients. Progression-free survival, overall survival, and best overall response were listed as secondary outcomes, but their numerical results are not reported in the registry record. Detailed information about the planned statistical analysis, eligibility criteria beyond the disease and prior-TKI description, and reasons for any exclusions is 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: 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 4-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 4 months..

The primary endpoint is a proportion: the share of treated patients who met the study's definition of being free from progression and death at the 4-month assessment. The registry definition counts death or RECIST-defined progression before 4 months as an event. The registry record describes radiological disease assessment at baseline and every 8 weeks while on treatment, with disease status at 4 months relevant to this endpoint.

RECIST provides standardized rules for classifying tumor response from imaging. In the registry description, progressive disease for target lesions includes at least a 20% increase in the sum of longest diameters, using the smallest recorded sum since treatment started as the reference, or the appearance of one or more new lesions. For non-target lesions, the described progression criteria include one or more new lesions or unequivocal progression of existing non-target disease. These criteria define how a progression event is identified; they do not state how many patients experienced one.

As general statistical context, a fixed-time progression-free survival rate offers a readily interpretable snapshot of the proportion meeting an outcome definition by a chosen time. It differs from a full time-to-event summary, which uses the timing of events and can account for follow-up durations that vary across participants. The registry record names progression-free survival among the secondary outcomes but does not report the method or numerical results for that analysis.

The registry record identifies a 90% confidence interval as the measure of uncertainty for the primary endpoint, but the numerical rate and interval are not reported. Without those values, the observed proportion and the precision of its estimate cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a proportion endpoint describe?

The primary outcome is a proportion of treated patients meeting a defined condition at 4 months: no death or progression before that time. A proportion is a count-based summary. Its numerator consists of patients meeting the endpoint definition, and its denominator consists of the patients included in the analysis under the chosen rules. The registry record specifies the analysis population as treated patients, but does not report the numerical numerator, denominator, or result. It is therefore not possible to reproduce or independently assess the reported endpoint estimate from this record.

As general statistical context, proportions can be informative when the clinical question is explicitly about the share of a group meeting a condition. Their precision depends on the amount of information and on how the analysis handles participants whose outcome cannot be determined. A confidence interval expresses uncertainty around the estimated proportion; it does not guarantee that the study population represents other patients or correct for systematic bias. The registry record identifies a 90% confidence interval for the primary endpoint, but its numerical bounds are not reported.

How does RECIST contribute to the endpoint?

The registry definition uses RECIST criteria to classify progression. For target lesions, the description includes at least a 20% increase in the sum of longest diameters relative to the smallest sum recorded since treatment started, or the appearance of one or more new lesions. For non-target lesions, the description includes new lesions or unequivocal progression. Standardized rules help make imaging-based assessments more consistent by defining what qualifies as progression.

As general statistical context, applying a response criterion requires measurements, assessment timing, and rules for handling unavailable or ambiguous imaging. The registry says assessments occurred at baseline and every 8 weeks on treatment and identifies disease status at 4 months as relevant to the primary outcome. It does not report whether assessments were independently reviewed, how borderline scans were adjudicated, or how missed assessments were treated analytically. Those details are not reported in the registry record.

What does the single-group design permit?

The design is listed as single-group, with no masking and allocation recorded as NA. All participants received nilotinib as the study intervention; no concurrent randomized comparator is described. The study can therefore describe outcomes observed in its treated group, subject to the endpoint definitions and follow-up. It cannot provide a randomized estimate of the difference between nilotinib and another intervention.

As general statistical context, randomization helps balance measured and unmeasured prognostic factors between treatment groups on average. Without a randomized control group, an observed outcome cannot be cleanly separated from patient selection, prior treatment history, the course of the disease, or other care. This limitation applies even if the outcome is measured consistently. The registry record does not describe a control group or a prespecified external comparison.

How should the confidence interval be read?

The primary endpoint specifies a 90% confidence interval. As general statistical context, a confidence interval is a range of values generated by a statistical procedure to express the uncertainty associated with an estimate. Its width is influenced by the amount of information and by the method used to construct the interval. A wider interval indicates less precision under that procedure; a narrower interval indicates greater precision, but does not address bias or generalizability.

The registry record does not report the interval's endpoints or the method used to calculate it. The observed rate is also not reported, so neither the estimate nor its precision can be described numerically. No significance test for the primary endpoint is reported in the registry record.

What is the role of planning calculations?

General statistical context: sample-size planning uses assumptions about the outcome, the effect to be detected, the allocation design, and the statistical method. The registry's planning description characterizes its calculations as illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. The actual illustrated fractions and resulting sample sizes are not reported in the registry record.

Those assumptions describe a planning illustration, not the design used for this single-group study. Equal allocation between two arms does not describe the recorded trial, which has no randomized comparison. A calculation based on the observed effect is also not evidence that the study had a particular probability of detecting an effect before it was conducted. Planning numbers are hypothetical requirements under their assumptions, not observed participant counts and not observed power.

Over-dispersion is a general concern when outcome variability is greater than a simple statistical model assumes. It can make standard errors too small and confidence intervals too narrow if not accommodated. The primary endpoint is a proportion, but the registry record does not report a model or indicate whether over-dispersion adjustments were considered. It would be inappropriate to assume a particular method.

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("No CNS Metastastic Cohort", "CNS Metastatic Cohort")
n      <- c(11, 8)
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  No CNS Metastastic Cohort  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5
ARM  CNS Metastatic Cohort  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists progression-free survival, overall survival, and best overall response as secondary outcomes in addition to the 4-month progression-free survival rate. When several outcomes are examined, there can be multiple opportunities to find an apparently notable result by chance. As general statistical context, multiplicity procedures can define how inference is adjusted or prioritized across several outcomes. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or an analysis plan specifying how results across endpoints would be interpreted.

The record identifies the primary analysis population as treated patients, but does not report the exact number of treated participants, the number assessed at 4 months, or the number included in each secondary outcome analysis. The handling of missing imaging, withdrawal, loss to follow-up, or other unavailable outcome information is not reported in the registry record. Those omissions prevent assessment of whether the endpoint denominator reflects all treated patients or a subset with adequate follow-up.

The registry describes disease assessment at baseline and every 8 weeks on treatment, and treatment could continue for up to 12 months while clinical benefit continued. It does not report how assessments outside the scheduled timing were handled or how censoring was defined for any time-to-event analysis. The analysis details for progression-free survival and overall survival are not reported in the registry record.

The record contains no analysis entries and does not give a statistical analysis plan, interim-analysis approach, or missing-data strategy. These items are therefore not reported in the registry record. Their absence should not be filled in by assuming common practice. The available record supports a description of the stated endpoint and design, but not a full audit of the analysis decisions.

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: lipase (12.5%), hepatic-other (9.1%), alt, sgpt (9.1%), ast, sgot (9.1%), hyponatremia (9.1%).

The safety figures distinguish a No CNS Metastastic Cohort from a CNS Metastatic Cohort. For serious adverse events, the record lists 11 at risk and 3 affected in the no-CNS-metastatic cohort, and 8 at risk and 1 affected in the CNS-metastatic cohort. For other adverse events, it lists 11 at risk and 9 affected in the no-CNS-metastatic cohort, and 8 at risk and 6 affected in the CNS-metastatic cohort. These are the recorded counts; they are not a randomized comparison between groups.

The listed serious adverse-event terms include Lipase at 12.5%, and Hepatic-other, ALT, SGPT, AST, SGOT, Hyponatremia, and Rash/desquamation each at 9.1%. The registry record does not specify in this listing the denominator or whether a participant could contribute to more than one term. The percentages should therefore be read as the registry's reported values, not as rates recalculated from the cohort counts.

As general statistical context, adverse-event counts describe reported events or affected participants under the recording rules; they do not establish causation. The registry record does not provide event timing, severity grades beyond the serious-event classification, duration, attribution, or outcome for each term. Death counts are not reported in the registry record. These limitations restrict interpretation of the safety profile and preclude comparison with another treatment group.

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

The study's design and stated endpoint make clear what investigators sought to describe: the 4-month proportion of treated patients with metastatic mucosal, acral, or chronically sun-damaged melanoma who were alive and without RECIST-defined progression. The registry record also supplies the treatment schedule, imaging cadence, and progression criteria. However, it does not report the numerical primary endpoint result or its 90% confidence interval. The record therefore does not show the observed 4-month proportion or its precision.

The outcome definition should not be confused with a result. Stating how progression was classified does not reveal how many participants progressed, died, or remained free from these events. Similarly, the fact that the study was completed does not show whether the primary objective was met. The registry lists secondary outcomes but does not report their numerical results.

As general statistical context, an outcome observed in a single treated group is descriptive of that group and the study's assessment process. Without a randomized comparison, it cannot quantify the effect of nilotinib relative to another treatment. The design also cannot rule out influences from patient characteristics, prior treatment, or the natural course of disease. The record's rationale about KIT mutations and TKI resistance explains why nilotinib was studied, but does not establish a treatment effect or characterize the molecular features of the enrolled participants.

The enrollment count of 20 gives the scale of the study, but the treated analysis population and endpoint denominator are not reported. Neither should be inferred from enrollment. The safety figures add descriptive information about recorded adverse events in the listed cohorts, but do not establish causation or comparative risk. Taken together, the record describes a focused phase II investigation and its methods, while leaving the main numerical efficacy result and several analysis details unavailable.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way a focused clinical question is paired with a single-group design. The study targeted patients with metastatic mucosal, acral, or chronically sun-damaged melanoma following another TKI, and defined a fixed-time primary outcome using RECIST-based progression criteria. Those choices make the intended population and outcome recognizable, while the absence of a concurrent randomized comparator limits what can be inferred about treatment differences.

The primary endpoint is a proportion at 4 months, but the registry record does not report its estimate or 90% confidence interval. That absence matters because the estimate would describe the observed outcome, while its interval would indicate statistical precision under the chosen method. Without either, readers cannot assess the magnitude or uncertainty of the primary result. Enrollment was 20, but the treated analysis count and endpoint denominator are also not reported, so the information base for the estimate cannot be established from the record.

General statistical context: a small study can be useful for describing feasibility, outcome patterns, or generating hypotheses, but estimates based on limited information may be imprecise. A single-group study can document observed outcomes, yet cannot provide the same causal contrast as a randomized comparison. These are design considerations, not claims about the trial's unreported results.

The record also illustrates why outcome definitions and analytic reporting are both needed. RECIST criteria and the assessment schedule define how disease progression was to be identified. Information about missing assessments, analysis methods, and multiplicity would be needed to understand how the endpoint was calculated and how uncertainty was handled. Those details are not reported in the registry record. Thus, the trial's statistical importance lies in the clearly specified clinical setting and endpoint, alongside substantial limits on interpretation from absent numerical results and analysis detail.

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 numerical result for the primary endpoint, including its 90% confidence interval. It also does not report numerical results for the listed secondary outcomes: progression-free survival, overall survival, and best overall response. As a result, the record cannot support a quantitative description of efficacy outcomes, their precision, or consistency across endpoints.

The study had a single-group design and no concurrent randomized comparator. Any observed outcomes would therefore be descriptive of the treated participants and cannot isolate the effect of nilotinib from other influences. The registry record gives enrollment as 20, but does not report the exact treated population, endpoint denominator, or reasons for any differences between enrollment and analysis populations.

The registry describes radiological assessments at baseline and every 8 weeks on treatment, but does not report missing-data rules, handling of unevaluable scans, or details about censoring for time-to-event outcomes. It does not report the statistical analysis plan, the method used to calculate the primary confidence interval, or any multiplicity strategy. These omissions limit appraisal of how the stated outcomes were estimated.

Safety reporting is also incomplete for detailed interpretation. The record lists affected and at-risk counts by CNS-metastatic cohort and selected serious adverse-event terms, but does not report event-level timing, attribution, duration, or outcomes. Death counts are not reported in the registry record. The listed serious-event percentages have no denominator description in the record, so they should not be used to infer group-specific incidence.

Finally, the registry summary describes the clinical rationale but does not report participant-level mutation status or detailed eligibility and baseline characteristics. Such information is not reported in the registry record and cannot be assumed for the enrolled group.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma — NCT00788775.
• Registry record last updated 2018-11-15; status last verified 2018-10.
• 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

NCT00788775 is a completed phase II, single-group study sponsored by Dana-Farber Cancer Institute. The registry lists enrollment of 20, a start date of 2009-01-23, and primary completion in 2011-04. The study evaluated nilotinib in patients with metastatic mucosal, acral, or chronically sun-damaged melanoma described as resistant or intolerant to prior TKI treatment. Nilotinib was given orally at 400 mg daily, described as 200 mg pills twice per day, for up to 12 months while clinical benefit continued.

The primary endpoint was the 4-month progression-free survival rate, defined using death or RECIST-based progression before 4 months. The analysis population was treated patients, but its exact size is not reported in the registry record. Numerical results for the primary endpoint and listed secondary outcomes are not reported in the registry record. The record includes descriptive safety counts by CNS-metastatic cohort and selected serious adverse-event terms. It does not provide a concurrent randomized comparison or the analysis details needed for a complete statistical assessment.