TAS-OX for Refractory Metastatic Colon Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for TAS-OX for Refractory Metastatic Colon Cancer (NCT02848079), a na phase 1, phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

The clinical question is whether the combination can be assessed for safety and antitumor activity in patients with metastatic colorectal cancer after progression or recurrence following FOLFOX chemotherapy. The registry summary describes those aims, but the posted record does not give numerical results for the primary outcome. It therefore does not show the estimated response rate or its precision.

This design addresses outcomes observed in one treatment group. Without a concurrent comparison group, outcomes cannot by themselves establish how the combination compares with another treatment or with no treatment. Differences in patient characteristics, disease course, and other factors cannot be separated from treatment effects through a randomized between-group comparison in this record.

Progression-free survival and overall survival are listed as secondary outcomes. Their numerical results are not reported in the registry record. The response criteria are described, but the record does not report the assessment results needed to interpret the frequency of response.

3. Trial Design

The registry record describes TAS-OX as a single-group Phase 1 and Phase 2 study. It lists 41 enrolled participants, no masking, and allocation as NA. The sponsor is Yale University, and the study status is completed. The recorded study start is 2016-10-31, and the primary completion date is 2020-06-02.

The intervention is a combination of TAS-102 and oxaliplatin. TAS-102 is described as oral, while oxaliplatin is given by infusion. The record says that Part 1 treatment began at level 1 doses based on prior clinical experience, but the available arm description is truncated and does not provide a complete account of dosing or subsequent treatment procedures. Further protocol details are not reported in the registry record.

A single-group design can describe what happened among participants receiving the study treatment. It does not create a like-for-like control group. The registry record itself notes that this is not a randomized comparison and that arms are not a like-for-like control comparison. Because no separate comparator is listed, the trial record cannot provide a randomized estimate of the difference between TAS-OX and another treatment.

The primary outcome is Overall Response Rate, assessed by RECIST 1.1, with a timeframe of up to 30 days following discontinuation of treatment. Progression Free Survival and Overall Survival are listed as secondary outcomes. The record lists three outcome measures and zero analyses, but does not report numerical outcome findings. It also does not report a sample-size justification, a detailed statistical analysis plan, or details of any interim analyses.

The registry record includes planning illustrations based on the observed effect, with assumptions for a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions, not evidence that this single-group study used a two-arm design. They are not the trial's own design justification or observed power.

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

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT)

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate, measured over up to 30 days following discontinuation of treatment.

Overall Response Rate is the registry's named primary endpoint. The description says it is evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with tumor assessment by CT or MRI. Complete Response is defined as disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions. Overall response combines complete and partial response.

As a general statistical concept, a response rate describes the share of an analyzed population meeting a prespecified response definition. It can be useful for summarizing tumor shrinkage during a defined assessment period, especially when the clinical question concerns whether tumors meet objective response criteria. It is different from a time-to-event endpoint, which measures time until an event or censoring, and from survival outcomes, which concern time to progression or death.

The registry record specifies the ITT population and an assessment timeframe of up to 30 days following discontinuation of treatment. However, it labels the endpoint with the unit months, parameter MEDIAN, and dispersion as a 95% Confidence Interval. Those labels do not align conceptually with a response rate, which is ordinarily expressed as a proportion. The record does not give a numerical response estimate, responder count, or confidence interval, so the result and its precision cannot be interpreted from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint represent?

The primary endpoint is named Overall Response Rate. Its description uses RECIST 1.1 criteria to classify tumor findings as complete response, partial response, or neither. Complete Response means disappearance of all target lesions, while Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions. The overall response definition combines the first two categories.

As a general statistical explanation, a response rate is a proportion: it relates the number meeting the response definition to the population being analyzed. To interpret an estimate, readers generally need both the numerator and denominator, the assessment rules, and an uncertainty interval. The registry identifies ITT as the analysis population and gives a timeframe, but does not report a response count, rate, or interval. The numerical response result therefore cannot be evaluated from this record.

Why do the endpoint labels need care?

The record attaches the labels MEDIAN and months to Overall Response Rate, and names a 95% Confidence Interval as the dispersion measure. A median in months usually describes a time quantity, whereas a response rate describes a proportion. This is a conceptual mismatch between the endpoint description and its statistical labels. The record does not explain whether the labels are registry metadata or reflect a different intended measure, so no alternative interpretation should be assumed.

What does a confidence interval mean?

In general, a confidence interval communicates uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater statistical precision than a wider one, while the interval's location describes which values remain compatible with the data and method. It does not guarantee that the true value lies inside a particular interval, nor does it correct a biased design or incomplete measurement. No numerical interval for the primary outcome is reported in the registry record.

How should the time-to-event outcomes be read?

Progression Free Survival and Overall Survival are listed as secondary outcomes. In general, time-to-event methods account for the time until an event and may also use information from participants whose event status is not observed during the study period. A hazard ratio, if reported, compares event rates over time under its model assumptions; it is not itself a median survival time or a response proportion. No sponsor-reported hazard ratios or numerical survival findings are included in this record.

As a general matter, time-to-event analyses can be affected by how events are defined, how follow-up ends, and whether censoring is informative. The registry record does not report enough detail about these elements to assess their handling for the listed secondary outcomes. The general statement that time-to-event tables use sponsor-reported hazard ratios does not supply an estimate when no such result is reported.

Why does over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals can be too narrow. This consideration is relevant to some count-data analyses, but the record does not report an over-dispersion analysis or a count model for the primary outcome. It should not be inferred that such a method was used.

What are the planning illustrations?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that time-to-event illustrations give the total number of events, while other illustrations give participants per arm. These are planning assumptions, not a report of the trial's own design calculations. In particular, a two-arm planning illustration does not change the study's listed single-group design.

As a general statistical distinction, a sample-size calculation asks what enrollment or event total might be needed under stated assumptions. It does not show the power actually achieved after a study, and it cannot stand in for a trial result. The registry record does not report a sample-size justification for the study's design, and the planning assumptions should not be read as observed power.

Finally, the trial's outcome estimates would need to be considered in light of its design and the completeness of reporting. A single treatment group can yield descriptive estimates, but it cannot by itself support a randomized comparison. In this record, the absence of numerical efficacy analyses prevents assessment of the magnitude and precision of any response or survival findings.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists Overall Response Rate as the primary outcome and Progression Free Survival and Overall Survival as secondary outcomes. It lists three outcome measures and zero analyses, but does not report numerical outcome results. The record does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for controlling the chance of false-positive findings across multiple tests. These details are not reported in the registry record.

As a general statistical point, examining several outcomes can increase the chance that at least one appears statistically significant by chance if each is tested separately. Prespecified outcome priorities and multiplicity procedures can help readers distinguish confirmatory findings from exploratory ones. Since no numerical p-values or outcome analyses are reported, the registry record does not permit evaluation of how multiplicity was addressed or whether any result would meet a prespecified testing strategy.

The primary outcome population is identified as ITT. In general, an intention-to-treat analysis aims to retain participants in the groups to which they were assigned, but this is a single-group study and the record does not provide further detail about analysis rules. It does not report missing outcome data, reasons for missing assessments, methods for handling missingness, or sensitivity analyses. Therefore, the potential effect of missing data on the response estimate cannot be assessed.

Likewise, the registry record does not describe the analysis population for the secondary outcomes or give details about censoring and follow-up completeness. It does not report interim analyses, a detailed statistical analysis plan, or sample-size justification. These absent details limit assessment of the planned analysis and the reliability of any efficacy interpretation; no unreported methods should be assumed.

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 5% 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 (4.9%), fever (2.4%), ascites (2.4%), fracture (2.4%), general disorders and administration site conditions - other, specify (2.4%).

The registry lists one treatment group, Combined TAS-102 and TAS-OX. It reports 8 participants affected by serious adverse events among 41 at risk, and 41 participants affected by other adverse events among 41 at risk. The record also reports 37 deaths. These are registry counts and should be read as separate safety summaries, not combined into a new total.

The listed serious adverse-event terms are Thromboembolic event (4.9%), Fever (2.4%), Ascites (2.4%), Fracture (2.4%), General disorders and administration site conditions - Other, specify (2.4%), and Hepatobiliary disorders - Other, specify (2.4%). The registry record does not give further detail about timing, severity grades, attribution, or whether a participant could have more than one event. The listed percentages should not be used to infer unreported counts.

As a general interpretive principle, events occurring during a trial are not automatically caused by the study treatment. A single-group safety summary cannot distinguish treatment effects from the underlying illness, other care, or other causes. Without a control group and further event-level details, these figures describe reported events in the treated group, not comparative risks or proof of causation.

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

The registry record establishes that a single-group Phase 1 and Phase 2 study evaluated combined TAS-102 and oxaliplatin in patients with metastatic colorectal cancer whose cancer had progressed or recurred after FOLFOX chemotherapy. It defines the primary response endpoint with RECIST 1.1 and identifies ITT as the primary outcome population. It also lists Progression Free Survival and Overall Survival as secondary outcomes.

Those details do not establish the size or precision of a treatment effect. The record does not report the numerical Overall Response Rate, the number of responders, a confidence interval, or numerical results for the secondary survival outcomes. The endpoint's metadata describe it as a median in months, which does not match the response-rate definition; the record does not resolve that discrepancy. Accordingly, no numerical efficacy conclusion can be drawn from the posted results described in the registry record.

The record does report serious and other adverse-event counts, along with deaths and several serious-event terms. These observations are useful as descriptions of what was recorded in the treatment group. They do not by themselves show which events were caused by treatment, nor how safety compares with another option. The single-group design offers no concurrent randomized comparison.

In general, a study's statistical interpretation depends on the endpoint definition, analysis population, completeness of outcome data, and uncertainty around estimates, as well as design. Here, the registry supplies some endpoint definitions and safety counts but not the numerical efficacy analyses or several methodological details needed for a fuller evaluation. Absence of a reported result is not evidence that the result was favorable or unfavorable; it means that the registry record does not report it.

Planning illustrations are not trial findings and are not observed power. They cannot fill the gap left by missing outcome estimates. The appropriate scope of interpretation is therefore limited to the listed design, definitions, and reported safety summaries, without claiming that the treatment works or does not work.

13. Why This Trial Matters Statistically

This trial matters statistically because its registry record illustrates the difference between knowing an endpoint's name and having an interpretable endpoint result. The study identifies Overall Response Rate and describes the RECIST 1.1 response criteria, but does not report the response estimate or its uncertainty. Without those values, readers cannot assess the observed frequency of response or its precision.

The record also highlights why endpoint labels must be consistent with endpoint definitions. A response rate is defined through response categories, but the registry labels it as a median measured in months. Since the record does not clarify the mismatch, readers should not silently treat the endpoint as either a rate or a time-to-event measure beyond what its description states.

Design is also central. A single-group trial can describe outcomes among participants receiving an intervention, but it cannot provide a randomized comparison with an alternative treatment. That distinction matters for efficacy and safety alike: a descriptive event count is not a comparative effect, and an outcome observed after treatment is not automatically caused by treatment.

Finally, the record lists planning illustrations alongside a single-group trial description. Their equal-allocation, two-arm assumptions are planning conventions and do not alter the trial design or represent observed power. Clear separation of design, planning, and reported results is essential to prevent statistical calculations from being mistaken for evidence about clinical outcomes.

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.

The main trial-specific limitation in the registry record is that it does not report numerical results for the primary endpoint. Although Overall Response Rate is defined using RECIST 1.1 and an ITT population is named, no response count, rate, or confidence interval is reported. The record also lists zero analyses, so the numerical primary result cannot be evaluated.

Progression Free Survival and Overall Survival are listed as secondary outcomes without numerical findings. The record does not provide event counts, follow-up summaries, survival estimates, hazard ratios, or confidence intervals for these outcomes. It also does not report details needed to judge censoring, outcome completeness, or missing-data handling.

The endpoint metadata are internally difficult to interpret: Overall Response Rate is labeled MEDIAN and months, with a 95% Confidence Interval, although the description defines a response proportion. No explanation of this mismatch is reported. The timeframe is stated as up to 30 days following discontinuation of treatment, but additional assessment scheduling details are not reported.

The single-group design has no concurrent control group, and no randomized comparison is reported. Consequently, the record cannot establish comparative efficacy or safety. The adverse-event summaries do not give further event-level information about timing, severity grades, attribution, or overlap among events. A detailed statistical analysis plan, interim analyses, multiplicity procedures, missing-data methods, and sample-size justification are not reported in the registry record.

The arm description is incomplete, so full dosing and treatment procedures cannot be reconstructed from the record. These limitations restrict interpretation to the design and definitions that are explicitly recorded, plus the reported safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: TAS-OX for Refractory Metastatic Colon Cancer — NCT02848079.
• Registry record last updated 2021-07-20; status last verified 2021-06.
• Results first posted 2021-07-20.
• 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

NCT02848079 is a completed single-group Phase 1 and Phase 2 study sponsored by Yale University. It enrolled 41 participants and evaluated combined TAS-102 and oxaliplatin for metastatic colorectal cancer that had progressed or recurred after FOLFOX chemotherapy. The recorded study start is 2016-10-31, and the primary completion date is 2020-06-02.

The primary outcome is Overall Response Rate, defined using RECIST 1.1, with an ITT population and a timeframe of up to 30 days following discontinuation of treatment. Progression Free Survival and Overall Survival are listed as secondary outcomes. Numerical efficacy results are not reported in the registry record, which lists zero analyses. The record reports 8 participants affected by serious adverse events among 41 at risk, 41 affected by other adverse events among 41 at risk, and 37 deaths.

The registry labels the response endpoint as a median in months, despite defining a response rate. The single-group design does not provide a randomized comparator, and the record does not resolve the endpoint-label mismatch or report the numerical outcomes needed to assess efficacy.