Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer (NCT01605916), a na phase 1 study. The primary outcome is Cmax of Selumetinib After Single Dose.

2. Clinical Question

3. Trial Design

This was a Phase I, open-label study with no masking and a single-group model. The registry lists allocation as not applicable. Enrollment is recorded as 33. The study status is completed; its recorded start was 2012-06 and its primary completion was 2015-04. AstraZeneca is listed as the sponsor.

The design covered two treatment settings. In the monotherapy setting, selumetinib was studied in cohorts at 25 mg, 50 mg, and 75 mg in Japanese patients with advanced solid malignancies. In the combination setting, selumetinib at 75 mg or 25 mg was paired with docetaxel for Japanese patients with locally advanced or metastatic non-small cell lung cancer. The official title describes the combination as second-line therapy. The listed safety cohorts include both combination cohorts and all three monotherapy cohorts.

The study objective included safety, tolerability, and pharmacokinetic assessment. The brief summary describes a combination dose-escalation phase and the possibility of a subsequent dose-expansion phase to further assess the combination. Whether that expansion occurred, and the details of any dose-escalation decisions, are not reported in the registry record.

Because treatment assignment was not randomized and the study was not designed as a like-for-like controlled comparison, the cohorts should be read as parts of a Phase I investigation rather than as treatment and control arms. The record lists 15 outcome measures and no analysis records. Details of the statistical plan, including any dose-selection criteria, 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.

Before assignment: Out of 33 enrolled subjects, 25 subjects were assigned to selumetinib (AZD6244, ARRY-142886), and 8 subjects were not assigned. The reasons of no assignment were 'Screen failure' (7 subjects) and 'Withdrawal by subject' (1 subject).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic Analysis Set

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: All subjects who received selumetinib were included into the baseline analysis population.

6. Primary Endpoint

The registry lists the primary outcome as Cmax of Selumetinib After Single Dose, measured over Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose.

The primary outcome is Cmax of selumetinib after a single oral dose. Cmax means the maximum plasma concentration reached after administration. The registry specifies that concentrations were assessed on Day 1 at 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, and 72 hours post-dose. The outcome unit is ng/mL.

Cmax is used in pharmacokinetic assessment because it describes the peak concentration observed after a dose. It can help characterize exposure and is distinct from measures of how long a drug remains in the body or the total exposure over a specified interval. The registry describes the reported parameter as a geometric mean, with geometric coefficient of variation as the dispersion measure, for the Pharmacokinetic Analysis Set.

This is a measure of drug concentration, not a direct measure of tumor shrinkage, symptom change, or survival. The registry record does not provide the numerical geometric mean, its geometric coefficient of variation, or a confidence interval for this primary outcome. Consequently, the endpoint definition and sampling schedule can be described, but the recorded information does not permit assessment of the observed Cmax level or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information is limited. The registry record identifies a Phase I open-label, single-group study, describes the primary pharmacokinetic measure, and gives safety counts by cohort. It lists 15 outcome measures but no analysis records. A detailed statistical analysis plan is not reported in the registry record. The points below explain how the named measures are generally interpreted; they do not add results to the record.

What does Cmax measure?

Cmax is the maximum plasma concentration observed after a dose. In general, pharmacokinetic studies use serial blood sampling to describe how drug concentrations change over time. The record specifies sampling from the dose time through 72 hours post-dose on Day 1. Cmax condenses that concentration-time profile to its peak value. It is not the same as total exposure: an area-under-the-curve measure summarizes exposure across a specified time interval, while Tmax identifies the time at which the peak occurs.

The primary outcome is expressed in ng/mL and summarized as a geometric mean, with geometric coefficient of variation as its dispersion measure. In general, a geometric mean is used for positive measurements that are analyzed on a multiplicative scale or have a right-skewed distribution. A geometric coefficient of variation describes relative variability on that scale. These summaries do not provide the same information as an arithmetic mean and standard deviation. The numerical summaries themselves are not reported in the registry record.

What can cohort counts tell the reader?

The safety information is displayed separately for treatment cohorts. Each entry gives the number at risk and the number affected for serious adverse events and other adverse events. These counts can describe what was recorded in each cohort. They do not establish that a treatment caused an event, and they do not make the cohorts interchangeable for statistical comparison. The study is not randomized, and the registry explicitly notes that its arms are not a like-for-like control comparison.

In general, small cohort counts produce uncertain estimates of event frequency. A count should be interpreted with its denominator and the event definition in view. A zero recorded count does not establish that an event is impossible or that the underlying risk is zero. Likewise, a reported event in a cohort does not by itself establish a causal relationship. The registry record does not give confidence intervals for the adverse-event counts or further details of event ascertainment.

How should the serious-event percentages be read?

The record lists selected serious adverse event terms with percentages. A percentage is only fully interpretable when its numerator, denominator, population, and counting method are clear. Those details are not all reported for the listed terms. The percentages can be quoted as registry entries, but they cannot support a reliable comparison between cohorts or a precise estimate of an individual event’s frequency across the study.

What does a confidence interval generally add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, nor does it by itself resolve concerns about design, measurement, or missing data. The registry record does not report confidence intervals for the primary pharmacokinetic result or for the safety counts. Thus, precision cannot be evaluated from the recorded results.

What do the planning assumptions mean?

The registry’s planning illustration is described as a calculation 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 detecting a stated fraction of the observed effect. Such planning figures are hypothetical design illustrations, not observed power and not evidence that the study was planned using those assumptions. The record does not provide the trial’s own sample-size justification, and the listed study design is not a randomized two-arm comparison. Any sample-size interpretation must therefore remain separate from the actual Phase I cohort design and its reported results.

Why does over-dispersion matter in general?

For count outcomes, over-dispersion means that observed variability exceeds what a chosen statistical model expects. If it is ignored, standard errors and uncertainty estimates can be misleading. This is a general consideration for count data, not a feature reported for this study. The registry record does not specify a model for count outcomes or describe an over-dispersion assessment.

More broadly, interpretation depends on the analysis population, missing-data handling, endpoint definitions, and statistical methods. Apart from the named Pharmacokinetic Analysis Set for the primary outcome, those details are not reported in the registry record. No adjusted analysis or inferential comparison is described in the recorded analysis information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, but no analysis records. It identifies Cmax of selumetinib after a single dose as the primary outcome and names docetaxel Cmax, Tmax, and AUC(0-12) among the secondary outcomes. The record does not describe how the other outcome measures were analyzed or whether any outcomes were designated exploratory.

Multiplicity arises when several outcomes, time points, doses, or comparisons are tested. In general, testing many hypotheses can increase the chance of at least one apparently notable result unless the analysis plan accounts for that issue. The statistical plan for multiplicity, including whether any adjustment was used, is not reported in the registry record. Because numerical endpoint results and inferential tests are not included in the recorded information, the consequences of multiplicity cannot be evaluated.

The primary outcome names a Pharmacokinetic Analysis Set, but its definition, membership, and size are not reported in the registry record. The analysis populations for the secondary outcomes and safety summaries are also not fully described. The record does not explain how missing concentration measurements, incomplete follow-up, withdrawals, or unavailable outcome data were handled. It also does not report whether any sensitivity analyses were conducted.

These omissions matter because estimates can depend on which participants and measurements are included and how missing observations are treated. The stated enrollment is not a substitute for an endpoint-specific analysis population. Without analysis-set definitions, missing-data methods, and results, the completeness and precision of the endpoint analyses cannot be assessed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: humerus fracture (25.0%), pneumonitis (16.7%), pneumonia bacterial (14.3%), interstitial lung disease (14.3%), enterocolitis (14.3%).

The safety record separates serious adverse events from other adverse events and reports counts at risk and affected within each cohort. For example, the combination cohort receiving selumetinib 75 mg with docetaxel lists 0 of 4 at risk with a serious adverse event and 4 of 4 with other adverse events. The other cohorts are likewise reported separately; these figures should not be pooled or treated as a randomized comparison.

In general, serious and other adverse events are different reporting categories. The registry does not provide additional definitions or detail about event severity, duration, recurrence, or attribution for these figures. A count of affected people also does not indicate how many events each person experienced. The record reports no death count for these cohorts; deaths are not reported in the registry record.

The listed serious-event terms and percentages are humerus fracture at 25.0%, pneumonitis at 16.7%, pneumonia bacterial at 14.3%, interstitial lung disease at 14.3%, and enterocolitis at 14.3%. Their event-specific denominators and calculation details are not reported in the registry record. These entries are descriptive, and the data do not establish causation or allow precise comparisons among treatments.

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

This study addresses pharmacokinetics and safety in a Phase I setting. Its primary outcome, selumetinib Cmax after a single dose, is a drug-concentration measure. The record specifies how that measure was defined and when samples were collected, but it does not report the numerical result. Consequently, the posted record does not establish the observed peak concentration, its variability, or the precision of its estimate.

The cohort-specific adverse-event counts describe events recorded among those listed at risk. They are not a randomized comparison, and the record does not provide enough detail to attribute events to a treatment or estimate comparative risks. The percentages attached to selected serious-event terms also lack reported denominator details. They should be interpreted as descriptive registry entries rather than definitive estimates of treatment-related harm.

The record does not report numerical results for the named docetaxel pharmacokinetic outcomes, nor does it provide a clinical efficacy outcome in the registry record described. The study therefore cannot answer from these details whether one treatment regimen improves tumor response, symptoms, or survival relative to another. It also cannot establish comparative safety between cohorts.

More broadly, a missing numerical result is not evidence of no effect or no event. It means the registry information described does not permit the estimate to be assessed. Interpretation is further limited by unreported analysis methods, analysis-set details, missing-data handling, and statistical precision. The findings should be understood as a limited registry account of a Phase I investigation, not as a complete basis for comparing treatment options.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a pharmacokinetic endpoint and a clinical outcome. Cmax measures peak plasma concentration after a dose; it does not directly measure tumor response or survival. Recognizing that distinction prevents a concentration measure from being interpreted as evidence of clinical benefit.

The study also illustrates why design labels matter. Although several dose cohorts are listed, allocation is not applicable and the model is single group. The cohorts do not constitute randomized treatment and control arms. Any numerical differences between them, if reported, would need to be interpreted in light of the non-randomized design rather than treated as an unbiased treatment contrast.

Safety counts are useful for describing what was recorded in each cohort, but their statistical meaning depends on denominators, event definitions, and uncertainty. The record lists counts and selected serious-event percentages, while leaving some denominator and analysis details unreported. Without those details and uncertainty estimates, apparent differences should not be over-read.

Finally, the record names a pharmacokinetic analysis population and several outcome measures but provides no analysis records. This highlights the importance of transparent reporting: endpoint estimates, precision, analysis populations, missing-data methods, and multiplicity decisions are needed to understand not only what was measured, but how firmly the results support a conclusion. In this record, those gaps limit interpretation more than the cohort counts alone can resolve.

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 record does not report a numerical result for the primary Cmax outcome, its geometric coefficient of variation, or a confidence interval. Although it specifies the sampling schedule and analysis population name, the membership and size of the Pharmacokinetic Analysis Set are not reported in the registry record. Numerical results for the listed docetaxel pharmacokinetic outcomes are also not reported.

The study is open-label, non-randomized, and described as single group, so its cohorts are not like-for-like controls. The record does not provide a statistical plan or a full account of dose-escalation and dose-expansion conduct. It also does not state whether the possible dose-expansion phase described in the summary took place.

For safety, the record gives cohort counts but does not provide detailed event definitions, attribution, duration, or uncertainty estimates. It lists serious-event terms with percentages but does not report the event-specific denominators or calculation details. Deaths are not reported in the registry record. The handling of missing safety or pharmacokinetic data is also not reported.

The registry lists 15 outcome measures but no analysis records. The approach to multiplicity, the statistical methods used for outcomes, and the analysis populations beyond the named primary Pharmacokinetic Analysis Set are not reported in the registry record. These limitations prevent a complete assessment of the magnitude, precision, and comparability of the study’s findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer — NCT01605916.
• Registry record last updated 2016-10-21; status last verified 2016-09.
• Results first posted 2016-07-14.
• 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

The registry record describes a completed Phase I, open-label study sponsored by AstraZeneca, with enrollment recorded as 33. It investigated selumetinib monotherapy in Japanese patients with advanced solid malignancies and selumetinib plus docetaxel in Japanese patients with locally advanced or metastatic non-small cell lung cancer. The listed selumetinib cohort doses were 25 mg, 50 mg, and 75 mg for monotherapy and 25 mg or 75 mg with docetaxel for combination therapy.

The primary outcome was selumetinib Cmax after a single dose, summarized as a geometric mean with geometric coefficient of variation in the Pharmacokinetic Analysis Set. The record also lists safety counts and docetaxel pharmacokinetic outcomes. Numerical results for the primary endpoint and the listed secondary pharmacokinetic outcomes are not reported in the registry record. No analysis records are listed, and the trial does not provide a randomized comparison.