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) and Transarterial Chemoembolisation (TACE) Treatment in Patients With Liver Cancer (NCT00576199), a na phase 2 study. The primary outcome is Progression-free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00576199 |
| Phase | Phase 2 |
| Condition | Liver Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Patients with localized unresectable hepatocellular carcinoma. The primary outcome population is described as participants who received study medication.
Intervention
Bevacizumab 5 mg/kg intravenously, administered every 2 weeks and 24–48 hours before TACE, with TACE scheduled in four sessions at 8–10 week intervals. Continuation depended on disease progression, unmanageable toxicity, and investigator discretion as described in the registry record.
Comparator
There was no separate comparator group. This was a single-arm study, so the treatment combination was not compared with a control arm within the trial.
Primary question
What was the median progression-free survival, measured from the first study-drug administration to documented disease progression or death, whichever occurred first?
The study examined bevacizumab given in relation to TACE in patients with localized unresectable liver cancer. Its primary question is about the time until a progression-free survival event, not a comparison between two assigned treatments. The registry record identifies the primary outcome as median progression-free survival and specifies a 95% confidence interval as its measure of uncertainty. However, the numerical median and confidence interval are not reported in the registry record.
The record also lists outcomes concerning objective response, time to progression, overall survival, best overall response, and tumor necrosis. Their presence indicates areas of assessment, but their numerical results are not reported in the registry record. Without a control group, the trial can describe outcomes among participants receiving the study regimen, but it cannot estimate a randomized treatment contrast against another regimen or usual care.
3. Trial Design
This was a Phase II, single-arm, open-label, multicentre study sponsored by Hoffmann-La Roche. The registry record describes 30 enrolled participants and marks the study as completed. The study began in 2008-02, and primary completion was recorded as 2011-05. These registry dates describe the study record; they do not supply the missing numerical outcome results.
Participants received bevacizumab with TACE. Bevacizumab was administered intravenously at 5 mg/kg every 2 weeks and within 24–48 hours before a TACE session. TACE was scheduled for four sessions at intervals of 8–10 weeks. The brief summary also describes TACE intervals of 8 or 10 weeks and notes that continuation depended on investigator discretion. Treatment with bevacizumab was described as continuing until disease progression or unmanageable toxicity.
Because the study had a single treatment group and no masking, participants and investigators were not blinded to the assigned regimen. There was no randomized allocation between treatment arms. As a result, the design can provide descriptive information about outcomes observed during treatment, but it does not separate treatment effects from other influences that could affect outcomes. The registry record does not report a control group, a comparative treatment estimate, or a statistical plan for adjusting comparisons.
The primary outcome was progression-free survival in an intent-to-treat population defined in the registry record as all participants who received study medication. Its stated timeframe was baseline to the end of the study, up to 3 years, 3 months. The numerical outcome estimate is not reported in the registry record, so the design and endpoint can be described but the observed median cannot be interpreted.
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.
Before assignment: The Participant Flow data are discontinuations from bevacizumab treatment. Data for discontinuations from the study are not available.
Overall Study
| Stage | Bevacizumab 5 mg/kg |
|---|---|
| STARTED | 30 |
| COMPLETED | 0 |
| NOT COMPLETED | 30 |
Reasons for not completing this period:
| Reason | Bevacizumab 5 mg/kg |
|---|---|
| Adverse Event | 12 |
| Insufficient Therapeutic Response | 14 |
| Refused Treatment | 2 |
| Reason Unspecified | 2 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: All participants who received study medication.
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 population: All participants who received study medication.
| Characteristic | Unit | Bevacizumab 5 mg/kg |
|---|---|---|
| Participants analysed | 30 | |
| Age, Continuous | years | 62.8 (SD 10.43) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 26 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival, measured over Baseline to the end of the study (up to 3 years, 3 months).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from the first administration of study drug until the first documented disease progression or death, whichever occurs first. It is a time-to-event outcome: each participant’s follow-up contributes information about how long the participant remained without either event, subject to the follow-up and event-recording procedures used in the study.
The registry definition describes progressive disease as at least a 20% increase in the sum of the longest diameters of target lesions, using the smallest recorded sum since treatment began as the reference, or unequivocal progression of existing non-target lesions. It also describes how target lesions were to be selected and measured. The endpoint therefore combines a tumor-progression criterion with death, rather than measuring tumor size alone.
In general, a median time-to-event outcome gives the time by which half of the event-time distribution has occurred, as estimated from the observed follow-up. A 95% confidence interval conveys uncertainty around that estimate under the statistical method’s assumptions. The registry record specifies a median and 95% confidence interval for this endpoint, but does not report their numerical values. The endpoint is used to describe time without progression or death; it does not, by itself, establish that a treatment caused a particular outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies progression-free survival as the primary outcome and describes its event definition and intended summary. It does not report a numerical median, a 95% confidence interval, or a hazard ratio for that outcome. Consequently, the magnitude and precision of the observed progression-free survival cannot be assessed from the registry record. A definition of an endpoint is not a result, and the planned form of reporting does not reveal the observed value.
The study’s single-arm design is central to interpretation. Outcomes among participants treated with bevacizumab and TACE would describe what was observed in that group, but there is no concurrently assigned control group against which to estimate a randomized difference. Changes over time or clinical outcomes could reflect factors other than the treatment combination. The record therefore does not support a controlled causal comparison, and no such comparison should be inferred from the endpoint definition or treatment schedule.
The record lists 6 outcome measures and 0 analysis entries. It names response, progression, survival, and tumor-necrosis outcomes, but their numerical results are not reported in the registry record. The absence of analysis entries does not establish that no analyses were performed; it means that analysis results are not recorded in the entries described. The sponsor’s statistical analyses, if any, are not reported in the registry record.
Precision cannot be judged without the outcome estimate and its confidence interval. In general, a wider interval indicates greater uncertainty about the value compatible with the data under the method used, while a narrower interval indicates greater precision. Neither direction can be assessed because the interval endpoints are absent. Likewise, no conclusion about statistical significance can be drawn without a reported estimate and applicable inferential result.
The registry describes the primary analysis population as all participants who received study medication. It does not provide details about how incomplete follow-up, censoring, or missing outcome assessments were handled. Those details matter for time-to-event interpretation because participants may have differing amounts of observed follow-up. The record also does not report an interim analysis plan, sample-size justification, or a prespecified multiplicity procedure.
The posted safety entries describe serious and other adverse-event counts and list serious-event terms with percentages. These observations provide a descriptive safety record, not a randomized safety comparison. Events may occur in the same participant, and the record does not give enough detail to infer comparative risks or attribute every reported event to a particular treatment component. The results should therefore be read as registry descriptions of a treated group, with the limits imposed by the missing outcome estimates and the absence of a control arm.
9. Statistical Methods Explained
Progression-free survival is a time-to-event endpoint. For each participant, the relevant time begins at the first administration of study drug and ends at the first documented progression or death, whichever occurs first, according to the registry definition. This endpoint combines two types of event into a single outcome. A participant who experiences either event has reached the endpoint even if the other event has not occurred.
What does a median time-to-event estimate mean?
In general, the median is a summary of the distribution of event times. It represents the estimated point in time by which half of the event-time distribution has experienced the event. Unlike an arithmetic average, a median does not require adding all observed times and dividing by the number of observations. For time-to-event data, estimation can account for participants whose event has not been observed by the end of their follow-up, subject to the method and assumptions used.
The registry record specifies the median as the primary outcome parameter and a 95% confidence interval as its dispersion measure. It does not report the numerical median or the interval endpoints. The reader therefore cannot assess either the estimated time or how precisely it was estimated. Reporting the intended summary and its uncertainty measure is not a substitute for reporting the values.
Why is censoring relevant?
In general, a participant’s event time may be incompletely observed. For example, follow-up can end before an event is documented. Time-to-event methods can use the participant’s observed follow-up without treating the unobserved time as though it were a known event time. This is commonly handled through censoring, but the specific censoring rules and follow-up procedures for this study are not reported in the registry record.
Censoring assumptions matter because the validity of time-to-event estimates depends on how the end of observed follow-up relates to the chance of experiencing the event. The registry record does not describe the amount or pattern of censoring, how participants lost to follow-up were treated, or whether sensitivity analyses were conducted. These omissions limit the ability to evaluate how missing follow-up could affect the endpoint.
How should the confidence interval be read?
In general, a confidence interval expresses statistical uncertainty around an estimate under a specified method and its assumptions. It is not a range containing every individual participant’s outcome, and it does not describe the distribution of all event times. The width of an interval is informative about precision: a wider interval indicates less precise estimation than a narrower interval. The record specifies a 95% confidence interval but gives no numerical bounds, so precision cannot be evaluated for this result.
A confidence interval also does not correct a design limitation. Even a precise estimate from a single-arm study would describe the treated group rather than establish what would have happened under a different treatment. An interval around a single-group median does not create a comparison group or remove possible confounding and selection effects.
What does the design imply for comparisons?
This study is described as single-group, open-label, and without allocation to a comparator arm. In general, randomization helps balance measured and unmeasured baseline factors between treatment groups, on average, and a concurrent control group provides a direct basis for a treatment contrast. Neither feature is present in this design. Consequently, the registry record can support a description of outcomes observed in the treated group, but does not provide a randomized estimate of the difference between the regimen and another option.
The study’s intervention combined bevacizumab and TACE. A single-group outcome cannot isolate the contribution of either component from the other, or distinguish their effects from background factors. This is a design limitation, not a defect that can be repaired by interpreting a median or confidence interval more strongly.
How should planning calculations be distinguished from observed results?
In general, a sample-size calculation is a planning exercise based on assumptions about an effect, variability, allocation, significance level, and desired power. It is not an observed trial outcome and does not tell readers how much power the completed study actually had. The registry record does not report the original sample-size justification. A planning illustration described for the posted analysis uses an observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation; time-to-event planning is described in terms of total events. These assumptions do not provide the missing primary endpoint result, and the illustration should not be treated as evidence of observed treatment effect.
In general, a hazard ratio compares event rates over follow-up between groups under a time-to-event model. It is a relative measure, not a median survival time, and its interpretation depends on the comparison, model assumptions, and analysis population. The registry record does not report a sponsor hazard ratio for this single-group study. No hazard-ratio conclusion can therefore be drawn from the available registry entries.
Finally, the registry record identifies an intent-to-treat population for the primary outcome as participants who received study medication. The exact analysis implementation, handling of missing measurements, and detailed statistical methods are not reported in the registry record. A population label and endpoint definition clarify what was intended to be summarized, but do not establish how every analysis decision was made.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 6 outcome measures. Progression-free survival is identified as the primary outcome; the other listed outcomes concern objective response, time to progression, overall survival, best overall response, and tumor necrosis. The numerical results for these outcomes are not reported in the registry record. The record also lists 0 analysis entries, so it does not provide analysis-specific estimates or inferential results for interpreting the outcomes.
When a study examines several outcomes or performs multiple statistical tests, the chance of at least one apparently unusual result can increase. In general, a prespecified multiplicity strategy can clarify which tests are confirmatory and how inference is adjusted or prioritized. The registry record does not report a multiplicity procedure, a testing hierarchy, or how results across the outcome measures were handled. No claim about adjustment or prioritization can be made.
The primary endpoint population is described as all participants who received study medication. The registry record does not give details about participant-level missingness, incomplete follow-up, censoring rules, or imputation. For a time-to-event endpoint, those details affect how observed follow-up contributes to the estimate. It is therefore not possible to assess the impact of missing data or to determine whether any sensitivity analyses were used.
The record does not report an interim analysis plan, nor does it report a sample-size justification. The study’s completed status does not fill in those missing methodological details. These omissions concern what can be evaluated from the registry record; they do not establish what procedures may or may not have been used outside the record.
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 |
|---|---|---|---|
| Bevacizumab 5 mg/kg | 17 | 30 | 56.7% |
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 |
|---|---|
| Bevacizumab 5 mg/kg | 17 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Bevacizumab 5 mg/kg |
|---|---|---|
| Abdominal pain upper | Gastrointestinal disorders | 2 of 30 |
| Liver abscess | Infections and infestations | 2 of 30 |
| Chest discomfort | General disorders | 2 of 30 |
| Pyrexia | General disorders | 2 of 30 |
| Liver carcinoma ruptured | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 30 |
| Hypertension | Vascular disorders | 2 of 30 |
| Abdominal pain | Gastrointestinal disorders | 1 of 30 |
| Duodenal ulcer | Gastrointestinal disorders | 1 of 30 |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | 1 of 30 |
| Haemorrhoids | Gastrointestinal disorders | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bevacizumab 5 mg/kg |
|---|---|---|
| Hypertension | Vascular disorders | 10 of 30 |
| Thrombocytopenia | Blood and lymphatic system disorders | 4 of 30 |
| Epistaxis | Vascular disorders | 2 of 30 |
| Gingival bleeding | Gastrointestinal disorders | 2 of 30 |
| Injection site haematoma | Injury, poisoning and procedural complications | 2 of 30 |
| Puncture site haemorrhage | Injury, poisoning and procedural complications | 2 of 30 |
| Liver abscess | Hepatobiliary disorders | 2 of 30 |
| Hyperbilirubinaemia | Blood and lymphatic system disorders | 2 of 30 |
| Wound complication | Injury, poisoning and procedural complications | 2 of 30 |
| Haemoptysis | Vascular disorders | 1 of 30 |
Serious events with the highest arm-level rate: abdominal pain upper (6.7%), liver abscess (6.7%), chest discomfort (6.7%), pyrexia (6.7%), liver carcinoma ruptured (6.7%).
The safety record describes a bevacizumab 5 mg/kg group with 30 participants at risk for serious adverse events and 17 participants affected. It also records 30 participants at risk for other adverse events and 17 affected. The registry record does not report deaths for this entry.
The listed serious adverse-event terms are abdominal pain upper, liver abscess, chest discomfort, pyrexia, liver carcinoma ruptured, and hypertension. Each term is reported as 6.7%. These percentages describe the entries as recorded; they do not establish that the events were caused by the study treatment. The record does not provide a comparison group for estimating whether event occurrence differed from another treatment or background risk.
Adverse-event terms are not necessarily mutually exclusive: one participant may experience more than one event, and event categories may overlap. Therefore, the listed term percentages should not be added together to produce an overall proportion. The record also does not supply detail about event timing, severity beyond the serious-event classification, duration, or attribution. These figures are descriptive registry information and should be interpreted within those limits.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed, open-label, single-arm Phase II study assessed bevacizumab administered around TACE in patients with localized unresectable hepatocellular carcinoma. It specifies the primary endpoint, its event definition, and the intended summary as median progression-free survival with a 95% confidence interval. It also describes the treatment schedule and lists other outcome domains and safety entries.
What the record does not establish is the numerical primary outcome. The median and confidence interval are not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported in the registry record. Without those estimates, the direction, magnitude, and precision of the observed progression-free survival cannot be described. No statistical significance conclusion can be drawn from the endpoint definition alone.
The design also limits the scope of any conclusion. With no comparator group, there is no within-trial randomized contrast for estimating how outcomes differed under another treatment. Observed outcomes in the treated group cannot by themselves show what would have occurred in the absence of the regimen. Because bevacizumab and TACE were combined, the design cannot isolate the contribution of either component.
In general, a single-arm study can describe treatment delivery and outcomes among participants enrolled, and can document events during follow-up. It is not a substitute for a controlled comparison when the question is whether one treatment strategy changes outcomes relative to another. Likewise, an adverse-event percentage is descriptive and does not establish causation or comparative safety.
The most defensible reading is therefore limited: the registry record describes the study’s design, treatment, endpoint definitions, and some adverse-event observations, but does not report the numerical efficacy results needed to interpret the primary or secondary outcomes. No claim that the treatment works or does not work follows from the available record.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between defining an endpoint and reporting an estimate. The registry record gives a detailed progression-free survival definition, including the time origin, event components, and tumor-progression criteria. It also specifies the median and 95% confidence interval as the intended summary. Yet the numerical estimate and interval are not reported in the registry record. Endpoint detail alone cannot answer the clinical question about observed time without progression or death.
The design makes the comparison question equally important. A single-arm study can document outcomes among participants who received a regimen, but it has no randomized comparator for separating treatment-associated outcomes from other influences. Since bevacizumab and TACE were administered together, the study also cannot separate the effect of one component from the other. These limits apply even if numerical outcomes are available.
The record also illustrates why safety counts require context. Affected-participant counts and event-term percentages describe reported observations, while a comparator and detailed event attribution would be needed for a comparative interpretation. The listed terms may overlap, so their percentages are not a total measure of participants affected.
Finally, the distinction between a statistical plan, an analysis result, and a planning calculation matters. The registry record lists 0 analysis entries and does not report a sample-size justification or multiplicity strategy. A planning illustration based on assumptions is not an observed result and cannot replace the missing outcome estimates. For readers assessing evidence, these distinctions help prevent a study’s endpoint definitions or design details from being mistaken for proof of an outcome.
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 limitation for interpreting efficacy is that numerical results for the primary endpoint are not reported in the registry record. Although progression-free survival is defined and a median with a 95% confidence interval is specified, neither the estimate nor the interval endpoints are available. The numerical results for the listed secondary outcomes are also not reported in the registry record.
The study is single-arm and open-label, with no comparator group. It therefore cannot provide a randomized comparison, and any descriptive outcome among treated participants cannot be interpreted as a treatment effect relative to another strategy. Since bevacizumab was combined with TACE, the record also cannot isolate the association of either intervention component with an observed outcome.
Further methodological details are not reported in the registry record. These include the original sample-size justification, interim analysis plan, multiplicity handling, detailed censoring rules, and handling of missing outcome information. The record defines the primary population as participants who received study medication, but does not provide further detail about how incomplete follow-up or missing assessments were handled.
The safety entries are descriptive and do not include a control group. The registry record does not report deaths for the listed safety group, and does not provide event timing, duration, or attribution detail in the registry record. The serious-event percentages should not be interpreted as causal or comparative estimates. These limitations restrict what can be concluded from this registry record, without implying that unreported analyses or procedures were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Avastin (Bevacizumab) and Transarterial Chemoembolisation (TACE) Treatment in Patients With Liver Cancer — NCT00576199.
- Registry record last updated 2014-08-29; status last verified 2014-08.
- Results first posted 2014-08-29.
- 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.
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18. Record Summary
The registry record describes NCT00576199, a completed Phase II, multicentre, open-label, single-arm study sponsored by Hoffmann-La Roche. It enrolled 30 participants with localized unresectable hepatocellular carcinoma and assessed bevacizumab administered around TACE. The primary outcome was median progression-free survival, defined from the first study-drug administration to documented progression or death, whichever occurred first.
The record specifies a 95% confidence interval for the primary outcome but does not report its numerical estimate or interval. It lists 6 outcome measures and 0 analysis entries. Safety entries report 17 participants affected by serious adverse events and list six serious-event terms, each at 6.7%. With no comparator group and no reported efficacy estimates, the record supports description of the study design and reported safety observations, but not a treatment comparison.