A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial (NCT04786600), a randomized phase 2 study. The primary outcome is Overall Survival.

2. Clinical Question

3. Trial Design

This is a phase II randomized therapeutic optimization trial with a parallel-group design. The registry lists the University of Florida as sponsor, no masking, and an enrollment of 6. The recorded start date is 2022-03-14, the primary completion date is 2024-03-19, and the status is terminated. The reason for termination is not reported in the registry record.

Both groups used the same pre-specified sequence of FDA-approved drugs and drug combinations. The difference was the method used to guide movement through that sequence: the Signatera ctDNA assay in one group and imaging scans in the other. This makes the comparison one between treatment-guidance strategies. It is not described as a comparison of separate drug regimens.

The record identifies overall survival as the primary outcome, with a timeframe of 580 days. Best overall treatment response and progression-free survival are listed as secondary outcomes. The posted primary outcome rows show a count of 0 for the ctDNA assay-guided group, with a group count of 1, and a count of 0 for the scan-guided group, with a group count of 3. The registry record does not report an inferential analysis for the comparison. It also does not report why the posted group counts differ from the recorded enrollment.

The record does not report further details about randomization procedures, allocation concealment, eligibility criteria, or the rationale for stopping the trial. Those details should not be inferred from the trial title, phase, or status.

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 Survival, measured over 580 days.

Overall survival is the primary outcome named in the registry record, and its stated timeframe is 580 days. In general, overall survival concerns the time participants remain alive during follow-up. A time-to-event analysis typically uses information about when events occur and can account for participants whose event time is not observed during the available follow-up. The registry record does not report a detailed endpoint definition, event-censoring rules, or a time-to-event analysis method.

The posted primary result is represented as a count of participants with an event. It is 0 in the ctDNA assay-guided group, whose reported group count is 1, and 0 in the scan-guided group, whose reported group count is 3. The record does not explain the event coding in enough detail to reinterpret those values as a survival probability, median survival time, hazard ratio, or other time-to-event estimate. None of those comparative statistics is reported in the registry record.

Overall survival is commonly used because it captures a clinically important time-to-event outcome. Its interpretation depends on adequate follow-up and clearly specified handling of censoring. The registry record does not report those analysis details, so the posted counts alone do not describe how survival changed over time or how precisely the strategies compare.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group phase II trial without masking. Randomization is intended, in general, to make treatment groups comparable in expectation by assigning participants to strategies using chance. It does not guarantee balance in a trial with sparse posted group counts, and the registry record does not describe the randomization sequence, allocation concealment, or any stratification factors. The design compares guidance by ctDNA assay with guidance by imaging while the stated drug sequence is the same.

What does a participant event count show?

A binary outcome can be represented by counting participants who meet a defined event condition. The posted primary result is encoded as a count of participants with an event. Such a count needs a clearly defined event and a denominator representing the participants whose outcomes were assessed. The record names overall survival and gives a timeframe of 580 days, but it does not explain the event coding in detail. It reports counts of 0 with group counts of 1 and 3. Those values are not a rate, risk difference, odds ratio, or survival probability.

For a binary outcome, a comparative analysis would ordinarily estimate how often the defined outcome occurred in each group and quantify uncertainty around the contrast. General methods may include a confidence interval for a difference or ratio, depending on the outcome definition and analysis plan. A confidence interval describes the range of effect values compatible with the data under the method's assumptions; it is not a guarantee that the true value lies within the interval. No such interval or comparative estimate is reported in the registry record. Given the sparse posted counts, any estimate would need careful attention to its uncertainty.

How does overall survival differ from a simple count?

In general, overall survival is a time-to-event outcome. Its analysis uses information on how long participants were observed and whether the event occurred. Participants whose event is not observed during follow-up may be censored, meaning that their event time is only known to be later than their last observed time. Methods for time-to-event outcomes can incorporate this partial information, provided censoring assumptions and follow-up are handled appropriately. The registry record does not report whether censoring occurred, how it was defined, or which time-to-event method was planned or used. It therefore does not support reconstruction of a survival curve or a hazard-based comparison.

The timeframe of 580 days is reported, but a timeframe alone does not state that every participant was followed for that full period. The record does not report individual follow-up, event dates, or the number censored. A count at a stated timeframe cannot reveal whether events occurred early or late. Nor can it establish the shape of the survival experience across follow-up.

What can randomization and sample size calculations establish?

Randomization concerns assignment, while sample-size planning concerns how much information a study aims to collect to estimate or detect an effect. Planning illustrations are not observed power, and they do not describe the precision achieved in the trial. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects set as a stated fraction of the observed effect. For time-to-event outcomes, the planning convention is based on total events; other outcomes are expressed as participants per arm. No numerical planning estimates are reported in the registry record summarized for this trial. These assumptions should not be mistaken for a reported design justification or for the trial's own statistical plan.

General sample-size calculations depend on assumptions about the effect to detect, outcome variability or event frequency, allocation, and the statistical method. If observed effects are used to illustrate future planning, the estimates are conditional on those observed effects and can be unstable when the underlying data are sparse. They do not establish that the trial had adequate power, and they do not repair the absence of a comparative analysis. The registry record does not report a sample-size justification or a planned target effect.

Why is the comparison not recalculated?

A simple unadjusted recalculation requires enough clearly defined summary information for both groups. Here, the posted primary outcome values are counts, the group counts are sparse, and the event definition is not detailed. The registry record indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. Accordingly, no recalculated comparison should be treated as a result. The sponsor's analysis does not take precedence on the basis of a reported discrepancy, because the record does not indicate such a discrepancy; however, the sponsor's own analysis is not reported in the registry record.

More generally, a recalculation from summary statistics cannot substitute for a prespecified adjusted analysis when adjustment is needed, and it cannot recover participant-level information that is not posted. The registry record reports no analyses and gives no statistical analysis plan. The choice of model, treatment of missing values, covariate adjustment, and rules for interpreting multiple outcomes are not reported in the registry record.

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("ctDNA Assay-guided Intervention", "Scan-guided Intervention")
n      <- c(1, 3)
events <- c(0, 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  ctDNA Assay-guided Intervention  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Scan-guided Intervention  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists overall survival as the primary outcome and best overall treatment response and progression-free survival as secondary outcomes. Considering several outcomes can raise a multiplicity issue: in general, the more statistical tests performed, the greater the chance of obtaining at least one apparently notable result by chance. A prespecified hierarchy or adjustment can address some multiplicity concerns. The registry record does not report a testing hierarchy, multiplicity adjustment, or analysis plan, and it reports no analyses.

The record does not report an analysis population, such as whether analyses were planned according to randomized assignment or according to treatment received. It also does not describe exclusions, participant disposition, or which participants contributed to each outcome. The recorded enrollment is 6, while the posted primary result rows have group counts of 1 and 3. The reason for the difference is not reported in the registry record.

Missing-data procedures are not reported in the registry record. For overall survival, the record does not state how incomplete follow-up or censoring was handled. For the secondary outcomes, outcome values, denominators, and missingness information are not reported in the registry record. Without these details, the extent and potential influence of missing information cannot be assessed.

These omissions limit interpretation of the posted results. They prevent assessment of whether comparisons followed a prespecified plan, whether all randomized participants were included, and whether the reported counts represent complete outcome ascertainment.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thromboembolic event (100.0%), abdominal infection (33.3%), small intestinal perforation (33.3%).

The serious adverse event summary reports the ctDNA assay-guided group with 1 participant at risk and 1 affected, and the scan-guided group with 3 participants at risk and 2 affected. These figures describe the counts recorded in the registry; they are not a randomized comparison adjusted for follow-up or other factors. The record also reports deaths of 1 in the ctDNA assay-guided group and 3 in the scan-guided group. The registry does not explain the relationship between these death counts and the primary outcome event coding.

The listed serious adverse event terms are thromboembolic event at 100.0%, abdominal infection at 33.3%, and small intestinal perforation at 33.3%. The basis for the displayed percentages is not reported in the registry record. The reported term percentages should therefore be read alongside the limited group counts, not as precise estimates of event frequency in a broader population.

The other adverse event summary reports 1 at risk and 1 affected in the ctDNA assay-guided group, and 3 at risk and 3 affected in the scan-guided group. Adverse event counts are descriptive. With sparse group counts and no reported comparative safety analysis, they do not establish whether one strategy has a higher or lower safety risk.

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

The posted record documents a randomized comparison of ctDNA assay-guided and scan-guided treatment decisions for refractory metastatic colorectal cancer. It identifies overall survival as the primary outcome and lists progression-free survival and best overall treatment response as secondary outcomes. The primary outcome result is posted as a count of 0 in each group, alongside group counts of 1 and 3.

Those data do not provide a precise estimate of the difference between strategies. The record reports no confidence interval, significance test, survival curve, or comparative estimate. The primary outcome event is not defined in detail, and the reason the posted group counts differ from the enrollment of 6 is not reported. Consequently, the counts should not be read as evidence of equivalence or as a reliable estimate of the size of a treatment-strategy effect.

The registry's terminated status is a description of trial status, not an explanation for the posted results. The reason for termination and the planned analysis are not reported in the registry record. The absence of a reported comparative analysis also means the record cannot establish whether any observed difference is compatible with chance, or how uncertain a potential difference would be.

The safety figures and serious adverse event terms are also descriptive. Their sparse counts and unreported percentage basis limit comparison. The registry record does not establish that one strategy is safer or less safe.

Overall, the record offers limited descriptive information about the study and its posted outcomes. It does not support a conclusion about the benefit or lack of benefit of either treatment-guidance approach. More complete outcome definitions, participant accounting, follow-up information, and analyses would be needed to interpret comparative effects and their precision.

14. Why This Trial Matters Statistically

This trial raises a statistical question about how treatment decisions are guided: by a ctDNA assay or by imaging, while using the same stated sequence of drugs and drug combinations. Framing the comparison this way helps separate the strategy for changing treatment from the named treatment sequence itself. It also makes the outcome definitions and decision rules important to interpretation.

The registry identifies overall survival as primary, with progression-free survival and best overall treatment response also listed. These endpoints describe different aspects of outcome, and a prespecified plan is important when several outcomes are considered. The registry record does not report such a plan or any inferential analyses. That absence matters because outcome selection, analysis methods, and multiplicity handling affect how comparative results should be interpreted.

The posted primary counts are very sparse, and the group counts do not account for the recorded enrollment. This highlights why participant flow, follow-up, and missing-data reporting are essential: without them, readers cannot determine how the posted outcomes relate to trial enrollment or assess the precision of the comparison.

The trial's statistical importance therefore lies in the design question and the limits of the available record, rather than in a conclusive numerical comparison. Clear reporting of treatment-guidance rules, event definitions, follow-up, analysis populations, and uncertainty would be necessary to evaluate the randomized comparison. The posted data do not establish that either strategy is superior, equivalent, or safer.

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 registry record contains limited information for evaluating the trial's comparative results. The posted primary outcome is a count of 0 in each group, with group counts of 1 and 3, while recorded enrollment is 6. The reason for this difference is not reported in the registry record. Without participant disposition, it is not possible to determine how the posted counts relate to the enrollment.

The primary endpoint is named overall survival and the timeframe is 580 days, but the record does not report a detailed event definition, follow-up distribution, censoring rules, or survival analysis method. The posted counts therefore cannot be translated into a time-to-event estimate. No comparative estimate or measure of uncertainty is reported.

Although progression-free survival and best overall treatment response are listed as secondary outcomes, their numerical results are not reported in the registry record. The record reports no analyses, and it does not report a statistical analysis plan, analysis population, multiplicity approach, or missing-data procedures. The reason for the terminated status is also not reported.

The safety summaries have sparse counts, and the basis for the listed serious adverse event percentages is not reported. These descriptive figures cannot support a reliable comparative safety assessment. In combination, these limitations make the record insufficient for estimating the comparative effects or precision of the two treatment-guidance strategies.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Randomized Therapeutic Optimization Trial for Subjects With Refractory Metastatic Colorectal Cancer Using ctDNA: Rapid 1 Trial — NCT04786600.
• Registry record last updated 2025-07-01; status last verified 2025-06.
• Results first posted 2025-07-01.
• 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

NCT04786600 is a randomized, open-label, parallel-group phase II trial sponsored by the University of Florida. It compares treatment decisions guided by the Signatera ctDNA assay with decisions guided by imaging scans, using the same stated sequence of FDA-approved drugs and drug combinations. The condition is metastatic colorectal cancer, and the title describes the population as having refractory disease.

The registry records enrollment of 6, a start date of 2022-03-14, a primary completion date of 2024-03-19, and terminated status. Overall survival is the primary outcome, with a stated timeframe of 580 days; best overall treatment response and progression-free survival are listed as secondary outcomes.

The posted primary outcome count is 0 in each group, with group counts of 1 and 3. No inferential analyses are reported. The reason for termination, participant accounting, detailed endpoint definitions, analysis methods, and numerical secondary outcome results are not reported in the registry record.