MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery (NCT01425879), a na phase 2 study. The primary outcome is Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1.

2. Clinical Question

This is a phase II investigation of a drug in a selected, difficult-to-treat cancer population. Its single-group structure can describe what happened during treatment, including measured tumor responses and adverse events, but it cannot by itself separate a treatment effect from other explanations for observed outcomes. Patient selection, the natural course of disease, assessment practices, and the timing of evaluation may all affect outcomes in an uncontrolled study.

The trial title and summary refer to advanced refractory biliary cancer that cannot be removed by surgery. The condition list is broader in its wording, including liver, gallbladder, and bile duct cancers. The registry record does not give further detail about how eligibility criteria defined the exact disease groups enrolled, or how many participants had each condition. Generalization to any particular subtype should therefore be cautious.

3. Trial Design

This was a phase II, single-group study sponsored by the National Cancer Institute (NCI). The record identifies the allocation as not applicable and masking as none. There was no randomized control arm, and the study is not a like-for-like comparison between groups. The listed enrollment was 8. The study began in 2011-04, reached primary completion in 2013-05, and is marked completed.

Participants received Akt inhibitor MK-2206 by mouth on days 1, 8, 15, and 22. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. Diagnostic laboratory biomarker analysis and a pharmacological study were also listed as interventions, but the registry record does not describe their procedures or how their results were incorporated into the primary analysis.

The primary outcome was overall response rate, defined as complete response plus partial response under RECIST 1.1. Response was assessed by MRI for target lesions. The outcome timeframe was up to 4 weeks after completion of study treatment, with total treatment time of up to 1 year. The record also lists frequency of adverse events related to MK-2206, overall survival, and progression-free survival as secondary outcomes.

Important operational details are not reported in the registry record. These include the eligibility criteria in full, the analysis population, the timing and schedule of all assessments, the statistical plan, and how participants who stopped treatment early were handled. The record also does not report whether response assessment was independently reviewed or how missing assessments affected endpoint classification. Those omissions limit evaluation of how consistently outcomes were measured and how the single-group findings should be interpreted.

Because the trial has no concurrent comparison group, its design is descriptive rather than a direct test against an alternative. The completed status indicates the record marks the study as completed; it does not establish that every planned outcome was reported or that the planned analyses were carried out.

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

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 Overall Response Rate (Complete and Partial Response) as Defined by RECIST 1.1, measured over Up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year.

The primary endpoint is the number of patients with an overall response, defined as a complete response or a partial response according to RECIST 1.1. A complete response means disappearance of all target lesions. A partial response means a >=30% decrease in the sum of the longest diameter of target lesions. Target lesions were assessed by MRI. The stated timeframe is up to 4 weeks after completion of study treatment, for total treatment time of up to 1 year.

Response endpoints are used in cancer studies to record whether measurable tumor lesions meet prespecified criteria for shrinkage or disappearance. A rule-based definition can make assessments more consistent than an informal judgment of improvement. Counting complete and partial responses together gives a binary endpoint: each evaluated participant is classified as having an overall response or not having one. The count is meaningful only alongside a clear denominator and information about who was assessed.

The registry record does not report the number of complete responses, partial responses, or overall responses. It also does not report a denominator for the primary endpoint or an estimate of uncertainty. Consequently, the endpoint definition can be described, but the response rate and its precision cannot be interpreted from this record. The primary outcome measure is a response count, not a direct measure of survival, symptom relief, or quality of life.

The response assessment timeframe also matters. Assessments made after treatment completion may depend on how long participants received treatment and whether they remained eligible for evaluation. The registry record does not describe handling of early discontinuation or missing imaging, so those features cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. A single-group study observes outcomes among participants receiving the study intervention without a concurrent control group. This can describe outcomes in the enrolled group, but there is no randomized contrast to isolate the effect of treatment. That limitation applies regardless of the statistical method used. For this study, allocation is listed as not applicable and masking as none.

What does the response count represent?

The primary measure is a count of patients with complete or partial response under RECIST 1.1. In general, a binary outcome assigns each participant to one of two categories, such as response or no response. To interpret a count, readers need to know the relevant analysis denominator and how missing or unevaluable assessments were handled. A proportion can then be estimated from the count and denominator. The registry record does not report the response count or primary endpoint denominator, so no response proportion can be interpreted from it.

RECIST 1.1 supplies operational criteria for classifying target-lesion change. The record defines complete response as disappearance of all target lesions and partial response as a >=30% decrease in the sum of the longest diameter of target lesions, assessed by MRI. Prespecified rules support reproducible classification, but consistency also depends on details such as image timing, measurement practices, and handling of incomplete assessments. Those details are not reported in the registry record.

What would an uncertainty interval add?

In general, a confidence interval describes a range of values compatible with the observed data under a statistical model and procedure. For a response proportion, it communicates how much uncertainty surrounds the estimate; a point estimate alone can make a small study appear more precise than it is. The interval would not correct the lack of a control group, nor would it establish causation. No confidence interval for the primary response outcome is reported in the registry record.

For binary outcomes, the choice of interval method can matter, particularly when counts are small or near the boundaries of possible values. Different methods may have different coverage properties. The record does not identify a method, and no recalculation is appropriate without the endpoint count and denominator. A result should not be reverse-engineered from enrollment or from safety counts, because these are not necessarily the primary endpoint analysis population.

How should the safety counts be read?

Safety counts are descriptive counts of participants with events among those at risk, as recorded for the treatment group. Serious adverse events and other adverse events are separate categories in the record. A count of participants with at least one event is not the same as a count of all event occurrences; a participant may have more than one event. The record does not provide detailed event terms or exposure time, so event-specific rates and comparisons cannot be evaluated.

For rare outcomes, a zero observed count does not imply zero underlying risk. General statistical reasoning recognizes that limited observation can leave substantial uncertainty about uncommon events. A larger or longer observation base may reveal events not seen in a small study. This is not a calculation of risk for this trial; the registry record does not supply enough information for such an estimate.

What do the planning illustrations mean?

Any sample-size planning illustration should be distinguished from the trial's actual design and results. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes an effect to detect as a stated fraction of the observed effect. Time-to-event illustrations refer to the total number of events; other illustrations refer to participants per arm. These are planning conventions, not observed trial findings.

The assumptions describe a hypothetical two-arm planning exercise, whereas this study is single-group and has no like-for-like control comparison. Such illustrations are not the study's sample-size justification, and the record does not report that justification. A sample-size calculation based on an observed effect is also not observed power. Power is a design property under assumed conditions; it should not be interpreted retrospectively as the probability that the study's result is true. The record does not report the numeric planning outputs or the effect estimate needed to appraise them.

What can be inferred from the reported analysis status?

The registry lists 0 analyses. In general, an outcome listing identifies what was intended to be measured, whereas an analysis supplies an estimate and often an uncertainty measure or test. Without the latter, readers cannot evaluate inferential claims. The record does not report the statistical model, hypothesis tests, adjustment strategy, or analysis population. No specific statistical test or model should therefore be attributed to this trial.

More generally, over-dispersion matters when count data vary more than a chosen model expects; ignoring it can make uncertainty appear too small. That concept is relevant to some count-data analyses, but the primary outcome is defined as a number of patients with response, and the registry record does not report a model that would require an over-dispersion assessment. It would be inappropriate to claim that over-dispersion was present or addressed.

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("Treatment (Akt Inhibitor MK2206)")
n      <- c(8)
events <- c(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  Treatment (Akt Inhibitor MK2206)  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 record lists the primary outcome of overall response rate and secondary outcomes of MK-2206-related adverse-event frequency, overall survival, and progression-free survival. It does not report an analysis plan, hypothesis-testing hierarchy, or adjustment for multiple comparisons. It is therefore not possible to determine whether the outcomes were intended to support separate formal claims, how multiple testing was handled, or whether any endpoint was prioritized beyond its designation as primary.

Multiplicity is a general concern when several outcomes or analyses are examined: the chance of at least one apparently unusual result can increase when many tests are conducted. Methods such as prespecifying a primary endpoint or adjusting test thresholds can address particular multiplicity questions, but the registry record does not say whether such methods were used. The outcome list alone does not establish which analyses were performed.

Missing data are also important for response assessment. Participants may lack a post-treatment MRI or may stop treatment before the planned assessment. The registry record does not report missing endpoint data, the number evaluated for response, an analysis population, or a method for classifying participants without an assessment. It is not possible to determine whether any missing data occurred or how they affected the endpoint.

The record lists 0 analyses. It does not report interim analyses, stopping rules, sensitivity analyses, or whether the planned and reported outcomes differed. These details are not reported in the registry record and should not be inferred. With no reported primary response result, denominator, or missing-data approach, robustness of the efficacy finding cannot be evaluated.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists 0 serious adverse events among 8 participants at risk. It also lists other adverse events among 8 participants at risk. These are participant counts as recorded, not a full account of event frequency over time. The record does not provide the event terms, grades, timing, duration, or number of repeated occurrences.

Serious adverse events and other adverse events are distinct categories in the registry record. The latter count should not be read as a count of serious events. A participant-level count also does not tell how many total event episodes occurred, since one participant can experience multiple events. The record does not provide details that would allow assessment of severity distributions or event-specific patterns.

Zero recorded serious adverse events in a small treated group is not proof that serious adverse events cannot occur. It describes what was recorded for the participants at risk during the reported observation, while the underlying risk remains uncertain. Exposure duration and follow-up time are not given in the safety summary, so rates adjusted for time at risk cannot be interpreted.

The registry record does not provide a comparison group, so the safety counts cannot establish whether events were more or less common than under another treatment or no treatment. They should be read as descriptive observations, not as evidence of a comparative safety effect.

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

The record describes a completed phase II study of MK-2206 in advanced refractory biliary cancers, using a single-group design and a response endpoint based on RECIST 1.1. It records enrollment of 8 and provides a schedule for oral treatment. For safety, it reports 0 serious adverse events among 8 at risk and other adverse events among 8 at risk. These are the specific findings that can be described from the posted information.

The primary response outcome itself is not reported in the registry record. Without the number of complete or partial responses, the relevant response denominator, and an uncertainty estimate, the posted record does not establish the observed response rate or its precision. Nor does it provide reported results for overall survival or progression-free survival. The trial's stated objective is not a substitute for outcome results.

Even with a response result, a single-group trial would not establish how outcomes compare with an alternative. Participants were not randomized to a control group, and the record identifies no comparator. Observed outcomes may reflect characteristics of the enrolled population, the course of disease, assessment procedures, and other factors as well as treatment. Statistical precision around a within-group estimate cannot remove this design limitation.

The record also does not provide enough information to assess the completeness of endpoint measurement, the handling of missing data, or the analytic choices used for any outcomes. These unknowns further restrict interpretation. The safety counts are similarly limited: they do not establish event rates over a defined exposure time or comparative safety.

Accordingly, the information supports a description of the trial's design and reported safety counts, but not a conclusion about the magnitude of tumor response or a causal treatment effect. It does not establish that treatment works or does not work. Those judgments require adequately reported outcome estimates and appropriate evidence for the question being asked.

14. Why This Trial Matters Statistically

This trial is statistically notable because its design illustrates the difference between describing outcomes and estimating a comparative treatment effect. A single-group study can record response and adverse events in the participants enrolled. It cannot provide the randomized, concurrent contrast that helps distinguish intervention effects from other influences. This distinction remains important even when the endpoint has a clear clinical definition.

The primary response endpoint uses a recognized rule-based framework, RECIST 1.1, with MRI assessment of target lesions. Such definitions can make the outcome more reproducible and help clarify what counts as a response. But precise endpoint wording does not by itself provide a result. In this record, the response count and analysis are not reported, so the endpoint cannot be quantified from the posted information.

The enrollment of 8 also highlights why precision matters. In general, estimates based on limited observations can be highly uncertain, particularly for binary outcomes. Reporting an estimate with an uncertainty interval helps readers distinguish a stable estimate from one compatible with a broad range of values. The record does not report such an estimate for the primary endpoint.

Finally, the record is useful for teaching the distinction between registry status, outcome listing, and analysis reporting. A study can be marked completed and list outcomes without presenting their estimates or inferential analyses. The reported safety counts are informative as descriptive counts, but they do not resolve uncertainty about rare events or establish comparative safety. Sound interpretation depends not only on study aims but also on complete outcome reporting and a design suited to the question.

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 important limitation for interpreting efficacy is that the registry record does not report the primary response count, endpoint denominator, or statistical estimate. Although the response definition and timeframe are stated, they are not enough to determine how many participants responded or how precise any estimate would be. Overall survival and progression-free survival are listed as secondary outcomes, but their results are not reported in the registry record.

The design is single-group, with no randomized or other comparator group. This prevents a direct comparison and limits causal interpretation of any observed outcome. The record also identifies no masking. It does not report whether response assessment was independently reviewed, how the assessment process was standardized, or how potential assessment bias was managed.

Enrollment was 8, while the primary endpoint analysis denominator is not reported. The record does not explain whether all enrolled participants were eligible for response assessment, whether any were unevaluable, or how missing imaging and early treatment discontinuation were handled. The safety counts do not resolve these uncertainties because a safety population and an efficacy analysis population need not be identical.

Safety reporting is limited to aggregate participant counts. The record does not supply adverse-event terms, severity grades, exposure time, or detailed follow-up. It therefore does not permit event-specific interpretation or time-adjusted rate assessment. A zero count for serious adverse events in this group cannot rule out uncommon harms.

Other limitations include the absence of reported statistical methods, analysis populations, multiplicity procedures, and interim-analysis information. The record lists 0 analyses. The full eligibility criteria and the distribution of participants across the listed disease conditions are not reported in the registry record. These gaps limit reproducibility, subgroup interpretation, and assessment of how broadly the findings could apply.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MK2206 in Treating Patients With Advanced Refractory Biliary Cancer That Cannot Be Removed by Surgery — NCT01425879.
• Registry record last updated 2016-06-17; status last verified 2016-05.
• Results first posted 2016-04-15.
• 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

This completed phase II study examined Akt inhibitor MK-2206 in refractory biliary cancers. The registry identifies a single-group design, no masking, and enrollment of 8. Treatment was oral on days 1, 8, 15, and 22, with courses repeated every 28 days while disease had not progressed and toxicity remained acceptable.

The primary endpoint was the number of patients with complete or partial response under RECIST 1.1, assessed by MRI. Its timeframe was up to 4 weeks after study treatment, for total treatment time of up to 1 year. The registry record does not report the primary response count, denominator, or analysis. Overall survival and progression-free survival are listed as secondary outcomes, but their results are not reported.

The safety summary records 0 serious adverse events among 8 at risk and other adverse events among 8 at risk. These counts are descriptive and do not provide a comparison with another group. The record lists 4 outcome measures and 0 analyses. Consequently, it supports description of the study design and recorded safety counts, but not an estimate of response or a comparative treatment conclusion.