MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma (NCT00866177), a na phase 2 study. The primary outcome is Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST.

2. Clinical Question

This design addresses whether the specified tumor-response categories were observed among participants receiving AZD6244 in this study. The composite combines tumor shrinkage categories—complete and partial response—with stable disease. Those categories are distinct clinical states, so an aggregate response measure does not show how many participants fell into each category unless separate counts are reported. Such counts are not reported in the registry record.

The trial is identified as phase II and has 167 participants listed as the enrollment. That enrollment figure does not tell the reader how many participants contributed evaluable data to the primary endpoint. The endpoint population and its handling of participants with missing assessments are not reported in the registry record.

3. Trial Design

This is a completed phase II trial sponsored by the National Cancer Institute (NCI). Its registry title describes a study of AZD6244 in stage III or stage IV melanoma; the official title specifies BRAF- or NRAS-mutated melanoma. Recurrent melanoma is also listed as a condition. Enrollment is recorded as 167.

The design is single-group, with allocation listed as not applicable and masking recorded as none. Participants received the study drug rather than being assigned between a study-treatment arm and a control arm. As a result, the design can describe outcomes among participants treated in the study, but it does not provide a randomized comparison that controls for differences between treatment groups.

The arm description states that participants received oral AZD6244 twice daily on days 1-28. Courses were to repeat every 28 days in the absence of disease progression or unacceptable toxicity. The registry also lists laboratory biomarker analysis as an intervention. Further details about how that analysis related to treatment decisions or the primary endpoint are not reported in the registry record.

The registry records a start in 2009-03, primary completion in 2013-09, and status as completed. The primary endpoint is a participant count for complete response, partial response, or stable disease under RECIST, with a timeframe of up to 4 weeks. Although one outcome measure is recorded, the observed outcome value is not reported in the registry record. The number of statistical analyses is recorded as zero.

Further design details—including eligibility criteria beyond the condition and mutation descriptions, the exact assessment schedule, rules for endpoint evaluation, and the statistical analysis plan—are not reported in the registry record. These omissions limit how much can be inferred about the conduct and analysis of the trial from the registry entry alone.

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:

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.

6. Primary Endpoint

The registry lists the primary outcome as Anti-tumor Response Defined as Either a CR, PR, or SD as Defined by RECIST, measured over Up to 4 weeks.

The primary endpoint is the number of participants with an anti-tumor response defined as complete response, partial response, or stable disease under RECIST. The registry gives the unit as participants and the timeframe as up to 4 weeks. It does not report the number meeting the endpoint, the number assessed, or a proportion.

As a general statistical concept, a binary endpoint classifies each participant as meeting or not meeting a defined criterion. A count can be converted into a proportion only when the relevant denominator is known. That denominator might be all enrolled participants or a specified group with evaluable assessments; the registry record does not state which population was used for this endpoint.

As a general clinical-trial concept, a composite endpoint brings multiple component outcomes together under one definition. Here, complete response, partial response, and stable disease are grouped as a response. This can provide a broad summary, but it does not distinguish tumor response from disease stability. Component-specific results would be needed to see how much each category contributed; those results are not reported in the registry record.

RECIST is named as the response definition, but the registry entry does not provide the detailed assessment rules, the timing of individual assessments, or the endpoint's missing-assessment rules. A short stated timeframe also does not, by itself, establish how long a response lasted. Duration and later disease outcomes are not reported as part of this primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint represent?

As a general statistical concept, a binary endpoint assigns each participant to one of two categories: meeting or not meeting a prespecified criterion. For this study, the stated criterion is membership in any of three RECIST categories: complete response, partial response, or stable disease. A participant-level classification can be summarized by a count. If the denominator is known, it can also be summarized as a proportion. The registry record gives the unit as participants but does not report the endpoint count or denominator.

Binary outcomes are often analyzed with methods designed for proportions. The choice of method depends on the analysis plan, the number of observations, and the structure of the data. The statistical analysis plan for this trial is not reported in the registry record. It would therefore be inappropriate to claim that a particular model, test, or interval method was used.

Why does the composite definition matter?

As a general concept, a composite combines multiple outcomes into one endpoint. This can make a single summary easier to interpret as a broad measure of whether any qualifying outcome occurred. However, components may differ in clinical meaning and importance. Here, complete response and partial response describe response categories, while stable disease is also counted as meeting the endpoint. An aggregate count would not show which component occurred for each participant. The registry record does not report component-specific counts.

Composite endpoints also depend on consistent classification. The record refers to RECIST but does not provide the detailed rules used for assessment, confirmation, or handling of ambiguous findings. Those implementation details are not reported in the registry record. As a general principle, clear operational definitions help ensure that endpoint classification is applied consistently.

What would a confidence interval describe?

As a general statistical concept, a confidence interval expresses the uncertainty around an estimated quantity, such as a response proportion. It is not a range containing a fixed percentage of individual participant outcomes. Its width depends on the estimate and the information available, including the number of participants contributing data. Since the registry record does not report a primary endpoint estimate, denominator, or interval, precision cannot be evaluated for this endpoint.

A p-value, when used, addresses compatibility between data and a specified statistical null model; it is not a measure of effect size or clinical importance. No p-value or primary endpoint analysis is reported in the registry record. The trial's analysis plan and any hypothesis-testing framework are not reported either.

How does the single-group design shape interpretation?

As a general design principle, a single-group study can describe outcomes observed among participants receiving the study treatment. Without a concurrently assigned comparator, it does not estimate a randomized between-group contrast. Differences between observed outcomes and outcomes under another treatment cannot be isolated from other explanations using this design alone. This is why the record's allocation status and single-group model matter when interpreting a future or separately reported endpoint result.

For an endpoint assessed at a particular timeframe, the denominator and assessment rules are important. Participants who do not have an assessment may be handled in different ways under different analysis populations or missing-data procedures. The registry record does not report the analysis population, rules for missing assessments, or sensitivity analyses. No assumption about those choices should be made.

What do the planning assumptions describe?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions for an illustration, not evidence that this single-group trial was designed as a two-arm comparison. The record does not report the trial's own sample-size justification, and no sample-size calculation should be presented as the trial's observed power.

As a general concept, a planning calculation asks how much information might be needed under specified assumptions. Its result depends on the effect size, variability or event rate, allocation, significance level, and target power. Changing assumptions changes the resulting planning quantity. A planning illustration does not establish the probability that a completed study detected an effect, and it does not substitute for an observed estimate with an uncertainty interval.

The record's illustration refers to an observed effect, but the primary endpoint result needed to identify such an effect is not reported in the registry record. The illustration's numerical sample-size outputs are not restated in this explanation. They should be read only as hypothetical planning quantities under the stated assumptions, not as observed participant counts or proof of adequate power for the actual study.

What about over-dispersion?

As a general statistical concept, over-dispersion occurs when observed variability exceeds what a model assumes. It can make uncertainty estimates too small if the model does not accommodate the additional variability. For a simple binary endpoint, the relevant modeling choices and any evidence of over-dispersion would depend on the data structure and analysis method. The registry record does not report a model or an over-dispersion assessment, so no such conclusion can be made for this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry record defines one primary outcome measure, but it does not report an analysis plan, hypothesis-testing strategy, or adjustment for multiple comparisons. Multiplicity arises, as a general statistical issue, when several outcomes, time points, subgroups, or analyses are examined and results are selected for emphasis. Without a documented plan, it is not possible to determine how multiplicity was handled in this trial. No adjustment method should be inferred.

The primary outcome is a composite of complete response, partial response, and stable disease. The record does not report results for the components, subgroup analyses, or additional outcome analyses. It also records zero analyses. That registry entry does not establish whether analyses were conducted elsewhere, but it means inferential results are not reported in this record.

Missing-data handling is also not reported. The registry does not say how participants without an endpoint assessment were classified, whether any endpoint values were missing, or whether a sensitivity analysis was undertaken. The stated enrollment of 167 cannot establish the denominator used for endpoint analysis.

The analysis population is not reported in the registry record. It is therefore unknown from this entry whether the endpoint was intended to include all enrolled participants, only participants who received treatment, or a group with evaluable assessments. These populations can produce different summaries when eligibility, treatment exposure, or assessment completion varies.

As a general principle, interpretation of a clinical-trial estimate requires clarity about the population analyzed, missing outcomes, endpoint definitions, and multiplicity. Those details are not reported in the registry record, and the missing primary endpoint result prevents evaluation of the estimate regardless of which analytic choices might have been used.

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: alanine aminotransferase increased (13.3%), aspartate aminotransferase increased (13.3%), left ventricular systolic dysfunction (13.3%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, specify (13.3%), vascular disorder (13.3%).

The registry lists a safety group titled AZD6244. For serious adverse events, it reports 15 participants at risk and 6 affected. For other adverse events, it reports 15 at risk and 14 affected. These counts describe the listed safety group; the registry record does not explain how that group relates to the enrollment of 167 or why the safety denominators differ from the study enrollment.

The listed serious adverse-event terms and percentages are: Alanine aminotransferase increased, 13.3%; Aspartate aminotransferase increased, 13.3%; Left ventricular systolic dysfunction, 13.3%; Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify, 13.3%; Vascular disorder, 13.3%; and Alkaline phosphatase increased, 6.7%. Deaths are not reported in the registry record.

As a general statistical point, an affected-participant count and an event-term percentage answer different questions. A participant may experience more than one event, so event categories need not represent mutually exclusive groups. The record does not give enough detail to establish overlap among the listed terms, the duration of safety follow-up, or the criteria used to classify event severity and relatedness. The percentages should therefore be read as reported safety summaries, not as a complete account of risk or as a comparison with another treatment.

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

The record establishes that a completed phase II, single-group study of AZD6244 was registered for patients with stage III or stage IV melanoma, with the official title specifying BRAF- or NRAS-mutated melanoma. It also documents the treatment schedule and defines a primary composite endpoint based on RECIST categories. These details describe the study question and how its primary outcome was framed.

The record does not report the observed primary endpoint count, denominator, proportion, confidence interval, or inferential result. It therefore cannot support a quantitative statement about how often participants met the response definition or how precise an estimate would be. The enrollment of 167 is not a substitute for those missing endpoint data.

Even a reported composite response result would have limits. It would group complete response, partial response, and stable disease rather than describe each separately. The stated timeframe is up to 4 weeks; it does not, by itself, establish response duration or later outcomes. Such details are not reported in the registry record.

The single-group design also limits comparative interpretation. In general, outcomes in one treated group do not establish how those participants would have fared under a different treatment or without the study treatment. No randomized comparator is described, and the registry does not report a comparator-based estimate. Thus, the entry cannot establish a causal treatment effect.

The safety listing provides counts and selected serious adverse-event terms for a group titled AZD6244, but it does not report the relationship of that group to the full enrollment, detailed exposure time, or a comparative safety analysis. The figures are descriptive registry entries, not a complete characterization of safety.

Overall, the available record supports a description of the trial's design, endpoint definition, schedule, and selected safety reporting. It does not provide the primary outcome result needed to assess the magnitude or precision of the endpoint, and it does not support claims about comparative benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are not the same thing. The registry specifies a participant-level composite outcome, but does not report how many participants met it. Without the count and its denominator, there is no estimate to interpret, and without an interval there is no way to assess statistical precision from the registry entry.

It also highlights how design determines the questions that data can answer. A single-group study can describe observations in a treated group, while a randomized comparison is needed to make a direct treatment-group contrast less vulnerable to differences between groups. The record identifies no separate comparator and records allocation as not applicable. Statistical interpretation should follow that design rather than imply a comparison that was not made.

The composite outcome makes the reporting detail important. Complete response, partial response, and stable disease are grouped together, yet they are distinct categories. Reporting only an aggregate would leave readers unable to see which components contributed. The registry record does not report either the aggregate result or component-specific results.

The entry also demonstrates why enrollment should not be confused with an analysis denominator. Although enrollment is recorded as 167, the endpoint population and missing-data handling are not reported. The safety group has 15 participants at risk for serious events, a separate figure whose relationship to enrollment is not explained in the registry record.

Finally, planning assumptions should be distinguished from trial results. The record describes a hypothetical sample-size illustration with assumptions for a two-arm calculation, while the actual study is single-group. A planning illustration is not evidence of observed power or a replacement for transparent endpoint reporting. Together, these features show how design, outcome definition, denominator, and uncertainty information govern what can be concluded statistically.

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 most consequential limitation for interpreting this registry entry is that the primary endpoint result is not reported. The record identifies one outcome measure but gives no count, denominator, proportion, confidence interval, or p-value. The number of analyses is recorded as zero, so no primary endpoint analysis is available for interpretation in the registry record.

Enrollment is recorded as 167, but the endpoint analysis population is not reported. The record does not state how many participants were assessed, how many had missing assessments, or how missing outcomes were handled. Consequently, enrollment cannot be assumed to be the endpoint denominator.

The endpoint combines complete response, partial response, and stable disease. The record does not report component-specific results or detailed RECIST assessment procedures. Its timeframe is up to 4 weeks; duration of response and later outcomes are not reported as part of the stated primary endpoint.

The single-group design has no separate comparator arm, so comparative treatment effects cannot be estimated from a randomized contrast. Masking is recorded as none. The registry does not report additional design safeguards or analytic procedures that might address bias.

Safety reporting is limited to a group titled AZD6244, its at-risk and affected counts, and selected serious-event terms. The relationship between that safety group and the enrollment of 167, event overlap, exposure duration, and deaths are not reported in the registry record.

Other relevant details—including eligibility criteria, the statistical analysis plan, sample-size justification for the actual trial, handling of multiplicity, and analysis populations—are not reported in the registry record. The planning illustration's assumptions should not be mistaken for a trial-specific design justification or observed power.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: MEK Inhibitor AZD6244 in Treating Patients With Stage III or Stage IV Melanoma — NCT00866177.
• Registry record last updated 2015-08-11; status last verified 2013-06.
• Results first posted 2015-08-11.
• 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

NCT00866177 is a completed phase II, single-group trial sponsored by the National Cancer Institute (NCI), with enrollment recorded as 167. It studied oral AZD6244, listed in the interventions as Selumetinib, in stage III or stage IV melanoma; the official title specifies BRAF- or NRAS-mutated melanoma.

The treatment schedule was twice daily on days 1-28, with courses repeating every 28 days in the absence of progression or unacceptable toxicity. The primary endpoint was the participant count with complete response, partial response, or stable disease under RECIST, with a timeframe of up to 4 weeks.

The registry record does not report the primary endpoint result or a statistical analysis. It lists safety counts for an AZD6244 group and selected serious adverse-event terms. Endpoint denominator, missing-data rules, analysis population, and the trial's statistical analysis plan are not reported in the registry record.