Enzastaurin for Patients With Metastatic Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enzastaurin for Patients With Metastatic Colorectal Cancer (NCT00192114), a na phase 2 study. The primary outcome is Percentage of Participants With Progression Free Survival (PFS) at 6 Months.

2. Clinical Question

This is a descriptive question about outcomes in the study group, not a randomized comparison of enzastaurin against another treatment. Without a comparator, the registry information cannot separate the observed clinical course from what might have occurred without the study drug or with another approach. The posted record also does not report a numerical primary endpoint result, so it cannot establish the level of six-month progression-free survival observed in these participants.

3. Trial Design

The registry identifies this as a Phase 2 study of oral enzastaurin HCl in participants with metastatic colorectal cancer. It lists a single-group model, allocation as NA, and no masking. Enrollment is recorded as 28. The study status is completed; the listed start and primary-completion dates are 2005-08 and 2008-03. These record details describe the study's structure and timing but do not supply an outcome estimate.

The brief summary describes daily enzastaurin for participants with Stage 4 colorectal cancer who had not received prior chemotherapy for advanced colorectal cancer. The intervention entry names enzastaurin HCl, while the arm description contains no additional information. The registry does not report a separate control arm or a randomized treatment allocation. Accordingly, the study is best read as a single-group assessment, rather than as a like-for-like comparison between treatment groups.

The primary endpoint is the percentage of participants with progression-free survival at six months. The registry also lists outcomes concerning objective response, overall survival, progression-free survival, stable disease, response timing and duration, adverse events or death, and change in QTc interval. There are twelve outcome measures recorded, but the numerical primary outcome and detailed results for the other listed outcomes are not reported in the registry record used for this analysis.

The endpoint population is described as all randomized participants who received at least one dose of study drug, with five censored participants. That wording is not readily aligned with the same record's single-group model and allocation marked NA. The record does not clarify this terminology or provide a fuller analysis-population account. The distinction matters because the study-group definition and handling of participants determine which observations contribute to an outcome estimate.

No protocol details, dose amount, eligibility criteria beyond the summary description, or statistical analysis plan are reported in the registry record. The study's structure therefore supports a descriptive reading of outcomes among treated participants, but the record does not establish the additional design details needed to assess all potential sources of bias or analytic choices.

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: Participant flow reports those who discontinued from study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study drug. Censored participants =5

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 enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Progression Free Survival (PFS) at 6 Months, measured over Baseline to 6 months.

The primary endpoint is the percentage of participants with progression-free survival at six months, with the timeframe defined as baseline to six months. The registry defines progression-free survival as the time from the first dose of enzastaurin to the first documented progressive disease or death from any cause, whichever occurs first. It defines progressive disease using RECIST v1.0: an increase of at least 20% in the sum of the longest diameters of target lesions, using the smallest recorded sum since treatment began as the reference, or the appearance of one or more new lesions.

A six-month progression-free survival percentage is a time-specific summary: it counts participants who are alive and have not had documented progression by that point, relative to the treated participants identified in the endpoint definition. It can be useful because it expresses disease-control status at a clinically interpretable time rather than only reporting a continuous time-to-event measure. That general explanation does not imply that this endpoint alone captures every aspect of a participant's clinical course.

The registry says that participants without known death or progression were censored at their last progression-free assessment under specified circumstances, including subsequent systemic anticancer therapy before progression or death. Censoring means an observation contributes information up to a recorded point without being treated as an observed progression or death at that point. The record reports five censored participants, but does not provide the event count or the numerical six-month percentage. The endpoint result and its confidence interval are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study's single-group structure determines the kind of statistical question that can be addressed. The registry lists one enzastaurin HCl group, allocation as NA, and no masking. A single-group estimate describes outcomes in the enrolled study population. It does not estimate a treatment contrast against a concurrent control. General statistical principle: a comparison with a control can help distinguish a treatment-associated difference from background variation and other influences; without that comparison, observed outcomes are descriptive and causal interpretation is limited.

What does the primary endpoint estimate?

The primary endpoint is the percentage of participants with progression-free survival at six months. In general, a percentage endpoint expresses the frequency of a defined status in a specified population. Here the status is being alive and free of documented progression at the six-month point, according to the endpoint definition. The record describes the denominator as treated participants and describes the endpoint population as all randomized participants who received at least one dose. Since the study is also recorded as single-group with allocation NA, that population wording is not fully clarified.

For time-to-event outcomes, the endpoint is based on when an event occurs, rather than merely whether an event was ever recorded. The event in this study is the first of documented progressive disease or death from any cause. The registry uses RECIST v1.0 criteria to define progression, including an increase of at least 20% in the sum of the longest diameters of target lesions from the smallest sum recorded since treatment began, or the appearance of one or more new lesions. This operational definition helps specify what counts as progression, but it does not give the observed event data.

What does censoring mean?

General statistical explanation: censoring occurs when a participant's event time is not observed in full. The participant can contribute information through the last point at which event-free status is documented, without being assigned an event at a later unobserved time. The registry specifies censoring at the last progression-free disease assessment in certain situations, including when a participant was not known to have died and had no documented progression by the data-inclusion cut-off, or when subsequent systemic anticancer therapy began before progression or death.

The registry reports five censored participants. That count alone does not show when censoring occurred, why each participant was censored, or whether those participants differed from participants whose outcomes were observed. General statistical principle: time-to-event estimates rely on assumptions about the relationship between censoring and the likelihood of an event. The record does not provide the participant-level follow-up needed to examine those assumptions. The actual six-month estimate and confidence interval are also not reported in the registry record.

How should the confidence interval be understood?

The primary endpoint lists a 95% confidence interval as its dispersion measure. In general, a confidence interval communicates the statistical uncertainty around an estimated quantity under the method used to construct it. It does not account automatically for every source of bias, and it is not a guarantee that the interval contains a true value. The registry record gives the planned form of uncertainty reporting but not the numerical estimate, interval limits, or calculation method. Consequently, precision cannot be assessed from the posted endpoint description alone.

The enrolled group size is 28. General statistical principle: the amount of information available, the frequency of events, and the amount and pattern of censoring all influence the precision of time-to-event estimates. No precision value can be derived from enrollment alone, and no such calculation is made. The endpoint's confidence interval must be read from a reported estimate rather than inferred from the group size.

What can the planning illustrations tell readers?

The registry's sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect is a stated fraction of the observed effect. For time-to-event tables, the stated approach gives a total event count; other illustrations are expressed as participants per arm. These are planning assumptions, not a description of the actual single-group study design and not observed power.

Because the numerical observed effect and the resulting planning values are not reported in the registry record, no specific planning requirement can be interpreted. General statistical explanation: planning calculations depend on assumptions about the effect to detect, variability or event rates, significance threshold, and design. Changing those assumptions changes the planning result. Such illustrations do not retrospectively establish that an actual study had adequate power, nor do they replace the observed estimate and its uncertainty.

Why does the analysis population matter?

The record describes the endpoint population as all randomized participants who received at least one dose. In a single-group study with allocation marked NA, the use of the word randomized raises a reporting ambiguity. It is not possible to determine from the registry wording whether this is a standard population label carried over from another format or a precise account of how participants were selected for analysis. General statistical principle: a result's population definition affects its interpretation, particularly if enrolled, treated, and analyzed participants differ. The record does not report a participant flow or further explanation.

Overall, the available method information specifies the endpoint, event definition, censoring rules, confidence-interval type, and general assumptions used for planning illustrations. It does not provide the numerical endpoint result, interval limits, full analysis plan, or participant-level follow-up. Statistical interpretation should remain within those boundaries.

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("Enzastaurin HCl")
n      <- c(28)
events <- c(8)
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  Enzastaurin HCl  28  8  28.6  13.2  48.7  15.3  47.1  15.3  47.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists twelve outcome measures, including the primary six-month progression-free survival endpoint and outcomes related to response, survival, stable disease, adverse events, and QTc change. Considering multiple outcomes can raise a multiplicity issue: when many statistical questions are assessed, the chance of at least one apparently notable finding can increase. General statistical explanation: a prespecified testing strategy may address that issue, for example by identifying a primary outcome or defining how secondary analyses will be interpreted. The registry record does not report a multiplicity adjustment or a detailed testing hierarchy, so it is not possible to determine how multiple outcomes were handled.

The record identifies the primary endpoint and its 95% confidence interval as the dispersion measure, but does not provide the numerical estimate or interval. It also records zero analyses. The listed secondary outcomes therefore should not be treated as reported findings; their numerical results are not reported in the registry record. The presence of outcome names alone does not reveal whether each was assessed, how it was analyzed, or whether any analysis was prespecified.

For missing or incomplete follow-up, the record gives a censoring count of five and describes censoring rules for progression-free survival. It does not provide a fuller account of missing observations, reasons for missingness, follow-up duration by participant, or sensitivity analyses. Censoring is not the same as an observed event, and the effect of censoring depends on the information available and the assumptions used in analysis. The posted record is insufficient to evaluate those assumptions.

The endpoint population wording refers to randomized participants who received at least one dose, while the design is recorded as single-group with allocation NA. No further analysis-population definitions or participant flow are reported in the registry record. These omissions leave uncertainty about the exact analysis set and how participants entered it. No inference about imputation, exclusions, interim analyses, or a prespecified statistical plan is warranted from the record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute myocardial infarction (3.6%), cardiac failure (3.6%), gastrointestinal obstruction (3.6%), infection (3.6%), pneumonia (3.6%).

The adverse-event summary lists 28 participants at risk for the enzastaurin HCl group. It records 4 participants affected by serious adverse events and 22 affected by other adverse events. These are counts within the study group, not comparisons with another treatment group. The number of deaths is not reported in the registry record's adverse-event group information.

The listed serious adverse-event terms are acute myocardial infarction, cardiac failure, gastrointestinal obstruction, infection, pneumonia, and dehydration. Each term is accompanied by a reported value of 3.6%. Those percentages describe the registry's term-level entries; they should not be added together or treated as a percentage of participants with any serious event. Participants may contribute more than one event term, and the record does not give the participant-level overlap or event counts for each term.

General statistical explanation: safety summaries depend on how events are defined, collected, coded, and attributed, and on the time participants were observed. The registry excerpt does not provide those details or a full account of event timing and exposure. The serious and other adverse-event summaries can therefore describe what is listed, but do not establish comparative safety or explain the cause of any event. A missing death count should not be interpreted as zero deaths.

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

The record establishes that a completed Phase 2, single-group study assessed oral enzastaurin HCl in participants with metastatic colorectal cancer, with enrollment of 28. It specifies a primary endpoint of progression-free survival at six months and defines progression using RECIST v1.0 criteria. Those details help clarify what the study set out to measure and how a progression event was defined.

The numerical primary outcome is not reported in the registry record. As a result, readers cannot determine from this record what percentage of treated participants were alive and progression-free at six months, or how precise that estimate was. A defined endpoint and an enrollment count do not substitute for the outcome estimate and its confidence interval. The listed five censored participants add context about follow-up but do not supply the missing result.

The single-group design also limits the conclusions that could be drawn even if a descriptive outcome estimate were available. Without a listed concurrent comparator, an observed outcome cannot be interpreted as a treatment effect relative to another option. It cannot distinguish the contribution of enzastaurin from the underlying course of disease, participant selection, other care, or study procedures. No conclusion that the treatment works or does not work follows from the information reported.

The safety summary records serious adverse events in 4 participants and other adverse events in 22 participants, with six serious-event terms listed at 3.6% each. These data describe reported events in the study group. They do not show how event frequency would compare with another group, and the record does not report the death count in the adverse-event group information. The event-term percentages are not a complete measure of an individual's overall risk.

In short, the record supports a description of the study design, endpoint definition, censoring information, and listed safety summaries. It does not support a numerical interpretation of the primary efficacy endpoint or a comparative conclusion about efficacy or safety. Those limits reflect what is reported, rather than evidence that an unreported result had a particular value.

14. Why This Trial Matters Statistically

This study illustrates why statistical interpretation begins with design, not merely with an endpoint label. A single-group study can describe outcomes among treated participants, but it does not supply a concurrent contrast. Recognizing that distinction prevents a within-group outcome from being mistaken for evidence of a comparative treatment effect. The record explicitly lists a single-group model, allocation as NA, and no masking, making the design context central to any reading of the results.

The endpoint definition also matters. Progression-free survival combines progression and death into a time-to-event outcome, and the registry specifies how progression is identified using RECIST v1.0. A clear event rule supports consistent interpretation of what the endpoint is intended to capture. Yet a detailed definition cannot replace the observed estimate, event data, or uncertainty interval. Here, the numerical six-month endpoint result is not reported in the registry record.

Censoring highlights another important issue in clinical statistics: outcome status may be known only up to a participant's last assessment. The registry reports five censored participants and describes some censoring circumstances. A censoring count is informative but incomplete; the timing, reasons, and assumptions behind censoring also influence interpretation. This record does not provide enough detail to evaluate those features.

The record also offers a useful example of why safety counts need careful framing. Serious and other adverse events are reported within a study group, alongside term-level percentages. Such summaries describe the recorded experience but do not establish comparative risk. The absence of a reported death count must remain distinct from a claim that no deaths occurred.

Finally, the presence of multiple listed outcomes and planning assumptions does not reveal the analysis plan or establish study power. The record reports twelve outcome measures and describes general assumptions for planning illustrations, but it does not report numerical outcome analyses. Careful statistical reading separates endpoint definitions, observed results, uncertainty, design limitations, and planning calculations. When one of those components is absent, conclusions must remain correspondingly narrow.

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 primary limitation is that the registry record does not report the numerical value of the primary six-month progression-free survival endpoint or its confidence interval. The endpoint's definition is detailed, but the absence of its result prevents assessment of the observed percentage and precision. The record also does not report numerical findings for the listed secondary outcomes.

The single-group structure is an important design limitation for interpretation. There is no separate comparator group listed, so the record cannot provide a contemporaneous contrast. The study's outcomes, even if reported, would describe the participants' experience rather than identify what would have happened to comparable participants under another treatment. The record does not give information that would resolve this limitation.

The endpoint population description refers to all randomized participants who received at least one dose, while the design is listed as single-group and allocation as NA. The record does not explain this wording. It also does not provide a participant flow, analysis-set details, or information about exclusions. The exact relationship between enrollment and the analysis population is therefore not fully documented.

Five participants are recorded as censored for the primary endpoint, but the timing and participant-level circumstances are not reported. The record does not provide follow-up distributions or sensitivity analyses to assess the impact of censoring. It also does not provide the full protocol, detailed statistical plan, or information about interim analyses. These elements should not be inferred from the endpoint description or study status.

For safety, the record provides summary counts and serious-event terms but does not give event-level timing, overlap among affected participants, or a death count. The group summaries cannot support a comparative safety assessment. These limitations constrain interpretation of both the efficacy endpoint and the safety information without implying any unreported result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Enzastaurin for Patients With Metastatic Colorectal Cancer — NCT00192114.
• Registry record last updated 2020-08-06; status last verified 2020-07.
• Results first posted 2020-08-06.
• 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

The record describes a completed Phase 2, single-group study of oral enzastaurin HCl in participants with metastatic colorectal cancer. Enrollment is 28; the registry lists no masking and allocation as NA. The brief summary characterizes the population as having Stage 4 disease and no prior chemotherapy for advanced colorectal cancer.

The primary outcome is the percentage of participants with progression-free survival at six months, defined using documented progression or death. Five participants are listed as censored. The numerical primary result and its 95% confidence interval are not reported in the registry record.

The safety summary records 4 participants with serious adverse events and 22 with other adverse events among 28 at risk. Six serious-event terms are listed at 3.6% each. A death count is not reported in the adverse-event group information. The single-group design and absent numerical primary outcome limit interpretation to the reported study description and safety summaries.