Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer (NCT00055692), a na phase 2 study. The primary outcome is Mean Arterial Enhancement, Per Lesion, as Determined by Dynamic Gadolinium-enhanced Magnetic Resonance Imaging (MRI), Before and Following Bevacizumab Therapy..

2. Clinical Question

3. Trial Design

This completed phase II study evaluated bevacizumab in a single group of participants with unresectable liver cancer. The registry record lists 46 participants as enrolled. It describes the intended disease population as nonmetastatic hepatocellular cancer without invasion of the main portal vein, and also lists adult primary hepatocellular carcinoma, localized unresectable adult primary liver cancer, and recurrent adult primary liver cancer among the conditions. The record lists the National Cancer Institute as sponsor.

The intervention was bevacizumab administered intravenously over 30–90 minutes on day 1, with treatment continuing every 2 weeks if disease had not progressed and toxicity was not unacceptable. This is the treatment schedule described in the record, not a report of how long each participant actually received treatment. Individual exposure, adherence, dose modifications, and discontinuations are not reported in the registry record.

The study is classified as phase II and single-group. Allocation is listed as not applicable, and masking as none. These design features mean there is no randomized comparator or blinded assessment described in the record. The primary endpoint uses repeated imaging: eight consecutive participants enrolled at one site were evaluated with dynamic contrast-enhanced MRI before treatment and at 8 weeks. That imaging subset is distinct from the 46 participants enrolled overall; the record does not explain the subset’s selection or provide a flow of participants through the imaging assessment.

The study is marked completed. The registry record lists a start of 2003-02 and primary completion of 2008-01. It lists six outcome measures, but no analyses. The protocol’s statistical plan, sample-size justification, planned analysis population, and any interim analyses are not reported in the registry record. These omissions limit what can be inferred about whether the posted endpoint description reflects the originally planned analysis or how the imaging subset was handled analytically.

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 Mean Arterial Enhancement, Per Lesion, as Determined by Dynamic Gadolinium-enhanced Magnetic Resonance Imaging (MRI), Before and Following Bevacizumab Therapy., measured over Baseline and 8 weeks after bevacizumab therapy.

The primary endpoint is mean arterial enhancement per lesion, measured in relative MR units by dynamic gadolinium-enhanced magnetic resonance imaging. The record specifies measurements at baseline and 8 weeks after bevacizumab therapy. Dynamic contrast imaging captures changes in the MRI signal associated with contrast moving through tissue; arterial enhancement is an imaging characteristic, rather than a direct count of cancer cells or a direct measure of how long participants live. In general, an imaging measure can help describe changes in tumor appearance or vascular characteristics over time, but its clinical meaning depends on how it is defined, measured, and related to outcomes that matter to patients.

The endpoint is continuous: each measurement can take a range of values, and a group mean describes the average measurement. The record names the standard deviation as the dispersion measure, which would describe how spread out individual values are around the mean. The record does not report the means, standard deviations, or a change estimate, so the direction and magnitude of the imaging findings cannot be assessed from the registry information. It also does not report how lesions were selected, how multiple lesions within a participant were handled, or whether imaging readings were assessed consistently across time.

Because the same participants were imaged before treatment and at 8 weeks, a comparison could in principle focus on within-participant change. In general, such a comparison accounts for the fact that measurements from the same person are related. However, the registry record does not specify the statistical method, and the endpoint description alone does not establish that a particular paired analysis was conducted. Nor does an imaging change, by itself, establish a change in symptoms, disease control, or survival.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Continuous measurements and averages. The primary endpoint is a continuous imaging measurement, reported in relative MR units. In general, a mean is the arithmetic average of observed values and offers a compact description of their central tendency. A standard deviation describes the spread of individual observations around that mean. These summaries answer different questions: the mean characterizes the average level, while the standard deviation indicates how variable the measurements are among the observed participants or lesions. Neither number is reported for the primary endpoint in the registry record, so the measurement’s average level and observed spread cannot be assessed from the registry information.

Repeated measurements. The endpoint description identifies imaging at baseline and at 8 weeks for the same eight participants. In general, repeated measurements from one participant are correlated: a person’s measurements tend to share characteristics that are not shared with measurements from another person. A paired analysis uses the within-person relationship when estimating change, rather than treating the two time points as independent groups. This can be useful because each participant serves as their own reference for the comparison. However, the record does not state which analysis was used, whether the analysis was based on participant-level changes, or how multiple lesions per participant were incorporated. The timing and population description alone do not establish the statistical procedure.

Estimation and uncertainty. In general, an estimated change describes the observed difference between two conditions or time points. A confidence interval gives a range of values compatible with the data and the statistical assumptions used; it conveys precision as well as the estimate’s direction and scale. A narrow interval indicates greater precision than a wide interval, while an interval that includes no change may be compatible with both a decrease and an increase, depending on its limits. These are general concepts, not reported findings for this study: the registry record does not include an estimated endpoint change or a confidence interval. A p-value, if available, would address compatibility with a specified null model under its assumptions, but would not by itself describe the size or clinical relevance of a difference. No primary endpoint p-value is reported in the registry record.

Single-group interpretation. General statistical reasoning distinguishes a within-group change from a treatment effect. A before-and-after comparison describes what happened in the observed group over time; a concurrent comparator can help distinguish that change from background trends and other influences. Because this study is listed as single-group, the registry record does not describe a randomized comparison that would support a direct estimate against a control group. Even if an imaging change were reported, interpreting it as caused by treatment would require assumptions beyond the observed change. The record does not report an analysis designed to address this issue.

Sample-size illustrations. General planning calculations estimate how many participants might be needed under specified assumptions about an effect, variability, significance level, allocation, and statistical model. Such illustrations are not the same as a sample-size justification for the original trial, and they do not measure the probability that this completed trial found a true effect. The record’s planning description characterizes its calculations as illustrations based on an observed effect and specifies assumptions for those calculations. It also distinguishes participants per arm for ordinary outcomes from total events for time-to-event outcomes. These planning conventions do not show that the trial used those assumptions prospectively. The study’s own sample-size justification is not reported in the registry record. The illustrations should therefore be read as hypothetical planning aids, not as observed power or as evidence that the study was adequately or inadequately sized.

Multiplicity and selective interpretation. When a study evaluates multiple endpoints or performs multiple analyses, general statistical practice considers how the number of comparisons affects the chance of observing an apparently unusual result. Methods can adjust for multiplicity or designate a primary endpoint in advance, but the appropriate approach depends on the planned questions and analysis. The registry record lists six outcome measures and zero analyses. It does not report the analysis plan, whether other endpoints were prespecified as secondary, or how multiple comparisons were addressed. Therefore, it is not possible to determine from the record how multiplicity was handled or whether any endpoint was selected for reporting after results were known.

Dispersion and distribution. The endpoint description identifies the standard deviation as the dispersion summary. In general, a mean and standard deviation are most straightforward to interpret when the data are reasonably represented by a symmetric distribution and the observations are appropriately treated as independent at the analysis level. With a small imaging subset, individual observations can have substantial influence on a mean, and a standard deviation may itself be estimated imprecisely. These are general considerations, not claims about the study’s actual data distribution. The registry record does not report the observed values, distributional checks, outlier handling, or an alternative summary. It also does not specify whether the analysis unit was the participant or the lesion, an important distinction when multiple lesions may belong to one participant.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Treatment (Bevacizumab): Baseline", "Treatment (Bevacizumab): 8 Weeks")
n   <- c(8, 8)
m   <- c(37.3, 18.4)
sp  <- c(18.4, 12.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Treatment (Bevacizumab): Baseline  8  37.300  18.400  21.917  52.683
CARM  Treatment (Bevacizumab): 8 Weeks  8  18.400  12.400  8.033  28.767

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and zero analyses. The count of listed measures indicates that the record contains multiple outcomes, but it does not establish which were formally designated primary or secondary beyond the endpoint identified as primary. A count of zero analyses means no analyses are listed in the registry record; it does not show that no statistical work was conducted. The prespecified statistical plan, any hierarchy among outcomes, and any adjustment for multiple testing are not reported in the registry record. Without that information, the effect of multiplicity on interpretation cannot be determined.

Missing-data handling is also not reported. For the imaging endpoint, the record identifies eight consecutive participants at one site as evaluated before treatment and at 8 weeks, but it does not state whether all eight had usable measurements at both times, whether additional participants were considered, or how incomplete scans were handled. It does not describe imputation, exclusion rules, sensitivity analyses, or reasons for missing data. In general, missingness can affect an estimate if participants with observed measurements differ from those without them; the extent and direction of any such effect cannot be assessed without details.

The analysis population is not specified beyond the endpoint description. The record does not say whether the primary analysis included all enrolled participants, only participants who received treatment, or only those with both imaging assessments. The eight-person imaging population should not be conflated with the 46-person enrollment count. No protocol-level analysis population or participant-flow account is reported in the registry record.

12. Safety Results

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

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: hypertension (15.2%), hemorrhage (10.9%), increased bilirubin (10.9%), proteinuria (4.3%), arterial thrombosis (4.3%).

The registry lists a treatment group with 46 participants at risk for serious adverse events and 22 participants recorded as affected. It also lists 46 at risk for other adverse events and 41 affected. These are participant counts, not a report of the total number of individual event episodes; a participant may experience more than one event. The registry separately lists serious adverse event terms with percentages: hypertension, 15.2%; hemorrhage, 10.9%; increased bilirubin, 10.9%; proteinuria, 4.3%; arterial thrombosis, 4.3%; and ascites, 4.3%.

These figures describe the safety observations recorded for the bevacizumab group. With no control group, they do not provide a comparative estimate of how often events would occur without treatment. The figures also do not establish that the treatment caused each event. The registry record does not report deaths. It does not provide, in the registry record recorded for this study, further detail about event timing, severity grading, recurrence, or individual clinical circumstances. The counts and listed terms should therefore be read as descriptive safety information, not as a controlled estimate of treatment-related risk.

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

The registry record establishes that this was a completed phase II, single-group study of bevacizumab in participants with unresectable liver cancer, and that its primary endpoint was mean arterial enhancement per lesion on dynamic gadolinium-enhanced MRI at baseline and 8 weeks. It also describes an imaging assessment in eight consecutive participants at one site and reports safety counts for the overall treatment group. These details identify the study’s design, measured outcome, time point, and some observed safety information.

The record does not report the primary endpoint’s numerical findings. There is no reported mean at either time point, no estimated change, no measure of precision, and no inferential result. Accordingly, the record does not show the direction or size of the imaging change, or how precisely it was estimated. The absence of an analysis in the registry is not evidence that there was no change; it means the result cannot be interpreted from the information recorded.

Even if a within-participant imaging change were available, the single-group design would not by itself separate a treatment-associated change from other changes over time. The endpoint is an imaging measure and does not directly report symptoms, tumor control, or survival. No such conclusions should be drawn from the endpoint description alone. The distinction between the 46 participants enrolled and the eight described for imaging also matters: the imaging result, if reported, would need to be interpreted in relation to that subset and its selection.

The serious and other adverse-event counts provide descriptive information for the treated group, but without a comparator they do not quantify excess risk relative to another treatment or no treatment. Taken together, the registry record supports a description of the trial and its reported safety counts, but it does not provide enough endpoint results or analysis detail to determine the size, precision, or comparative meaning of an imaging effect.

14. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition is only one part of interpreting clinical research. The record specifies a continuous imaging measure, its units, the imaging method, and two assessment times. Those details make the intended measurement understandable. But without the mean values, dispersion, estimated change, or an uncertainty interval, a reader cannot tell what the endpoint showed or how precisely it was measured. A well-described question and a reported answer are not the same thing.

The study also highlights the distinction between the enrolled population and the population contributing to a particular outcome. The record lists 46 participants enrolled overall, while the primary imaging description concerns eight consecutive participants at one site. Recognizing that difference is important when considering how broadly an outcome could apply and when assessing possible selection into the measured subset. The registry record does not explain the subset’s relation to the full enrollment.

Its single-group design is another useful statistical teaching point. Repeated observations can describe change within participants, but they do not supply the counterfactual comparison that a concurrent control group is intended to provide. Statistical significance, even if reported, would not resolve the distinction between observed change and a causal treatment effect on its own. Here, the registry record does not report an endpoint analysis or its result, so that distinction remains especially important.

Finally, the record lists safety counts alongside an imaging endpoint, but they answer different questions. The imaging endpoint concerns a measured characteristic at specified times; adverse-event counts describe reported harms in the treatment group. Neither can substitute for the other. This study therefore offers a useful example of how design, analysis population, endpoint reporting, and safety context all shape what can responsibly be concluded from a clinical trial record.

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 interpreting the efficacy-related endpoint is the lack of numerical results in the registry record. The record names mean arterial enhancement and its measurement times, but gives no observed means, standard deviations, estimated change, confidence interval, or p-value. It is therefore not possible to describe the endpoint’s direction, magnitude, or precision.

The imaging assessment is described for eight consecutive participants at one site, while total enrollment was 46. The record does not explain why only that subset is described, whether all participants had complete imaging, or how participants and lesions were selected. This creates uncertainty about representativeness and about the analysis unit. The record does not state whether results were summarized per participant, per lesion, or with a method accounting for multiple lesions belonging to one participant.

The single-group design provides no concurrent control comparison. A change between baseline and 8 weeks, if available, would be a within-group observation and would not by itself isolate a treatment effect. The record also does not report the statistical analysis plan, missing-data methods, analysis population, multiplicity approach, interim analyses, or sample-size justification. It is consequently not possible to assess whether the posted endpoint and analyses followed a prespecified plan.

For safety, the reported counts are descriptive and lack a comparison group. The registry record does not report deaths, and the listed event terms do not establish causal attribution. These limitations are specific to the design and reporting information available for this study; they do not establish that unreported analyses or information were absent from other records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bevacizumab in Treating Patients With Unresectable Nonmetastatic Liver Cancer — NCT00055692.
• Registry record last updated 2016-02-29; status last verified 2012-12.
• Results first posted 2016-02-29.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00055692 is a completed phase II, single-group study sponsored by the National Cancer Institute. It enrolled 46 participants with unresectable liver cancer and evaluated bevacizumab administered intravenously, with treatment described as continuing every 2 weeks in the absence of progression or unacceptable toxicity.

The primary endpoint was mean arterial enhancement per lesion in relative MR units, assessed by dynamic gadolinium-enhanced MRI at baseline and 8 weeks. The endpoint description concerns eight consecutive participants enrolled at one site. Numerical results and the statistical analysis are not reported in the registry record. The record lists six outcome measures and zero analyses.

For the treatment group, 22 of 46 participants were recorded as affected by serious adverse events and 41 of 46 by other adverse events. The registry lists hypertension, hemorrhage, increased bilirubin, proteinuria, arterial thrombosis, and ascites among the serious adverse event terms. Deaths are not reported in the registry record.