Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer (NCT00504153), a na phase 2 study. The primary outcome is Progression-free Survival Rate.

2. Clinical Question

The clinical question is therefore a single-group assessment of progression-free status after dasatinib treatment, rather than a comparison of dasatinib with another treatment or with usual care. The posted design can describe outcomes among enrolled participants, but it cannot directly estimate a difference between treatment groups. The registry also lists response rate, somatic mutations, associations involving total and phosphorylated C-src expression and response, and change in plasma VEGF levels over 15 days as secondary outcomes. Those listings identify additional questions of interest; they do not, by themselves, establish what those outcomes were or whether they were analyzed.

The record identifies the study as phase II and completed. It does not report a numerical result for the primary progression-free survival rate. Consequently, the central question can be stated from the protocol description, but the posted registry information does not supply an estimate with which to answer it. No conclusion about treatment benefit can be drawn from the endpoint definition or the study design alone.

3. Trial Design

This was a phase II study sponsored by the National Cancer Institute (NCI), with a single-group model and no masking. The record lists allocation as NA, which is consistent with the absence of a randomized comparison group in the recorded design. Enrollment was 19. The study status is completed; the registry lists a start date of 2007-07 and primary completion of 2011-06.

Participants received oral dasatinib twice daily on days 1-28, with treatment repeating every 28 days unless disease progression or unacceptable toxicity occurred. The intervention list also includes laboratory biomarker analysis. The registry does not give further details of how the laboratory analyses were performed, or how biomarker findings were intended to influence treatment.

The primary outcome is named Progression-free Survival Rate and is expressed as a percentage of participants. Its description defines the count as the proportion alive and progression-free at 4 months. The record describes assessment at 4 months after completion of treatment, i.e., up to 12 months, and says progression would be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Participants alive without progression were to be censored at the date of their last negative examination.

The primary endpoint description also states that a Simon (1989), optimal, two-stage design would be employed. The stage boundaries, decision thresholds, and details of the design are not reported in the registry record. The posted record lists 5 outcome measures and 0 analyses. A participant flow account, exclusions from analysis, and the analysis population are not reported in the registry record. In a single-group study, the endpoint result would be interpreted as an outcome observed in the treated group, not as a randomized estimate of a treatment contrast.

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 Progression-free Survival Rate, measured over From the start of treatment to the time of disease progression or death from any cause, assessed at 4 months after completion of treatment (i.e., up to 12 months.).

The primary endpoint is the percentage of participants who are alive and have not experienced disease progression at the specified assessment point. In plain terms, it combines two events that would count against progression-free status: disease progression and death from any cause. The registry’s timeframe describes assessment at 4 months after completion of treatment, i.e., up to 12 months, while the endpoint description also refers to the proportion alive and progression-free at 4 months.

Progression-free survival is used in clinical trials because it captures the time until progression or death, rather than considering tumor response alone. A rate at a chosen time point gives a snapshot of the proportion meeting the endpoint definition at that point. It does not describe every participant’s individual course, and it is not interchangeable with overall survival or response rate.

The registry says progression would be evaluated using criteria proposed by the RECIST Committee. It also states that participants who remained alive without progression would be censored at their last negative examination. In general, censoring means that the event time is not observed beyond a participant’s last known assessment; it does not mean that the participant had no later event. How censoring was handled in the analysis is not reported in the registry record.

A numerical result for this primary endpoint is not reported in the registry record. Without an estimate, and without a confidence interval or other measure of uncertainty, the endpoint definition cannot establish the observed progression-free rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint descriptions provide some statistical context, but the registry does not report the complete statistical analysis plan or numerical primary result. The distinctions below explain what the recorded methods mean in general and what cannot be assessed from the registry record.

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who received the study intervention. It can estimate an outcome within that enrolled group if results are reported, but it does not create a direct treatment contrast. A randomized comparison helps balance measured and unmeasured prognostic factors on average between groups; no such comparison is recorded for this study. Thus, even a reported progression-free rate would not by itself show what would have happened to the same participants under another treatment.

The study is listed as phase II, single-group, unmasked, with allocation recorded as NA. These design features define important limits on interpretation. The registry does not report any additional design details that would allow a more specific account of how participants were selected for analysis or how assessments were conducted.

How should the primary endpoint be understood?

In general, progression-free survival concerns the time until disease progression or death, whichever occurs first. The registry describes the primary measure as a percentage of participants alive and progression-free at 4 months. A rate at a fixed assessment point differs from a median time-to-event result: it answers what proportion meets the specified status at that point, rather than identifying the time by which half the group has experienced an event.

The record says progression would be assessed using criteria proposed by the RECIST Committee. For participants still alive without progression, it specifies censoring at the last negative examination. In general, a censored observation indicates that the event was not recorded by the participant’s last known event-free assessment; the later event time is unknown. Time-to-event methods use censoring information rather than treating a censored participant as though the event could never occur. The specific analysis method used for this endpoint is not reported in the registry record.

The stated timeframe is assessment at 4 months after completion of treatment, i.e., up to 12 months. The registry also defines the progression-free count as the proportion alive and progression-free at 4 months. These descriptions are reproduced as recorded; further details resolving the timing and analysis window are not reported in the registry record.

What does the two-stage design statement tell readers?

The primary outcome description says that a Simon (1989), optimal, two-stage design would be employed. In general, a two-stage design can specify an early decision point, allowing a study to stop or continue based on accumulating outcome information. An optimal design is a design choice under particular assumptions and criteria. The label alone does not reveal the chosen thresholds, assumed rates, decision rules, or whether the planned stages were completed. Those details are not reported in the registry record.

The two-stage design statement should not be mistaken for a reported interim analysis. Whether interim analyses occurred, what decision rules were applied, and whether the design was followed are not reported in the registry record. The fact that the study is marked completed does not answer those questions.

What can uncertainty measures add?

In general, a confidence interval gives a range of values compatible with the data under a specified statistical method and assumptions. It helps readers judge how precisely an estimate has been measured. A point estimate without an interval can conceal substantial uncertainty, particularly when the study group is limited in size. No numerical primary endpoint estimate or confidence interval is reported in the registry record, so neither the estimated rate nor its statistical precision can be reviewed.

A hypothesis test or p-value would address a specified statistical hypothesis under stated assumptions; it would not by itself measure the size or clinical importance of an outcome. No primary endpoint test result is reported in the registry record. The number of listed analyses is 0, so the registry record does not document analysis results for the listed outcomes.

How should the planning illustration be read?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, significance level, allocation, and statistical method. The assumptions recorded for the planning illustration specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. This is a planning framework, not a report of a randomized two-arm design for this single-group study. The sample-size assumptions expressly describe the illustration as computed from the observed effect, not as the trial’s own design.

Planning sample sizes are not observed power. In general, observed power is not a substitute for reporting an effect estimate and its uncertainty. The registry record does not provide details of a sample-size justification for the actual trial, and the Simon design’s numerical assumptions and decision boundaries are not reported there. No sample-size value should be interpreted as a participant outcome or as evidence that the planned study had a particular probability of success.

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("Dasatinib (Tyrosine Kinase Inhibitor)")
n      <- c(19)
events <- c(1)
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  Dasatinib (Tyrosine Kinase Inhibitor)  19  1  5.3  0.1  26.0  0.9  24.6  1.2  24.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary progression-free survival rate and secondary measures concerning response, somatic mutations, C-src expression, and plasma VEGF. It records 0 analyses. No results of hypothesis tests, confidence intervals, or other inferential analyses are reported in the registry record.

When multiple outcomes or comparisons are tested, the chance of at least one apparently notable finding can increase. In general, multiplicity procedures can address that issue by adjusting the testing strategy or by identifying a primary analysis in advance. Whether any multiplicity adjustment, hierarchy, or other prespecified strategy was planned or used is not reported in the registry record. With no analysis results reported, statistical significance across outcomes cannot be evaluated.

The primary endpoint description states that participants alive without progression would be censored at the last negative examination. The specific approach to censored observations in the analysis is not reported in the registry record. The record does not report how missing endpoint assessments, incomplete follow-up, or withdrawals were handled, beyond the stated censoring description. The number and reasons for missing observations are not reported in the registry record.

The analysis population is not reported in the registry record. In particular, the record does not specify whether the primary analysis included all enrolled participants, only participants who began treatment, or another defined group. It also does not report how any protocol deviations or unevaluable participants were handled. These omissions limit the ability to reproduce the analysis or judge whether the reported participants, if results were available, correspond to the intended study population.

The two-stage design statement does not establish whether an interim analysis was conducted or what stopping boundaries were applied. Those details, as well as any changes to the statistical plan, are not reported in the registry 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: abdominal pain (10.5%), dehydration (10.5%), hypotension (10.5%), nausea (10.5%), urinary tract infection (10.5%).

The registry lists 19 participants at risk for serious adverse events and 19 at risk for other adverse events. It records 10 participants affected by serious adverse events and 17 affected by other adverse events. These are counts of participants recorded in each category, not measures of treatment effect. The categories should be read separately; the record does not state how many participants may have appeared in both.

The listed serious adverse event terms are abdominal pain, dehydration, hypotension, nausea, urinary tract infection, and vomiting, each shown as 10.5%. These percentages are reported as registry values. The record does not specify the number of events for each term, the duration or severity of each event, or whether the events were judged related to treatment. The listed terms do not necessarily represent every serious event in the study.

The deaths value is not reported in the registry record. It should not be interpreted as a count of zero. The safety figures are descriptive and do not establish whether dasatinib caused an event or whether the event rate would differ under another treatment. Because the study has no recorded comparator group, these counts cannot be used as a comparative safety estimate.

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

The registry record establishes that a phase II study of dasatinib was conducted in previously treated metastatic colorectal cancer using a single-group design. It defines a primary endpoint focused on the percentage of participants alive and progression-free at the specified assessment point. It also describes the treatment schedule, progression assessment approach, and some adverse-event counts.

What the record does not establish is the numerical primary endpoint result. That result is not reported in the registry record, nor is a confidence interval or other uncertainty measure reported. Without those data, readers cannot determine the observed progression-free rate or how precisely it was estimated. A completed study status does not fill that reporting gap.

The design also limits what any group outcome could mean. Without a comparator, the study cannot directly estimate the difference between dasatinib and another treatment. Outcomes in the treated group could reflect the intervention, characteristics of the participants, other influences, or a combination of these. The registry information does not allow those explanations to be separated.

The record’s safety counts describe participants affected by serious and other adverse events, and it lists several serious-event terms. These data do not establish causation, comparative risk, or the full clinical context of each event. The missing deaths value is not evidence that no deaths occurred.

In general, statistical interpretation depends on an estimate, its uncertainty, the analysis population, and the design. Here, the endpoint definition and design can be explained, but a quantitative efficacy interpretation is not possible from the registry information described. The study record should therefore be read as documenting a research question and selected design and safety details, not as sufficient evidence to determine whether the intervention changed outcomes.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported endpoint result are different things. The registry identifies progression-free status as the primary question and describes how progression was to be assessed. But a definition is not an estimate: without the observed rate and its uncertainty, readers cannot judge the magnitude or precision of the outcome.

It also demonstrates the interpretive limits of a single-group study. A group-level outcome can be informative as a description of participants treated in the study, but it does not provide a randomized treatment contrast. This distinction matters whenever study findings are discussed: an observed outcome and an effect attributable to treatment are not equivalent statistical claims.

The record’s two-stage design statement is another useful reminder that a design label is not a complete analysis plan. The Simon (1989), optimal, two-stage design is named, but its decision boundaries and numerical assumptions are not reported in the registry record. Without those details, the intended operating rules cannot be assessed.

Finally, the safety summary distinguishes participant counts from event descriptions. Counts of affected participants and percentages attached to event terms answer different descriptive questions, and neither alone establishes causation or comparative risk. Missing analysis, population, and missing-data details further limit reproducibility. These features make the record a useful example of how design, endpoint definition, result reporting, and uncertainty each contribute to statistical interpretation.

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 principal trial-specific limitation is the single-group design. Allocation is listed as NA, and no randomized comparator is recorded. As a result, an outcome in the treated group would not provide a direct estimate of a difference between treatments. The absence of masking is also recorded; the registry does not report whether or how this affected outcome assessment.

The enrollment was 19. The registry does not provide a numerical primary endpoint result or an uncertainty estimate, so the precision of any primary outcome cannot be assessed. The analysis population, participant flow, and handling of protocol deviations are not reported in the registry record. The record also does not give the number or reasons for missing endpoint assessments.

The endpoint description names RECIST-based progression assessment and censoring at the last negative examination for participants alive without progression. Further details on assessment timing, censoring methods, and analysis of time-to-event data are not reported in the registry record. The timeframe is described as assessment at 4 months after completion of treatment, i.e., up to 12 months, while the primary count is defined as the proportion alive and progression-free at 4 months; further clarification is not reported.

The registry mentions a Simon (1989), optimal, two-stage design but does not report its thresholds, assumptions, or implementation details. Interim analyses, changes to the analysis plan, and multiplicity procedures are not reported in the registry record. The safety information is also limited: attribution, event timing, severity details, and the deaths value are not reported. These limitations constrain both the interpretation and independent reproduction of the study’s analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dasatinib in Treating Patients With Previously Treated Metastatic Colorectal Cancer — NCT00504153.
• Registry record last updated 2014-05-19; status last verified 2011-10.
• Results first posted 2013-09-10.
• 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

NCT00504153 is a completed phase II study of dasatinib in previously treated metastatic colorectal cancer, sponsored by the National Cancer Institute (NCI). It used a single-group, unmasked design, with enrollment of 19. The registry lists oral dasatinib twice daily on days 1-28, repeating every 28 days in the absence of progression or unacceptable toxicity.

The primary endpoint was the percentage of participants alive and progression-free at 4 months, with progression assessed using criteria proposed by the RECIST Committee. The record describes censoring at the last negative examination for participants alive without progression and names a Simon (1989), optimal, two-stage design. A numerical primary endpoint result and its uncertainty are not reported in the registry record.

The registry lists 5 outcome measures and 0 analyses. It records 10 participants affected by serious adverse events and 17 affected by other adverse events, among 19 at risk in each category. The deaths value is not reported in the registry record. The single-group design does not provide a randomized treatment comparison.