Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond Progression in mCRC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond Progression in mCRC (NCT03099486), a na phase 2 study. The primary outcome is Progression Free Survival (PFS) at 2 Months.

2. Clinical Question

The clinical question is whether a regimen that retains regorafenib while adding 5-FU/LV can be evaluated in this selected setting after prior treatment progression. The study is identified as a pilot phase II trial, not a randomized comparison. Its single-arm design means the record can describe outcomes among those treated, but cannot directly compare those outcomes with an untreated group or another regimen within the trial.

The brief summary describes an intended enrollment of 15, whereas the registry lists enrollment of 2. The record status is terminated. It does not explain the reason for termination or provide enough outcome information to assess the primary question. Therefore, the registry entry establishes the question and the intended treatment context, but not a numerical estimate of the regimen’s effect.

3. Trial Design

The registry describes NCT03099486 as a pilot phase II, investigator-initiated clinical trial of regorafenib plus 5-FU/LV beyond progression on regorafenib monotherapy in metastatic colorectal cancer. The design is single group, open label, and has no allocation to a separate control arm. Allocation is recorded as not applicable, consistent with the absence of a randomized comparison.

The intervention list names regorafenib, 5-FU, and leucovorin. The brief summary describes oral regorafenib plus 5-FU/LV infusion. The listed treatment arm is titled “Regorafenib + 5FU/LV Treatment Arm.” No separate arm description is entered. The stated population had progressed on regorafenib monotherapy and prior standard multi-agent combination chemotherapy; the brief summary further refers to progression on 5-FU-containing chemotherapy combinations.

The trial is listed as phase 2. Its status is terminated. The registry lists a start date of 2017-10-06 and a primary completion date of 2020-06-02. The enrollment field gives 2, while the brief summary describes an intended study of 15 patients. The record does not explain the difference between those entries, the reason for termination, or whether the listed completion date represents completion of the planned enrollment or follow-up.

The primary outcome is titled “Progression Free Survival (PFS) at 2 Months,” with a 2-month timeframe. The record specifies a median parameter and a 95% confidence interval, but does not include a numerical estimate or interval. Secondary outcomes listed are overall survival rate, best overall response, and number of toxicities due to the combination. The registry record does not report numerical results for those outcomes in the information listed.

Because the study has no concurrent comparator, its design is suited to describing experience in the treated group rather than estimating a controlled treatment contrast. The record does not report a protocol-level statistical plan, detailed follow-up procedures, or the reason the trial was terminated.

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 Progression Free Survival (PFS) at 2 Months, measured over 2 months.

The primary outcome is progression-free survival (PFS) at 2 months. PFS generally describes the time until disease progression or death, according to the study’s endpoint definitions. In general, a fixed-time PFS outcome can describe whether participants remain alive without documented progression at a specified assessment time. The registry entry does not give the operational definition of progression, assessment schedule, censoring rules, or the analysis population used for this endpoint.

The outcome is relevant to the stated treatment setting because participants had already progressed on regorafenib monotherapy, and the trial evaluates adding 5-FU/LV while continuing regorafenib. A time-to-event outcome can incorporate the timing of progression or death rather than only recording whether an event occurred at the end of follow-up. In general, that can be useful when participants have different follow-up durations, provided the event and censoring information is collected and analyzed appropriately.

The registry specifies a median parameter and a 95% confidence interval, while the title and timeframe refer to PFS at 2 months. It does not report the numerical median, the confidence limits, or a numerical PFS result at that time point. The record therefore identifies the outcome and its planned summary form but does not permit interpretation of the size or precision of the observed primary result.

A confidence interval, in general, expresses the uncertainty around an estimated quantity under the analysis assumptions. Without the interval endpoints and the underlying estimate, neither the estimated PFS nor its precision can be assessed. The absence of a reported numerical result should not be taken as evidence for or against an effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes this as a single-group time-to-event trial. The primary outcome is PFS at 2 months, and the specified parameter is the median with a 95% confidence interval. No numerical result or analysis entry is listed. The method concepts below explain how such outcomes are generally interpreted; they do not establish which specific procedures were carried out in this trial.

What does a time-to-event outcome describe?

In general, a time-to-event outcome records the time from a defined starting point until an event of interest. For PFS, the event usually concerns progression or death, but the precise definitions depend on the study protocol. The registry record does not report the starting point, the criteria for progression, the assessment schedule, or how an event date was determined. Those details matter because differences in definitions or assessment can change when an event is recorded.

Some participants may not have a recorded event before their follow-up ends. In general, such observations may be censored: the analysis uses the information available up to the last known event-free time rather than treating the participant as having had the event. How censoring is handled and whether its assumptions are plausible are important for time-to-event analysis. The registry record does not report censoring rules, follow-up completeness, or a description of participants’ follow-up times.

What do the median and confidence interval mean?

In general, the median time-to-event is the time by which half of the estimated population has experienced the event, under the analysis method and assumptions. The registry specifies a median parameter for the primary outcome, but does not provide its numerical value. It also specifies a 95% confidence interval. A confidence interval describes uncertainty around an estimate under the method’s assumptions; it is not a guarantee that the true value lies within the interval in any particular trial.

For a fixed-time endpoint such as PFS at 2 months, an estimate can also be expressed as the probability of remaining alive without progression at that time. The record’s title and timeframe point to the 2-month assessment, but no numerical estimate for that assessment is reported. The wording that specifies a median parameter alongside a fixed-time title does not resolve how the sponsor presented or analyzed the endpoint. The analysis details are not reported in the registry record.

Why does the design affect interpretation?

In general, a single-arm study can describe outcomes observed among participants receiving a regimen. Without a concurrent control group, it cannot separate a treatment-associated outcome from other influences, such as the natural course of disease, prior treatment history, participant selection, or supportive care. A comparison with an external historical outcome would require a suitable, explicitly described reference and assumptions about comparability. No such comparison is reported in this record.

Open-label means the study is not masked, as recorded in the trial design. In general, awareness of treatment can affect some aspects of care and outcome assessment, especially when outcomes involve judgment. Whether this influenced the trial’s assessments is not reported. The record does not describe independent review or masking of outcome assessors.

What can planning calculations tell a reader?

In general, a sample-size calculation is a planning exercise: it describes how many observations might be needed under specified assumptions. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. Those assumptions do not turn this single-group trial into a two-arm comparison. Any planning figures based on such assumptions are illustrative, not observed power and not evidence about the trial’s outcome.

For time-to-event planning, the assumptions specify a total number of events using the Schoenfeld approach. In general, the number and timing of events can be more directly informative for time-to-event precision than enrollment alone, because participants may have different follow-up and event experience. The record does not report a numerical event target, an event count for the primary endpoint, or the details needed to assess a planning calculation. No additional calculation can be inferred from the listed assumptions.

Why is uncertainty especially important?

In general, an estimate from a small study can be highly uncertain, and the uncertainty depends on the observed data and analysis method. Enrollment alone does not determine the width of a confidence interval: event numbers, follow-up, censoring, and the distribution of event times also matter. Here the registry lists enrollment of 2 but reports no primary estimate or confidence limits, so the precision of the PFS result cannot be evaluated. A numerical comparison, a recalculation, or a claim about statistical significance is not supported by the information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, PFS at 2 months, and secondary outcomes for overall survival rate, best overall response, and number of toxicities due to the combination. It does not report numerical results for these outcomes in the information listed. The record lists no analysis entries, and it does not describe a multiplicity strategy for interpreting several outcomes or tests.

Multiplicity is a general statistical concern when many outcomes, time points, or comparisons are assessed. The more analyses considered, the greater the chance that an apparently notable result may arise by chance if the analyses are not accounted for in the interpretation. A prespecified hierarchy, adjustment, or clearly exploratory framing can help make that context transparent. Whether any such approach was planned or used is not reported in the registry record. It would not be appropriate to infer a correction method or a testing sequence.

The record does not report missing-data procedures, outcome-specific analysis populations, or how participants without a recorded endpoint assessment were handled. In general, missingness can affect the estimate if the availability of data is related to participants’ health or outcomes. For time-to-event analyses, incomplete follow-up and censoring require explicit definitions and assumptions. The registry entry does not provide enough information to assess these issues.

The listed enrollment and safety figures do not establish the analysis population for PFS or any secondary outcome. The record does not state whether analyses were based on all enrolled participants, participants who began treatment, or another defined group. Such population definitions are important for interpreting a trial result, but are not reported in the registry record.

11. 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: moderate congestive heart failure (50.0%).

The registry lists safety figures for the “Regorafenib + 5FU/LV Treatment Arm.” In the serious-event category, it records 2 at risk and 1 affected. In the other-event category, it records 2 at risk and 2 affected. The death count is listed as 2. The record also lists Moderate Congestive Heart Failure among the top serious terms, at 50.0%.

These are descriptive registry entries, not a comparison with a control group. The record does not give event onset dates, duration, severity details beyond the listed term, resolution status, or a causal assessment for each event. It also does not state whether the deaths were attributed to treatment, disease, or another cause. The categories should not be added together: the record does not establish whether the same participant appears in more than one category or how the categories relate.

In general, adverse-event counts describe events reported during a study and do not by themselves establish causation. The listed percentage for the serious term should be read as the registry’s reported figure, not as an estimate of comparative risk. With no concurrent comparator and limited reported detail, these figures do not support a treatment-versus-control safety comparison.

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

The result that can be interpreted from the registry is chiefly descriptive: this was a terminated, single-arm phase II pilot evaluating regorafenib plus 5-FU/LV after progression on regorafenib monotherapy in metastatic colorectal cancer. The registry lists enrollment of 2 and identifies PFS at 2 months as the primary outcome. It does not provide a numerical PFS estimate, confidence interval, or hazard ratio.

That absence means the size and precision of the primary outcome cannot be assessed from the record. It does not mean the treatment improved PFS, worsened PFS, or had no effect. No treatment-effect conclusion follows simply from the stated endpoint, the trial’s phase, or the fact that the study was terminated. The reason for termination is not reported in the registry record.

The study’s design also limits what its outcomes could establish. Because there is no concurrent comparator group, outcomes among treated participants cannot be directly contrasted with outcomes under another regimen within the trial. Any interpretation would need to account for the selected population, prior treatment, follow-up, and endpoint assessment. The record does not provide the numerical outcome data or methods needed to do so.

The safety entries report serious events, other events, a serious-event term, and deaths, but do not give sufficient detail to determine timing, cause, attribution, or overlap. They should not be read as proof that the combination caused an event, nor as a complete characterization of safety. The registry’s reported counts are limited descriptive information.

In general, a clinical trial can generate evidence only to the extent that its design and reported data support the intended inference. Here, the registry identifies a clinically specific question and provides some design and safety details, but lacks the numerical primary results and analysis information needed to answer that question. The record therefore cannot establish comparative efficacy or a definitive safety profile.

13. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a narrow clinical question and the limited outcome information in the registry. It concerns treatment after progression on regorafenib monotherapy, in a population also described as having progressed on standard multi-agent chemotherapy and 5-FU-containing combinations. Such a specific treatment history defines the population to which any result would apply; it also makes careful reporting of eligibility and analysis populations important.

The single-arm design is central to interpretation. In general, it can offer descriptive experience with a regimen in a selected group, but it does not provide a concurrent estimate of what would have happened under another treatment. A numerical outcome, even if reported, would not by itself establish a causal treatment effect. A control group or a carefully justified external comparison would be needed for a comparative claim, and no comparator is described in this record.

The registry lists enrollment of 2, while the brief summary describes an intended enrollment of 15, and the study status is terminated. These entries make transparent reporting of recruitment, follow-up, endpoint observations, and the reason for termination especially relevant. The record does not provide those explanations or a numerical primary result. It therefore illustrates why design descriptions and outcome estimates must be considered together rather than treating a stated objective as evidence of an observed effect.

From a biostatistical perspective, the lack of an estimate and confidence interval prevents assessment of both direction and precision. The absence of analysis entries also leaves key questions about censoring, missing data, and analysis populations unanswered. The record can identify the intended question and some reported safety counts, but it does not support a statistical conclusion about the regimen’s effect.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this trial affect interpretation of the registry entry. The design is single group and open label, with no separate comparator arm. Consequently, the record cannot provide a direct within-trial comparison of the combination against another treatment. The reason for selecting a single-arm design and the intended basis for interpreting outcomes are not reported in the registry record.

The registry lists enrollment of 2, while the brief summary describes an intended enrollment of 15. The record does not explain this difference, state the number treated, or identify the analysis population for the primary outcome. The trial is marked terminated, but the reason for termination and its implications for follow-up are not reported. The listed primary completion date does not by itself clarify whether endpoint follow-up was complete.

No numerical PFS result, confidence limits, hazard ratio, or analysis entry is listed. The record also omits the operational PFS definition, assessment schedule, censoring procedures, follow-up distribution, and handling of missing outcome information. Without these details, neither the estimated outcome nor its precision can be evaluated.

The safety information is limited to the recorded counts and a listed serious-event term. It does not provide event timing, individual attribution, cause of death, or enough detail to determine overlap between categories. Secondary outcomes are named but numerical results are not reported in the registry information listed. The record also does not report a multiplicity approach or protocol-level statistical plan. These omissions limit both clinical interpretation and independent statistical assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond Progression in mCRC — NCT03099486.
• Registry record last updated 2022-02-07; status last verified 2022-01.
• Results first posted 2022-02-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03099486 is listed as a terminated phase II, investigator-initiated, open-label, single-group pilot trial in metastatic colorectal cancer. It evaluates regorafenib plus 5-FU/LV after progression on regorafenib monotherapy. The registry lists enrollment of 2; the brief summary describes an intended enrollment of 15.

The primary outcome is PFS at 2 months, specified as a median with a 95% confidence interval. No numerical primary result, confidence limits, or analysis entry is reported in the registry information listed. Secondary outcomes include overall survival rate, best overall response, and toxicities due to the combination.

The registry lists serious and other adverse-event counts and two deaths, but does not report their causes or treatment attribution. The reason for termination, analysis populations, missing-data procedures, and detailed endpoint methods are not reported in the registry record.