This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for An Observational Study of First-Line Capecitabine Based Chemotherapy in Participants With Metastatic Colorectal Cancer (NCT01696695), a registered phase not stated study. The primary outcome is Median Progression-free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01696695 |
| Phase | Phase not stated |
| Condition | Colorectal Cancer |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 882 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Newly diagnosed participants with metastatic colorectal cancer. The registry record identifies the primary endpoint population as the ITT Population and reports enrollment of 882 participants.
Intervention
First-line capecitabine-based chemotherapy. Regimens could use capecitabine alone or in combination with other therapies, according to the treating physician’s medical decision before study enrollment.
Comparator
No randomized control group is described. The registry record identifies one group of metastatic colorectal carcinoma participants, and treatment choice was made in clinical practice rather than assigned by the study.
Primary question
What was the median time from the first dose of indicated treatment until disease progression or death, whichever occurred first? The registry record names median progression-free survival as the primary endpoint, but its numerical estimate and confidence interval are not reported in the registry record.
The question concerns outcomes among participants receiving first-line capecitabine-based chemotherapy, not a randomized comparison of one regimen against another. The study aimed to evaluate efficacy and safety during everyday clinical practice. Because the treating physician chose therapy before enrollment, the record does not describe treatment groups formed through random allocation.
The registry lists overall response, clinical benefit, metastasectomy, duration of capecitabine therapy, and dose modification among the secondary outcomes. The listed primary endpoint uses RECIST v1.1 to assess progression. The record describes how progression-free survival was defined and estimated, but does not report its median or 95% confidence interval. Numerical results for the secondary outcomes are also not reported in the registry record.
3. Trial Design
This was an observational study of first-line capecitabine-based chemotherapy in participants with metastatic colorectal cancer. Its stated purpose was to evaluate the efficacy and safety of different capecitabine-based chemotherapies, alone or combined with other therapies, in everyday clinical practice. The registry record reports enrollment of 882 participants and describes a group of newly diagnosed participants receiving first-line treatment.
Treatment was not allocated by randomization. The treating physician selected the therapy before study enrollment, according to the participant’s clinical care. Consequently, the treatment groups cannot be treated as like-for-like randomized groups. Decisions about a regimen may reflect clinical circumstances, and differences between people receiving different regimens could therefore affect comparisons. The registry record does not report a randomized comparison or a statistical adjustment strategy that would address such differences.
The record lists Hoffmann-La Roche as sponsor. The study started in 2011-07, had primary completion in 2014-12, and has status COMPLETED. The listed interventions are capecitabine and chemotherapy. No further detail about treatment-group sizes, regimen-specific outcome estimates, or follow-up by treatment group is reported in the registry record.
Seven outcome measures are recorded, including the primary endpoint and secondary outcomes concerning response, clinical benefit, metastasectomy, treatment duration, and dose modification. The primary endpoint timeframe runs from baseline until progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254. The registry record does not report the study’s sample-size justification, a detailed statistical analysis plan, or numerical efficacy results.
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
| Stage | Metastatic Colorectal Carcinoma (mCRC) Participants |
|---|---|
| STARTED | 882 |
| COMPLETED | 0 |
| NOT COMPLETED | 882 |
Reasons for not completing this period:
| Reason | Metastatic Colorectal Carcinoma (mCRC) Participants |
|---|---|
| Disease progression | 373 |
| Death | 29 |
| Adverse Event | 74 |
| Withdrawal by Subject | 92 |
| Lost to Follow-up | 48 |
| Other | 74 |
| Major Protocol Violation | 192 |
Analysis population for the primary outcome, as defined in the registry: ITT Population
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: Intent to treat (ITT) population included all enrolled participants who provided evaluable data for efficacy variables.
| Characteristic | Unit | mCRC Participants |
|---|---|---|
| Participants analysed | 690 | |
| Age, Continuous | years | 64.9 (SD 10.51) |
| Sex: Female, Male: Female | Participants | 289 |
| Sex: Female, Male: Male | Participants | 401 |
6. Primary Endpoint
The registry lists the primary outcome as Median Progression-free Survival (PFS), measured over Baseline until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurred first, evaluated up to Day 1254.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is median progression-free survival (PFS), measured in days. PFS is defined as the time from the first dose of indicated treatment to disease progression or death, whichever occurred first. The record states that progression was assessed using RECIST v1.1. For participants who did not progress or die while being followed, the record specifies censoring at the date of the last visit.
In general, a time-to-event endpoint incorporates both how long participants are followed and whether the event of interest is observed. A median PFS estimate describes the time by which an estimated half of the relevant population has experienced progression or death, subject to the endpoint’s definitions and censoring. It is commonly used when the outcome is a duration and participants may have different follow-up times. A confidence interval communicates uncertainty around the estimated median; it does not guarantee that the true value falls within the interval.
The record says median PFS was estimated using the Kaplan-Meier method. It also specifies that participants without post-baseline tumor assessments were conservatively censored on the date of first study medication, with PFS assigned a value of 1 day. Although the endpoint definition and estimation method are described, the median and its 95% confidence interval are not reported in the registry record. Thus, the endpoint’s numerical result and precision cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies median PFS as the primary endpoint and describes its definition, assessment approach, and estimation method. It does not report the median PFS value or its 95% confidence interval. Without those numerical results, the magnitude of the observed time-to-event outcome and the precision of its estimate cannot be evaluated. No conclusion about the size or direction of an observed PFS result can be drawn from the endpoint description alone.
The record also does not report numerical results for the listed secondary outcomes. Those outcomes include overall response and clinical benefit assessed using RECIST v1.1, metastasectomy, duration of capecitabine therapy, and dose modification. Their inclusion describes what the study intended to assess; it does not establish what was observed.
The observational design is important when interpreting any comparisons between treatment regimens. Physicians chose therapy before enrollment, and allocation was not randomized. In general, treatment groups formed this way may differ in clinical characteristics that also relate to outcomes. A difference between groups, if reported, would not by itself isolate the effect of treatment. The registry record does not report a statistical adjustment strategy or a randomized comparison that could resolve this concern.
The record reports enrollment of 882 participants, but it does not give a numerical PFS estimate, a hazard ratio, or an analysis result for a treatment comparison. The number of analyses recorded is 0. Numerical sponsor-reported hazard ratios are not reported in the registry record. The record therefore supports a description of the study design and endpoint methods, but not a quantitative statement about the primary outcome.
Safety information is reported separately from the efficacy endpoint. The record lists 55 participants affected by serious adverse events and 140 affected by other adverse events among 882 participants at risk, along with percentages for selected serious adverse event terms. These figures describe reported adverse events in the study population; they do not establish that a particular treatment caused an event. The registry record does not report deaths in the safety summary.
Any planning calculations based on an observed effect should be read as illustrations rather than as evidence about the trial’s design or the certainty of its findings. They are not observed power. The record does not report the study’s own sample-size justification. With the primary numerical result and its uncertainty absent, the findings’ statistical precision cannot be assessed from this registry record.
9. Statistical Methods Explained
How should median progression-free survival be understood?
PFS is a time-to-event outcome: the measured duration ends at progression or death, whichever occurs first. In general, this type of endpoint is useful when participants may be followed for different lengths of time and some have not experienced the event by their last observation. The endpoint must be interpreted using the stated event definition, assessment schedule, and censoring rules.
The record defines progression using RECIST v1.1. It describes progression as an increase of at least 20 percent in the sum of diameters of target lesions compared with the smallest sum observed on study, together with an absolute increase of at least 5 millimeter; progression of existing non-target lesions; or the presence of new lesions. These criteria specify how tumor changes qualify as progression for this endpoint.
What does the Kaplan-Meier method do?
The record states that median PFS was estimated by the Kaplan-Meier method. In general, this method estimates the probability of remaining free of the event over time while accounting for participants whose event status is not observed through the end of follow-up. It uses event times and censoring times rather than treating every participant as though follow-up were identical. The median is identified from the estimated survival curve at the point where the estimated event-free probability reaches one half, if the curve reaches that point.
A 95% confidence interval is a measure of statistical uncertainty around an estimate. In general, an interval that spans a broad range reflects less precision than a narrower interval. The registry record names a 95% confidence interval as the dispersion measure for median PFS, but does not report its endpoints or the median estimate itself. The numerical precision therefore cannot be judged.
What does censoring mean in this record?
Censoring means that the exact time of progression or death is not observed for a participant during the available follow-up. The record says that participants who did not progress or die while being followed were censored at the date of their last visit. Their follow-up contributes information up to that point, but their later event status is unknown in the record.
For participants without post-baseline tumor assessments, the record specifies conservative censoring on the date of first study medication and assigns PFS a value of 1 day. This is a stated rule for handling that situation, not evidence that progression was observed on that day. The record does not report how many participants were handled this way.
Why does the observational design matter?
In general, randomization helps balance both known and unknown prognostic factors across treatment groups. Here, treatment was selected by the treating physician before enrollment, and the study was observational. If outcomes for different regimens are compared, differences may reflect who received each regimen as well as treatment itself. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjustment method. It also does not describe a randomized allocation or a like-for-like control comparison.
What can planning calculations establish?
In general, sample-size planning calculations use assumptions about the effect to detect, the significance level, allocation, and a statistical model. An illustration based on an observed effect is not the trial’s original sample-size justification and does not show the trial’s observed power. The record describes planning assumptions for such illustrations, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also distinguishes total event counts for time-to-event planning from participants per arm for other outcomes. No numerical planning outputs or study-specific sample-size justification are reported in the registry record.
The registry record reports 0 analyses. It does not report numerical sponsor hazard ratios or other efficacy analysis results. Accordingly, the methods described in the record explain how the primary endpoint was defined and estimated, but the absence of numerical results prevents interpretation of the estimated effect or its precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists seven outcome measures and names median PFS as the primary endpoint. It also lists secondary outcomes concerning overall response, clinical benefit, metastasectomy, duration of capecitabine therapy, and dose modification. The record does not report a multiplicity strategy, such as a rule for controlling the chance of false-positive findings across several outcome tests. It also does not report a detailed statistical analysis plan or a set of numerical analysis results. The recorded number of analyses is 0.
In general, when several outcomes or comparisons are examined, interpreting each result as though it were the only test can overstate the evidence from nominal statistical significance. A prespecified testing hierarchy or other multiplicity approach can clarify how findings should be judged. No such approach is reported in the registry record, so it is not possible to determine how multiple outcomes were intended to affect inferential conclusions.
The endpoint description does provide specific rules for censoring: participants without progression or death during follow-up were censored at the last visit, while those without post-baseline tumor assessments were conservatively censored at the date of first study medication and assigned PFS of 1 day. However, the record does not report the amount of missing outcome information, the number of participants affected by these rules, or sensitivity analyses addressing missing assessments. Those details would help readers understand how missing observations may affect the endpoint estimate.
The primary population is identified as the ITT Population, but the registry record does not further explain its analysis-population procedures. The record also does not report a method for handling missing values in the secondary outcomes. These omissions limit assessment of how complete data were and how analysis decisions may have influenced results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| mCRC Participants | 55 | 882 | 6.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| mCRC Participants | 140 of 882 |
Most frequent serious adverse event terms
| Event term | Organ system | mCRC Participants |
|---|---|---|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 4 of 882 |
| Neutropenia | Blood and lymphatic system disorders | 3 of 882 |
| Heart failure | Cardiac disorders | 3 of 882 |
| Diarrhoea | Gastrointestinal disorders | 3 of 882 |
| Atrial fibrillation | Cardiac disorders | 2 of 882 |
| Ileus | Gastrointestinal disorders | 2 of 882 |
| Jaundice | Hepatobiliary disorders | 2 of 882 |
| Dehydration | Metabolism and nutrition disorders | 2 of 882 |
| Palmar-plantar erythrodysaesthesia syndroma | Skin and subcutaneous tissue disorders | 2 of 882 |
| Anemia | Blood and lymphatic system disorders | 1 of 882 |
Most frequent non-serious adverse event terms
| Event term | Organ system | mCRC Participants |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 98 of 882 |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | 51 of 882 |
Serious events with the highest arm-level rate: pulmonary embolism (0.5%), neutropenia (0.3%), heart failure (0.3%), diarrhoea (0.3%), atrial fibrillation (0.2%).
The safety summary reports 882 participants at risk for serious adverse events and 882 at risk for other adverse events. It reports 55 participants affected by serious adverse events and 140 affected by other adverse events. These are separate reported categories; the registry record does not specify whether participants could appear in both.
The listed serious adverse event terms and percentages are pulmonary embolism, 0.5%; neutropenia, 0.3%; heart failure, 0.3%; diarrhoea, 0.3%; atrial fibrillation, 0.2%; and ileus, 0.2%. These percentages describe the registry’s reported figures for selected terms. They should not be read as a comparison between treatment regimens or as proof that treatment caused the events. The record does not report a comparator group allocated through randomization.
The deaths field is not populated with a numerical result, so deaths are not reported in the registry record. The record also does not provide further detail about event timing, severity beyond the serious-event classification, or causal assessment. In general, safety summaries describe events observed and recorded during a study; interpretation depends on definitions, follow-up, exposure, and how events were attributed. These details should not be inferred when they are not reported.
12. What the Result Does, and Does Not, Mean
The record establishes that an observational study evaluated first-line capecitabine-based chemotherapy in newly diagnosed participants with metastatic colorectal cancer during everyday clinical practice. It specifies median PFS as the primary endpoint, defines progression and death as events, and describes use of RECIST v1.1 and the Kaplan-Meier method. It also records enrollment of 882 participants and provides a brief safety summary.
Those design and methods details do not substitute for outcome estimates. The median PFS and its 95% confidence interval are not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported. As a result, readers cannot use this record to quantify the primary outcome, judge its precision, or evaluate the secondary outcomes.
The study’s observational structure also limits causal interpretation. Treatment was selected by the treating physician before enrollment, not randomly assigned. In general, comparisons between treatment regimens in such a study can be affected by differences among the participants receiving each regimen. The registry record does not report an adjustment approach or a randomized comparison that would support a causal treatment contrast.
The serious and other adverse event counts and selected serious-event percentages describe reported safety observations. They do not establish that a therapy caused an event, and the record does not report a numerical death result. The figures should be interpreted as descriptive rather than as evidence from a randomized safety comparison.
Overall, the registry record allows a reader to understand the study question, endpoint definition, and broad design. It does not report the numerical efficacy results needed to estimate the observed PFS outcome or assess statistical uncertainty. The absence of those results means that no conclusion about the magnitude of an observed treatment effect is supported by this record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of how a real-world observational question differs from a randomized efficacy comparison. The treating physician chose the first-line capecitabine-based therapy before enrollment. That design reflects the study’s stated interest in everyday clinical practice, while also meaning that treatment groups are not made comparable by random allocation.
The primary endpoint is a time-to-event measure, and the registry record identifies relevant components of its analysis: a RECIST v1.1 progression definition, rules for censoring, and Kaplan-Meier estimation of median PFS. These details matter because the result depends not only on when progression or death occurs, but also on how assessment and follow-up information are handled.
The record also illustrates the distinction between describing methods and reporting results. It names a primary outcome and several secondary outcomes, but does not report the numerical PFS estimate, its confidence interval, or results for the secondary outcomes. Without those values, statistical precision and the size of any observed outcome cannot be assessed. A completed study status does not itself provide the missing estimates.
Finally, the safety figures require descriptive interpretation. They record affected participants and selected serious-event terms, but do not establish causation or provide a randomized comparison. The registry record is therefore useful for understanding the intended clinical setting and statistical definitions, while its missing numerical efficacy results sharply limit what can be concluded about 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 most important limitation for statistical interpretation is that the registry record does not report the numerical primary endpoint result. Although it identifies median PFS, a 95% confidence interval, and Kaplan-Meier estimation, the median and interval are absent. Numerical results for the secondary outcomes are also not reported. This prevents assessment of outcome magnitude and precision.
The study was observational, and the treating physician chose therapy before enrollment. The record therefore does not describe randomized treatment groups or a like-for-like control comparison. The registry record does not report an adjustment strategy for differences between participants receiving different regimens, so any regimen comparison would require caution.
The record does not report a detailed statistical analysis plan, the study’s sample-size justification, a multiplicity strategy, or numerical analysis results. It reports 0 analyses. It also does not report the number of participants with missing post-baseline tumor assessments, the number censored under each rule, or sensitivity analyses for missing assessments. Those omissions make it difficult to evaluate the robustness of the endpoint analysis.
The safety summary includes counts and selected event percentages, but the record does not report a numerical death result or further detail about event timing and attribution. The listed adverse events should therefore be read descriptively, not as proof of treatment causation. Finally, the record’s stated follow-up timeframe extends through Day 1254, but the numerical PFS result needed to understand the observed outcome is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Observational Study of First-Line Capecitabine Based Chemotherapy in Participants With Metastatic Colorectal Cancer — NCT01696695.
- Registry record last updated 2017-03-23; status last verified 2017-02.
- Results first posted 2016-11-09.
- 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.
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18. Record Summary
NCT01696695 is an observational study of first-line capecitabine-based chemotherapy in newly diagnosed participants with metastatic colorectal cancer. The registry record reports enrollment of 882 participants, sponsor Hoffmann-La Roche, study start in 2011-07, primary completion in 2014-12, and status COMPLETED. Treatment was selected by the treating physician before enrollment.
The primary endpoint was median PFS in the ITT Population, assessed using RECIST v1.1 and estimated by Kaplan-Meier. The record defines progression and describes censoring, but does not report the median PFS estimate or its 95% confidence interval. Numerical results for the secondary outcomes are not reported in the registry record.
The safety summary reports 55 participants affected by serious adverse events and 140 affected by other adverse events among 882 at risk, with selected serious-event percentages. The registry record does not report a numerical result for deaths. Its observational design and absent numerical efficacy results limit causal and quantitative interpretation.