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 A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer. (NCT01227707), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Pathological Complete Response (pCR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01227707 |
| Phase | Phase 2 |
| Condition | Colorectal Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 43 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants had locally advanced primary rectal cancer. The registry lists colorectal cancer as the condition and records enrollment of 43 participants. For the primary endpoint analysis, the stated population was the ITT population, but only participants who underwent surgery and had pathological tumor stage data were included.
Intervention
The study assessed pre-operative bevacizumab, also called Avastin, and capecitabine, also called Xeloda, with standard pelvic radiotherapy. The registry describes 4 courses of bevacizumab at 5 mg/kg intravenously every 2 weeks and 38 days of capecitabine at 825 mg/kg twice daily orally, plus radiation therapy. Surgical and post-surgical treatments were also part of the described treatment pathway.
Comparator
There was no separate control group. The allocation was non-randomized, the model was single-group, and masking was none. The study therefore describes outcomes among participants receiving the treatment strategy; it does not provide a like-for-like randomized comparison against another treatment.
Primary question
The primary endpoint was the percentage of participants with pathological complete response, assessed 6 to 8 weeks following completion of neoadjuvant treatment. The registry defined this response by the absence of viable tumor cells in the surgical specimen, including regional lymph nodes, with pT0 and pN0 at surgery. The numerical endpoint estimate and 95% confidence interval are not reported in the registry record, so the size and precision of the response cannot be assessed from the record.
3. Trial Design
This was a phase 2, open-label study with non-randomized allocation and a single-group model. Enrollment was 43. The study was marked completed. The registry lists a start date of 2005-11 and a primary completion date of 2010-08. Its stated purpose was to assess the effect of bevacizumab and capecitabine combined with pre-operative standard radiotherapy on response rate in people with locally advanced rectal cancer.
The treatment description includes pre-operative therapy, surgery and post-operative treatment. Before surgery, participants were to receive 4 courses of bevacizumab at 5 mg/kg intravenously every 2 weeks and capecitabine at 825 mg/kg twice daily orally for 38 days, together with radiation therapy. Mesorectal excision is listed as an intervention. After surgery, the description includes adjuvant 5-fluorouracil and leucovorin; bevacizumab at 5 mg/kg intravenously every 2 weeks for at least 6 months could also be given at the investigator’s discretion.
Because the study had a single group and no masking, its primary response result would describe outcomes in participants treated under this study strategy. There is no concurrent control group in the registry record from which to estimate a treatment contrast. Differences from outcomes in other settings could reflect differences in participants, treatment delivery, outcome ascertainment or other factors, and cannot be interpreted as a randomized comparison.
The registry lists 13 outcome measures and 1 analysis. It does not report a detailed statistical analysis plan, the method used to calculate the primary confidence interval, or a sample-size justification. Those details are not reported in the registry record. The registration describes the planned treatment and endpoint, but the primary numerical result and confidence interval are also not reported in the registry record.
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 | Bevacizumab (Bv)+Capecitabine/Bv+Leucovorin+5-fluorouracil |
|---|---|
| STARTED | 43 |
| COMPLETED | 19 |
| NOT COMPLETED | 24 |
Reasons for not completing this period:
| Reason | Bevacizumab (Bv)+Capecitabine/Bv+Leucovorin+5-fluorouracil |
|---|---|
| Adverse Event | 10 |
| Progression of disease | 3 |
| Withdrawal by Subject | 1 |
| Patient non-compliance | 3 |
| Medical decision | 6 |
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: ITT population; only participants who underwent surgery and had pathological tumor stage data were included in the analysis.
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: all participants who were included in the trial by signing the informed consent and were assigned to a study patient number.
| Characteristic | Unit | Bv+Capecitabine/Bv+Leucovorin+5-FU |
|---|---|---|
| Participants analysed | 43 | |
| Age, Continuous | years | 61.49 (SD 10.85) |
| Sex: Female, Male: Female | Participants | 18 |
| Sex: Female, Male: Male | Participants | 25 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Pathological Complete Response (pCR), measured over 6 to 8 weeks following completion of neoadjuvant treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with pathological complete response, measured 6 to 8 weeks following completion of neoadjuvant treatment. The registry defined pathological complete response as absence of viable tumor cells in the tumor specimen obtained at surgery, including regional lymph nodes. It specified that participants had to have both pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0). The numerator was the number meeting both criteria; the denominator was the total number of participants with pathological tumor stage data collected.
This endpoint uses the surgical specimen to assess residual tumor after pre-operative treatment. Pathological assessment gives a defined tissue-based outcome, rather than relying only on clinical examination or imaging. The registry says specimens were evaluated by both a central and local pathologist to minimize evaluation bias. That procedure may help address variation in interpretation, but the record does not report agreement between pathologists or how disagreements were resolved.
The endpoint is a proportion, so its interpretation depends on both the number meeting the pCR definition and the denominator used. Although the analysis population is described as ITT, the registry explicitly limits inclusion to participants who underwent surgery and had pathological tumor stage data. The primary estimate and its 95% confidence interval are not reported in the registry record, so neither the observed proportion nor its precision can be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies pathological complete response as the primary outcome, but it does not report the primary response percentage or its stated 95% confidence interval. As a result, the central result cannot be quantified from the registry record. There is no basis in the record for saying how many participants met the pT0 and pN0 criteria, how large the response proportion was, or how precisely it was estimated.
The analysis population also matters. Although the population label includes ITT, the endpoint description says that only participants who underwent surgery and had pathological tumor stage data were included. This means the endpoint denominator is not necessarily the full enrolled group. The record does not report the number who underwent surgery, the number with pathology data, or the reasons any participants might be absent from the endpoint analysis. Those omissions prevent a complete assessment of how the analyzed group relates to enrollment.
This was a single-group, non-randomized study. Even if the primary estimate were available, it would describe the observed response under the study treatment strategy rather than establish a causal difference from another treatment. No randomized comparator is listed. The open-label design also means participants and treating clinicians were not masked, although the registry reports that pathological specimens were assessed by both central and local pathologists to minimize evaluation bias.
The registry lists 13 outcome measures, including clinical stage, surgical procedure, response, new lesions, relapse and disease-free survival outcomes. It does not report a multiplicity procedure or identify a hierarchy for interpreting secondary outcomes. Nor does the record give numerical results for those outcomes in the registry record for this analysis. Accordingly, they cannot be used to reinforce or qualify the primary result.
Safety information is reported for a group titled Bv+Capecitabine/Bv+Leucovorin+5-FU. The group lists 42 participants at risk for serious adverse events, with 8 affected, and 42 at risk for other adverse events, with 39 affected. Six serious adverse event terms are each listed at 2.4%. These entries describe reported events in the registry; they do not by themselves establish that an event was caused by treatment. The number of deaths is not reported in the registry record.
Overall, the registry record allows a description of the design, endpoint definition and some safety counts, but not an assessment of the magnitude or precision of the primary response result. The absence of a control group further limits causal interpretation. Any conclusion about comparative benefit, effectiveness or the balance of benefits and harms would go beyond what these posted data establish.
9. Statistical Methods Explained
The primary outcome is a binary response status at the participant level: a participant either meets the registry’s pathological complete response definition or does not. A percentage expresses the number meeting that definition relative to the endpoint denominator. In this study, the denominator is described as participants with pathological tumor stage data collected, among those who underwent surgery. The registry’s use of the term ITT should therefore be read alongside that specific inclusion description; it does not mean that every enrolled participant necessarily contributed to this endpoint.
What does a confidence interval convey?
A confidence interval describes statistical uncertainty around an estimated quantity. For a proportion, it represents a range of values compatible with the observed data under the assumptions of the interval method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. An interval does not show the probability that the fixed underlying value lies within that particular calculated interval. The registry identifies a 95% confidence interval for the primary endpoint, but its numerical limits and the estimation method are not reported in the registry record. Precision therefore cannot be evaluated from the available endpoint information.
Why does the denominator matter?
For a percentage, the numerator and denominator jointly determine the estimate, and the denominator also affects its precision. The registry defines the pCR numerator using both pT0 and pN0 at surgery and specifies that the total number with pathological tumor stage data is the denominator. Participants without surgery or without the required pathology data are not included according to that description. The record does not state how many participants were excluded from this endpoint denominator or why. Without those details, the extent and potential direction of missing-outcome effects cannot be assessed.
How should a single-group result be read?
A single-group study estimates outcomes in the group receiving the study treatment strategy. It does not directly estimate the difference between that strategy and a control treatment. Random allocation is used in comparative trials to help balance measured and unmeasured participant characteristics between groups; this study had no randomized comparison group. Therefore, an observed response percentage, if reported, would not alone establish that treatment caused the response or that it produces a different outcome from another approach. The open-label design is also relevant to outcomes that may be influenced by knowledge of treatment. Pathology assessment is more directly based on tissue findings, and the registry says both central and local pathologists assessed specimens, but it does not report details of agreement or adjudication.
What does the analysis count tell us?
The registry lists 1 analysis and 13 outcome measures. These counts do not describe the statistical model or explain how the primary endpoint was estimated. No model, test, confidence-interval formula, covariate adjustment, or handling of incomplete observations is specified in the record. These methods are not reported in the registry record. It is therefore not appropriate to infer that a particular standard method was used merely because the endpoint is a percentage.
Multiplicity arises when a study evaluates several outcomes or makes several statistical claims. Repeated testing can increase the chance of at least one apparently unusual result under a null setting unless the analysis plan addresses that issue. The registry lists multiple primary and secondary outcome measures, but does not report a multiplicity adjustment or a prespecified testing hierarchy. The primary endpoint is identified, but the record does not describe whether secondary results were intended to be confirmatory or exploratory. Without those details and the results themselves, interpretation should not treat multiple outcomes as independent confirmation.
What can sample-size planning illustrate?
Sample-size calculations can illustrate how many participants per arm would be needed under stated assumptions to detect a chosen effect with a chosen power and significance level. Such a calculation is a planning exercise, not an observed result and not evidence that a study had a particular probability of finding a real effect. The registry’s design is single-group, whereas the planning description refers to equal allocation between two arms and an effect expressed as a fraction of an observed effect. It says that the illustration was computed from the observed effect, not the trial’s own design. No numerical planning values or observed primary effect are reported in the registry record available for this analysis. The illustration therefore cannot be treated as the trial’s sample-size justification, and a sample-size calculation cannot replace the missing endpoint estimate.
In general, over-dispersion refers to variability greater than assumed by a statistical model. When a model underestimates variability, standard errors may be too small and confidence intervals too narrow. This is a general statistical consideration, not a reported feature of this study: the registry record does not identify a model for the primary proportion or report an over-dispersion assessment.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 40 | 4 | 10.0% | 2.8% to 23.7% | 4.0% to 23.1% | 4.1% to 23.1% |
R code and output
arm <- c("Bv+Capecitabine/Bv+Leucovorin+5-FU")
n <- c(40)
events <- c(4)
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 Bv+Capecitabine/Bv+Leucovorin+5-FU 40 4 10.0 2.8 23.7 4.0 23.1 4.1 23.111. Multiplicity, Missing Data and Analysis Populations
The registry identifies pathological complete response as the primary endpoint and lists 13 outcome measures overall. It does not report a formal multiplicity strategy, such as an adjustment across outcomes, a sequence for testing outcomes, or a distinction between confirmatory and exploratory secondary analyses. The number of analyses listed is 1, but the record does not explain how that count relates to the multiple outcome measures. The methods for controlling the risk of chance findings across outcomes are not reported in the registry record.
Missing data are especially relevant to a pathology-based endpoint because the stated denominator includes participants who underwent surgery and had pathological tumor stage data. The registry does not report the number of enrolled participants with those data, the number without them, or the reasons for missingness. It also does not describe imputation, sensitivity analyses or another approach to incomplete endpoint data. Therefore, the possible influence of unavailable pathology data on the response estimate cannot be assessed.
The record describes the analysis population as ITT while limiting endpoint inclusion to participants with surgery and pathological stage data. Those statements should be read together rather than assuming that all enrolled participants contributed to the primary analysis. How the analysis population was determined in practice, and whether any participants were excluded for other reasons, are not reported in the registry record. The numerical primary result is also not reported, so its denominator, missing-data handling and precision cannot be independently reviewed.
12. 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 |
|---|---|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 8 | 42 | 19.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bv+Capecitabine/Bv+Leucovorin+5-FU | 39 of 42 |
Most frequent serious adverse event terms
| Event term | Organ system | Bv+Capecitabine/Bv+Leucovorin+5-FU |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 42 |
| Miocardic ischemia | Cardiac disorders | 1 of 42 |
| Bowel perforation | Gastrointestinal disorders | 1 of 42 |
| Cardiac ischemia | Cardiac disorders | 1 of 42 |
| Anastomosis dehiscence | Injury, poisoning and procedural complications | 1 of 42 |
| Intestinal occlusion | Gastrointestinal disorders | 1 of 42 |
| Postoperative abscess | Injury, poisoning and procedural complications | 1 of 42 |
| Ipokaliemia | Metabolism and nutrition disorders | 1 of 42 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bv+Capecitabine/Bv+Leucovorin+5-FU |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 18 of 42 |
| Proctalgia | Gastrointestinal disorders | 10 of 42 |
| Nausea | Gastrointestinal disorders | 9 of 42 |
| Hematochezia | Gastrointestinal disorders | 8 of 42 |
| Leukopenia | Blood and lymphatic system disorders | 7 of 42 |
| Rectal tenesmus | Gastrointestinal disorders | 7 of 42 |
| Neutropenia | Blood and lymphatic system disorders | 6 of 42 |
| Abdominal pain | Gastrointestinal disorders | 6 of 42 |
| Asthenia | General disorders | 6 of 42 |
| Hypertension | Vascular disorders | 6 of 42 |
Serious events with the highest arm-level rate: diarrhoea (2.4%), miocardic ischemia (2.4%), bowel perforation (2.4%), cardiac ischemia (2.4%), anastomosis dehiscence (2.4%).
The registry lists a safety group titled Bv+Capecitabine/Bv+Leucovorin+5-FU. It reports 42 participants at risk for serious adverse events, of whom 8 were affected. For other adverse events, it reports 42 at risk and 39 affected. These are separate registry categories; they should not be added together because the record does not say whether participants could appear in both categories.
The listed serious adverse event terms are Diarrhoea, Miocardic ischemia, Bowel perforation, Cardiac ischemia, Anastomosis dehiscence and Intestinal occlusion. Each term is reported at 2.4%. The registry also lists 42 participants at risk, but does not provide event-level counts for each term in the registry record. The percentages should therefore be read as the registry’s reported term-specific values, not converted into counts.
These figures describe events recorded in the safety group. They do not establish that treatment caused the events, and the record does not provide a comparison group for estimating excess risk. The number of deaths is not reported in the registry record. The safety information is therefore descriptive and should be interpreted alongside the study’s single-group design and the limited detail about event ascertainment.
13. What the Result Does, and Does Not, Mean
The registry record establishes that the study was designed to assess pathological complete response after a pre-operative treatment strategy combining bevacizumab, capecitabine and radiotherapy in locally advanced rectal cancer. It provides a specific tissue-based definition of response and states that both central and local pathologists assessed specimens. It also describes surgery and post-operative treatment as part of the study pathway.
However, the primary response percentage and its 95% confidence interval are not reported in the registry record. Without them, the observed frequency of pCR and the uncertainty around that frequency cannot be stated. The enrollment figure alone does not reveal how many participants underwent surgery or contributed pathological data to the endpoint denominator. The record does not report those counts.
The study’s single-group, non-randomized design means that a response result, even if available, would describe outcomes in the treated group rather than measure a randomized treatment effect. It would not establish how the same participants would have fared under a different treatment strategy. Open-label conduct and the absence of a concurrent control also limit comparative interpretation. The central and local pathology assessments are relevant to outcome ascertainment, but the record does not state how their readings compared.
The safety entries give counts of participants affected in the listed categories and term-specific percentages for serious adverse events. They are useful as descriptive registry data, but do not determine causality or comparative safety. Information about deaths, event adjudication and the reasons for missing endpoint data is not reported in the registry record.
Thus, the available record supports a clear description of the study design, endpoint definition and selected safety observations. It does not support a quantitative conclusion about the primary response outcome, a comparison with another treatment, or a causal claim. Those distinctions are important: a defined endpoint and a completed study do not substitute for a reported estimate with its denominator and uncertainty.
14. Why This Trial Matters Statistically
This trial illustrates why reading the endpoint definition and analysis population is as important as recognizing the endpoint name. Pathological complete response is defined using both primary tumor and regional lymph node findings at surgery. The registry further restricts the endpoint denominator to participants who underwent surgery and had pathological stage data. These details determine what the percentage represents and which participants contribute to it.
It also illustrates the difference between an outcome estimate and a treatment effect. A single-group study can describe a response proportion in participants receiving a specified treatment strategy, but it has no concurrent randomized control group for estimating a comparative effect. Non-randomized allocation and open-label conduct are essential context for interpreting any reported result; they cannot be removed by the use of a confidence interval.
Precision is another distinct issue. The registry specifies a 95% confidence interval, but does not report its limits or the primary percentage. Without those values, readers cannot judge the uncertainty of the endpoint estimate. Nor can enrollment alone answer how many participants had evaluable pathology, since that denominator is not reported.
The record also lists multiple outcomes and safety information. This makes it important to distinguish the designated primary endpoint from secondary measures and to know whether multiplicity was addressed. The registry does not describe such a plan. These limitations are not unique to this study, but they are particularly consequential when a registry entry supplies design details without the primary numerical result. The example underscores that definitions, denominators, uncertainty and comparison structure are all needed for sound statistical interpretation.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for statistical interpretation is that the registry record does not report the primary pCR percentage or its 95% confidence interval. Consequently, the response magnitude and precision cannot be assessed. The record also does not report the number of participants who underwent surgery and had pathological stage data, even though this determines the endpoint denominator.
The study was single-group, non-randomized and open-label, with no concurrent control group. Its design therefore does not support a randomized comparison of treatment strategies. The registry says central and local pathologists assessed tumor specimens to minimize evaluation bias, but does not report their agreement, any adjudication process, or further details of outcome assessment.
Although the endpoint population is labeled ITT, the inclusion description limits analysis to participants who underwent surgery and had pathological tumor stage data. The record does not explain how participants without those data were handled, why data may have been unavailable, or whether sensitivity analyses were performed. Missing-data methods are not reported in the registry record.
The registry lists multiple outcomes but does not describe a multiplicity plan, an analysis hierarchy, or which secondary outcomes were intended to be confirmatory. It also does not report the statistical method used for the primary proportion or confidence interval. The number of deaths is not reported in the registry record, and the safety entries do not provide a comparator for causal interpretation.
The described planning illustration is not the trial’s own design justification. The registry does not report a sample-size justification for this single-group trial. These limitations constrain interpretation of efficacy, precision, missingness and safety, even though the study design and endpoint definition are described.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study of Avastin (Bevacizumab) Plus Xeloda (Capecitabine) in Patients With Locally Advanced Rectal Cancer. — NCT01227707.
- Registry record last updated 2015-08-17; status last verified 2015-07.
- Results first posted 2014-08-15.
- 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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19. Record Summary
This phase 2 study was open-label, non-randomized and single-group, with enrollment of 43 participants. It assessed bevacizumab and capecitabine with pre-operative pelvic radiotherapy in locally advanced rectal cancer. The primary endpoint was pathological complete response, assessed 6 to 8 weeks following neoadjuvant treatment and defined by pT0 and pN0 at surgery. Only participants who underwent surgery and had pathological tumor stage data were included in the stated endpoint analysis.
The primary response percentage and 95% confidence interval are not reported in the registry record. The record lists safety data for 42 participants at risk in each of the serious and other adverse event categories, with 8 and 39 affected, respectively. Six serious adverse event terms are listed at 2.4% each. A control group, multiplicity plan, missing-data method and sample-size justification are not reported in the registry record. The available information supports a description of design and measurement, but not a comparative treatment effect.