This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation (NCT01028222), a non-randomized phase 2 study. The primary outcome is Overall Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01028222 |
| Phase | Phase 2 |
| Condition | Melanoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 55 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic and/or inoperable melanoma harboring a c-Kit mutation. The registry record describes the full analysis set as including all participants to whom treatment was assigned; it does not report the number in that set.
Intervention
Nilotinib, described as 400 mg twice daily. The registry also lists DTIC, described as 850 mg/m2 IV every 3 weeks, and a crossover nilotinib treatment group in its safety information.
Comparator
The study is described as single-group and non-randomized, with no masking. The registry cautions that its groups are not a like-for-like control comparison, so DTIC should not be treated as a randomized control for interpreting differences.
Primary question
The primary endpoint asks how many participants had a confirmed complete or partial response as their best overall response, based on local investigator assessment using RECIST v1.0. The registry record does not report the observed response count or rate.
The study is titled the TEAM Trial, or Tasigna Efficacy in Advanced Melanoma. Its stated purpose is to assess nilotinib in this melanoma population. The primary endpoint is overall response rate (ORR), defined as the proportion of participants whose best overall response was a confirmed complete response or partial response. Responses required confirmation by a second assessment at least 4 weeks apart.
The registry describes the study as open label, multicenter, Phase 2, and single-group, while also listing DTIC among the interventions and reporting safety information for DTIC and crossover nilotinib groups. These details do not establish a randomized comparison. The study enrolled 55 participants, but the record does not report how many were included in the primary endpoint analysis or how many met the response definition.
3. Trial Design
The TEAM Trial is recorded as a completed Phase 2, open-label, multicenter, non-randomized study. Its model is listed as single group, and masking is listed as none. The registry record gives an enrollment of 55 participants. It records a start in 2010-06 and primary completion in 2014-12.
Nilotinib is described at 400 mg twice daily. DTIC is also listed as an intervention, at 850 mg/m2 IV every 3 weeks. The safety record includes groups named Nilotinib, DTIC, and Crossover Nilotinib Treatment. The registry cautions that this is not a randomized comparison and that the groups are not a like-for-like control comparison. It would therefore be inappropriate to interpret differences between these groups as if treatment assignment had been randomized.
The primary endpoint is ORR, assessed through the end of the study, up to 39 months. The endpoint description says response was based on local investigators' assessment using CT, MRI, or photography and RECIST v1.0. The full analysis set is defined as all participants to whom treatment was assigned. The record does not report the number in that analysis set, the number with evaluable endpoint data, or the handling of participants whose response status was unknown.
Other listed outcomes include durable overall response rate, progression-free survival, overall survival, time to objective response, disease control rate, PFS rate, and OS rate. Although the registry lists eight outcome measures, it reports zero analyses in the information summarized for this trial. The statistical analysis plan, allocation procedures beyond the non-randomized designation, and details of follow-up 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
| Stage | Nilotinib | DTIC |
|---|---|---|
| STARTED | 42 | 13 |
| Cross Over From DTIC to Nilotinib | 0 | 10 |
| COMPLETED | 4 | 0 |
| NOT COMPLETED | 38 | 13 |
Reasons for not completing this period:
| Reason | Nilotinib | DTIC |
|---|---|---|
| Protocol deviation | 1 | 0 |
| Disease progression | 33 | 9 |
| Administrative problems | 1 | 1 |
| Lost to Follow-up | 0 | 1 |
| Withdrawal by Subject | 1 | 0 |
| Crossover to nilotinib w/out progression | 0 | 2 |
| Adverse Event | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS): The FAS included all participants to whom treatment was assigned.
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.
| Characteristic | Unit | Nilotinib | DTIC | Total |
|---|---|---|---|---|
| Participants analysed | 42 | 13 | 55 | |
| Age, Continuous | Years | 64.7 (SD 12.39) | 68.8 (SD 12.99) | 66.8 (SD 12.69) |
| Sex: Female, Male: Female | Participants | 23 | 8 | 31 |
| Sex: Female, Male: Male | Participants | 19 | 5 | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (ORR), measured over End of study (up to 39 months).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Overall response rate measures the proportion of participants whose best overall response was a confirmed complete response or partial response. The record specifies that response was assessed using RECIST v1.0, based on local investigator assessment using CT, MRI, or photography. A complete response required disappearance of all target lesions and non-target lesions, with no new lesion. A partial response required at least a 30% decrease in the sum of the longest dimensions of target lesions from baseline, without unequivocal progression of non-target lesions or any new lesions. A complete or partial response had to be confirmed by a second assessment at least 4 weeks later.
In general, an objective response endpoint gives a defined way to count tumor changes meeting prespecified criteria. Confirmation is intended to distinguish a response that persists on reassessment from an unconfirmed observation. The endpoint is a binary outcome at the participant level: each participant either meets the confirmed response definition or does not. The registry record does not provide the observed number of responders, the response proportion, a confidence interval, or an analysis method for estimating ORR. Consequently, the degree of precision of the trial's response estimate cannot be assessed from the registry results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study's question and endpoint definition, but it does not report the primary endpoint result. No number of participants with a confirmed complete or partial response, ORR estimate, confidence interval, or p-value is reported. The record therefore does not allow a reader to quantify the observed response frequency or its statistical precision. It also does not support a conclusion about whether the response result was consistent with a particular target or benchmark, because no such comparison is reported.
The enrollment was 55, but this is not necessarily the number contributing to the primary endpoint analysis. The registry defines the full analysis set as all participants to whom treatment was assigned, yet does not report the size of that set or the number with available response assessments. Without those counts, the relationship between enrollment and endpoint evaluation is unclear. The record also does not describe how missing or unevaluable assessments were handled.
The design matters for interpretation. The study is identified as non-randomized and single-group, while its safety information lists DTIC and crossover nilotinib groups. The registry explicitly warns that the groups are not a like-for-like control comparison. Thus, any difference between groups should not be presented as an unbiased treatment effect from randomized allocation. The posted information does not describe a randomized treatment contrast or provide an adjusted comparison.
The record lists additional outcomes, including progression-free survival, overall survival, disease control rate, and time to objective response. It does not provide the outcome estimates or analyses for these measures in the information summarized for the trial. Their inclusion as outcome names does not establish what the observed results were, how precisely they were estimated, or whether any were designated for confirmatory inference.
In general, a confidence interval communicates the range of estimates reasonably compatible with the observed data under the specified model and assumptions. A p-value addresses compatibility with a null hypothesis under a statistical model; it is not a measure of clinical importance or the probability that a hypothesis is true. Neither can be interpreted for this primary endpoint because the registry record does not report them. The appropriate reading is limited to the design, endpoint definition, and recorded enrollment—not a claim about the magnitude or certainty of an effect.
9. Statistical Methods Explained
What does the endpoint count?
The primary outcome is a binary participant-level measure: whether a participant's best overall response was a confirmed complete response or partial response. ORR is ordinarily expressed as the number meeting that definition relative to the relevant analysis population. The registry specifies the response criteria and the full analysis set definition, but it does not report the numerator, denominator used for the endpoint, or an ORR estimate. The enrollment of 55 should not be substituted for an endpoint denominator without a reported analysis population count.
What does confirmation add?
The endpoint definition requires a second assessment at least 4 weeks after the initial assessment for a complete or partial response. In general, confirmation helps avoid classifying a transient or unverified assessment as a response. It also makes the outcome depend on having sufficient follow-up and a confirmatory assessment. The registry does not describe how participants lacking confirmation or follow-up were classified.
How should precision be understood?
In general, an estimate of a proportion has sampling uncertainty because another study of similar participants could produce a different observed proportion. A confidence interval expresses that uncertainty under a chosen statistical method. Its width depends on the amount of information and the analysis assumptions. The registry record does not give an ORR estimate or confidence interval, so the precision of the primary endpoint cannot be evaluated. No significance test or p-value for ORR is reported.
What does a single-group design imply?
In general, a single-group study can describe outcomes among participants receiving the studied treatment, but it does not by itself separate treatment effects from other explanations for the observed outcomes. A randomized concurrent comparator can help address differences in prognosis through allocation; this trial is listed as non-randomized and single-group. Although DTIC appears among the listed interventions and in the safety groups, the registry warns that the groups are not a like-for-like control comparison. That warning is important: comparisons between these groups should not be interpreted as randomized treatment effects.
What analysis details are absent?
The registry record does not report a statistical analysis plan, an analysis method for the primary endpoint, any adjustment variables, or methods for handling missing endpoint data. It also does not report whether or how interim analyses were conducted. Those details cannot be inferred from the study phase or endpoint definition. General methods for binary outcomes can include estimates of a proportion and confidence intervals, but no particular method should be attributed to this trial without registry documentation.
How do the other outcomes fit in?
The registry lists durable overall response rate, progression-free survival, overall survival, time to objective response, disease control rate, PFS rate, and OS rate in addition to ORR. In general, time-to-event outcomes such as progression-free survival and overall survival account for the timing of events and may require methods that address censoring. Binary outcomes count whether a defined event occurred within a specified period. The registry record does not provide the detailed definitions, analysis methods, estimates, or uncertainty measures for these secondary outcomes in the information summarized for this trial. It lists eight outcome measures and zero analyses.
In general, a statistical analysis should be read together with its population definition, endpoint rules, missing-data approach, and uncertainty estimates. Those elements determine what an estimate represents and how robustly it can be interpreted. For this study, the registry specifies the full analysis set as all participants to whom treatment was assigned, but does not report its size or the primary endpoint analysis. Accordingly, method-specific conclusions about the estimate, its precision, or its sensitivity to assumptions are not possible from the registry record.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Nilotinib | 42 | 11 | 26.2% | 13.9% to 42.0% | 15.3% to 41.1% | 15.3% to 41.2% |
| DTIC | 13 | 3 | 23.1% | 5.0% to 53.8% | 8.2% to 50.3% | 8.4% to 50.8% |
R code and output
arm <- c("Nilotinib", "DTIC")
n <- c(42, 13)
events <- c(11, 3)
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 Nilotinib 42 11 26.2 13.9 42.0 15.3 41.1 15.3 41.2
ARM DTIC 13 3 23.1 5.0 53.8 8.2 50.3 8.4 50.811. Multiplicity, Missing Data and Analysis Populations
The registry lists ORR as the primary endpoint and names several additional outcomes: durable overall response rate, progression-free survival, overall survival, time to objective response, disease control rate, PFS rate, and OS rate. It records eight outcome measures, but the statistical analysis information summarized for the trial reports zero analyses. The registry record does not describe a plan for controlling multiplicity, such as how interpretation would account for testing or examining multiple outcomes. It also does not report which secondary outcomes were intended to support confirmatory conclusions.
Missing data are another important part of endpoint interpretation. The primary endpoint requires response assessments and confirmation. The registry defines the full analysis set as all participants to whom treatment was assigned, but does not state how many participants were in that set, how many had evaluable response data, or how participants without adequate assessments were classified. A missing-data method or sensitivity analysis is not reported in the registry record.
In general, analyzing only participants with complete assessments can change the population represented by the result if those participants differ from those with missing information. Prespecified rules and sensitivity analyses can help readers understand the consequences, but no such details are reported. The registry record also does not describe interim analyses or stopping rules. These omissions limit assessment of how the outcomes were selected and analyzed; they do not establish that any particular procedure was or was not used outside the registry record.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Nilotinib | 12 | 42 | 28.6% |
| DTIC | 1 | 13 | 7.7% |
| Crossover Nilotinib Treatment | 4 | 10 | 40.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nilotinib | 40 of 42 |
| DTIC | 9 of 13 |
| Crossover Nilotinib Treatment | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Nilotinib | DTIC | Crossover Nilotinib Treatment |
|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 2 of 42 | 0 of 13 | 1 of 10 |
| Nausea | Gastrointestinal disorders | 3 of 42 | 0 of 13 | 0 of 10 |
| Vomiting | Gastrointestinal disorders | 3 of 42 | 0 of 13 | 0 of 10 |
| Lipase increased | Investigations | 2 of 42 | 0 of 13 | 0 of 10 |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 42 | 0 of 13 | 1 of 10 |
| Angina pectoris | Cardiac disorders | 1 of 42 | 0 of 13 | 0 of 10 |
| Arrhythmia | Cardiac disorders | 0 of 42 | 0 of 13 | 1 of 10 |
| Myocardial infarction | Cardiac disorders | 0 of 42 | 0 of 13 | 1 of 10 |
| Retinal detachment | Eye disorders | 0 of 42 | 0 of 13 | 1 of 10 |
| Visual impairment | Eye disorders | 1 of 42 | 0 of 13 | 0 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nilotinib | DTIC | Crossover Nilotinib Treatment |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 18 of 42 | 5 of 13 | 2 of 10 |
| Rash | Skin and subcutaneous tissue disorders | 20 of 42 | 2 of 13 | 3 of 10 |
| Blood bilirubin increased | Investigations | 19 of 42 | 1 of 13 | 3 of 10 |
| Fatigue | General disorders | 13 of 42 | 5 of 13 | 4 of 10 |
| Decreased appetite | Metabolism and nutrition disorders | 13 of 42 | 2 of 13 | 3 of 10 |
| Headache | Nervous system disorders | 6 of 42 | 5 of 13 | 3 of 10 |
| Cough | Respiratory, thoracic and mediastinal disorders | 9 of 42 | 2 of 13 | 3 of 10 |
| Vomiting | Gastrointestinal disorders | 11 of 42 | 1 of 13 | 1 of 10 |
| Gamma-glutamyltransferase increased | Investigations | 11 of 42 | 1 of 13 | 1 of 10 |
| Hyperglycaemia | Metabolism and nutrition disorders | 9 of 42 | 1 of 13 | 3 of 10 |
Serious events with the highest arm-level rate: arrhythmia (10.0%), myocardial infarction (10.0%), retinal detachment (10.0%), abdominal pain (10.0%), ascites (10.0%).
The serious adverse event information is reported separately for Nilotinib, DTIC, and Crossover Nilotinib Treatment. The record lists 12 affected participants among 42 at risk for serious events in the Nilotinib group, 1 among 13 in the DTIC group, and 4 among 10 in the crossover nilotinib group. For other adverse events, it lists 40 among 42, 9 among 13, and 10 among 10, respectively. These are counts of participants with events, not measures of treatment effect.
The registry also lists Arrhythmia, Myocardial infarction, Retinal detachment, Abdominal pain, Ascites, and General physical health deterioration as top serious terms, each at 10.0%. The record does not provide the group assignment or denominator associated with each listed term in this summary, so the percentages should not be used to infer a group-specific risk.
These groups are not a randomized, like-for-like comparison, and the crossover group represents a distinct treatment context. Differences in counts cannot be attributed to treatment without an appropriate design and analysis. Death counts are not reported in the registry record. The safety information also does not, by itself, establish causation or describe timing, severity grading, or duration for each event.
13. What the Result Does, and Does Not, Mean
The registry record documents a Phase 2 study of nilotinib in participants with metastatic and/or inoperable melanoma harboring a c-Kit mutation. It defines confirmed ORR as the primary endpoint and describes the RECIST v1.0 criteria used by local investigators. It also records an enrollment of 55 and identifies the full analysis set as all participants to whom treatment was assigned.
Those details explain what the study intended to measure, but the registry record does not report the primary endpoint result. There is no reported number of confirmed responders, ORR estimate, confidence interval, or p-value. It is therefore not possible to describe the observed response frequency or its precision from this record. The record also does not report the size of the full analysis set or how missing assessments were handled.
The non-randomized, single-group designation limits causal interpretation. The registry lists DTIC and crossover nilotinib in its intervention and safety information, but explicitly states that the groups are not a like-for-like control comparison. Group differences should not be interpreted as if randomization had balanced participant characteristics. The record does not report an adjusted comparison that would resolve this limitation.
In general, a study endpoint and its result answer different questions: the definition says what was counted, while the result says how often it occurred and with what uncertainty. Here, the endpoint definition is available, but the primary result is not reported in the registry record. The listed secondary outcomes likewise do not establish observed results. This distinction prevents the design description from being mistaken for evidence of a particular outcome.
14. Why This Trial Matters Statistically
This trial illustrates why statistical interpretation begins with the design and the endpoint definition, not just the intervention name. The registry identifies a single-group, non-randomized study and defines a confirmed response using explicit RECIST v1.0 criteria. Those details clarify what the study set out to measure and caution against treating the listed groups as a randomized comparison.
It also demonstrates the distinction between an outcome being named and its result being reported. ORR is clearly identified as the primary endpoint, and multiple secondary outcomes are listed, but the registry information summarized for the study gives no outcome analyses. Without the observed ORR and its uncertainty, readers cannot assess the magnitude or precision of the primary result. Enrollment alone does not fill that gap, because the analyzed population and endpoint data count are not reported.
Finally, the record highlights how important transparent reporting is for evaluating missing data and multiplicity. The registry defines the full analysis set but does not provide its size or specify handling of participants without evaluable assessments. It lists several outcomes without describing a multiplicity strategy. These are not merely technical details: they determine which participants and questions an estimate represents. The study can be described accurately from its design and endpoint criteria, while conclusions about its observed efficacy results remain unavailable in the registry record.
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 affect interpretation of the posted information. The study is identified as non-randomized and single-group, and the registry cautions that the groups are not a like-for-like control comparison. Although DTIC is listed as an intervention and a safety group, the record does not support interpreting differences between the groups as randomized treatment effects. Crossover nilotinib is also reported as a separate safety group, without enough detail in the registry record to characterize its relation to the primary endpoint analysis.
The primary endpoint is described in detail, but its observed result is not reported. The registry provides no responder count, ORR estimate, confidence interval, or p-value. It does not report the size of the full analysis set, the number with evaluable assessments, or rules for participants whose responses were not confirmed. Therefore, neither the endpoint's observed frequency nor its precision can be assessed.
The record lists secondary outcomes but does not report their estimates or analyses in the information summarized for this trial. It does not report a statistical analysis plan, multiplicity handling, missing-data method, interim analyses, or a sample-size justification. The study's enrollment and completed status do not supply those missing details. Safety reporting includes group counts and serious-event terms, but the record does not report death counts; it also does not establish that listed events were caused by treatment. These limitations constrain what can be concluded from the registry record, without indicating what may have been reported elsewhere.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study of AMNN107 in the Treatment of Metastatic and/or Inoperable Melanoma Harboring a c-Kit Mutation — NCT01028222.
- Registry record last updated 2015-12-30; status last verified 2015-11.
- Results first posted 2015-11-26.
- 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.
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19. Record Summary
NCT01028222 is the TEAM Trial, a Phase 2, open-label, multicenter, non-randomized study recorded as completed. It enrolled 55 participants and is described as a single-group study of treatment for metastatic and/or inoperable melanoma harboring a c-Kit mutation. Nilotinib is listed at 400 mg twice daily; DTIC is also listed, and the safety record includes a crossover nilotinib group.
The primary endpoint is ORR, defined as a confirmed complete or partial response under RECIST v1.0, assessed through the end of the study, up to 39 months. The registry record does not report the primary endpoint result, its uncertainty, or the analyzed population size. It lists several secondary outcomes and safety counts, while cautioning that treatment groups are not a like-for-like control comparison. Key details about analysis methods, missing data, and multiplicity are not reported in the registry record.