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 High-dose Bevacizumab in Advanced Renal Carcinoma Patients (NCT00455975), a non-randomized phase 2 study. The primary outcome is Progression-free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00455975 |
| Phase | Phase 2 |
| Condition | Renal Cancer, Kidney Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 119 |
| Arms in the primary outcome | n/a |
| Lead sponsor | SCRI Development Innovations, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced clear cell renal carcinoma. The registry record lists renal cancer and kidney cancer as conditions and records enrollment of 119 participants.
Intervention
Bevacizumab 15mg/kg intravenously every week, continued until progressive disease or toxicity.
Comparator
A separate, nonrandomized arm received bevacizumab 15mg/kg intravenously every 2 weeks, also until progressive disease or toxicity. This is not a like-for-like control comparison.
Primary question
What is the median progression-free survival under the study regimen, measured from the first day of study drug administration to progression or death on study?
The trial was designed to examine the effectiveness and side effects of two higher dosing schedules of bevacizumab. Its primary endpoint was progression-free survival, with a stated expected timeframe of 18 months. The registry record defines progression using RECIST v1.1 criteria. It also lists overall survival, objective response rate, and overall tolerability and toxicity as secondary outcomes.
The registry record does not report the median progression-free survival, its confidence interval, or the results for the secondary outcomes. It therefore does not supply the estimates needed to answer how long participants remained progression-free or to compare outcomes across the two schedules. Because allocation was nonrandomized, any observed differences between arms would not, by themselves, establish that dosing schedule caused those differences. The record explicitly cautions that the arms are not a like-for-like control comparison.
3. Trial Design
This was a phase II, parallel, nonrandomized trial with no masking. The registry record describes one drug, bevacizumab, administered in two schedules. The weekly arm used bevacizumab 15mg/kg intravenously every week; the bi-weekly arm used 15mg/kg intravenously every 2 weeks. In both arms, treatment was to continue until progressive disease or toxicity.
The registry record lists enrollment of 119 participants and marks the study as completed. The recorded start was 2007-02 and the primary completion was 2013-07. Those dates describe the registry timeline; they do not establish the duration of follow-up for an individual participant. The primary endpoint has an expected timeframe of 18 months, but the actual follow-up and the number of participants assessed at each time are not reported in the registry record.
Nonrandomized allocation means the record does not describe participants being assigned to the two schedules by chance. Differences between groups could therefore reflect differences in who entered each arm, as well as any schedule-related effect. The registry record gives no adjustment method or other information that would resolve such differences. It specifically notes that the arms are not a like-for-like control comparison.
The sponsor is SCRI Development Innovations, LLC. The listed intervention is bevacizumab. Overall survival, objective response rate, and overall tolerability and toxicity are listed as secondary outcomes, alongside the primary progression-free survival endpoint. The record lists four outcome measures and zero analyses. It does not report the sample-size justification, enrollment targets by arm, or an analysis plan. These design details should not be inferred from the completed status or the recorded enrollment.
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 | Weekly Avastin | Bi-weekly Avastin |
|---|---|---|
| STARTED | 58 | 61 |
| COMPLETED | 40 | 40 |
| NOT COMPLETED | 18 | 21 |
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.
| Characteristic | Unit | Weekly Avastin | Bi-weekly Avastin | Total |
|---|---|---|---|---|
| Participants analysed | 58 | 61 | 119 | |
| Age, Continuous | years | 65 (44 to 88) | 60 (40 to 88) | 63 (40 to 88) |
| Sex: Female, Male: Female | Participants | 24 | 17 | 41 |
| Sex: Female, Male: Male | Participants | 34 | 44 | 78 |
| Region of Enrollment: United States | participants | 58 | 61 | 119 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival, measured over 18 months (expected).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival is the time from Day 1 of study drug administration to disease progression as defined by RECIST v1.1, or death on study. The registry definition describes progression as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. The stated unit is months, and the planned summary measure is the median with a 95% confidence interval.
As a general statistical explanation, a time-to-event endpoint uses both the time until an event and information about participants who have not yet had the event by the time their follow-up ends. The median is the time by which half of the relevant population has experienced the event, according to the survival estimate. It can summarize the timing of progression or death without assuming that all participants have the same follow-up.
Progression-free survival is used in clinical trials to capture disease progression and death in a single time-to-event outcome. The registry record does not report the median, confidence interval, number of events, or the analysis population for this endpoint. The stated 18 months is an expected timeframe, not a reported endpoint result or a description of each participant’s follow-up.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the trial question and endpoint but does not report a primary endpoint estimate. In particular, it gives no median progression-free survival and no 95% confidence interval. It therefore does not show the observed duration of progression-free survival or the precision of an estimate. The expected timeframe of 18 months is a planning description, not an outcome value.
The record also does not give hazard ratios, p-values, or other analysis results. No statistical conclusion about differences in progression-free survival between schedules can be drawn from the information in the record. The secondary outcomes—overall survival, objective response rate, and overall tolerability and toxicity—are named, but their results are not reported in the registry record.
The design matters for interpretation. Allocation was nonrandomized, and the registry record warns that the two arms are not a like-for-like control comparison. As a general statistical point, random allocation can help balance both measured and unmeasured participant characteristics between study arms. Without it, arm differences may arise from baseline differences or other factors, and an unadjusted comparison cannot isolate a causal effect of schedule. The registry record does not report participant characteristics or an adjustment strategy that would clarify the extent of this concern.
Safety reporting includes serious adverse event counts for each arm and a set of listed serious event terms with percentages. These are descriptive registry entries; they do not establish that a schedule caused an event or permit a complete comparison of safety. The record does not report deaths in the adverse-event grouping. It also does not provide detail about the timing, duration, or clinical course of the listed events.
The record lists four outcome measures and zero analyses. That distinction is important: naming an endpoint is not the same as reporting its result. Without estimates and their uncertainty, readers cannot assess the magnitude or precision of outcomes from this registry entry. The appropriate interpretation is therefore limited to the recorded design, outcome definitions, and adverse-event counts, with efficacy results not reported in the registry record.
9. Statistical Methods Explained
Progression-free survival is a time-to-event outcome. In general, time-to-event analyses account for the fact that participants may have different amounts of observation and that some may leave observation without a recorded event. The registry record specifies the event definition and a median with a 95% confidence interval as the planned summary. It does not report the method used to estimate that median, how censoring was handled, or the resulting estimate.
What does a median time-to-event estimate describe?
As a general statistical explanation, the median time-to-event estimate marks the point at which the estimated event-free proportion reaches one half. It describes a feature of the estimated distribution of event times; it is not the average time for every participant and does not mean that all participants experience an event at that time. In this trial, the event combines RECIST v1.1 progression or death on study. The median progression-free survival is not reported in the registry record, so the value cannot be interpreted from this entry.
How should a confidence interval be read?
As a general explanation, a confidence interval expresses uncertainty around an estimated quantity under the statistical method used. A narrower interval indicates greater precision than a wider interval, while neither the interval nor the estimate alone establishes that an outcome is clinically important. The record names a 95% confidence interval for the median but does not report its limits. No numerical statement about precision is possible without those limits.
What would a hazard ratio add?
As a general statistical explanation, a hazard ratio compares the event rate at a given time between groups, subject to the assumptions of the model used. It is not the same as a ratio of medians or a simple comparison of the proportion experiencing an event. Interpretation would require an estimate, its uncertainty, and context about the analysis. Although the record description indicates that sponsor-reported hazard ratios are the relevant source for time-to-event comparisons, no hazard ratio or related analysis result is reported in the registry record.
Why does nonrandomized allocation matter?
As a general principle, randomized allocation supports comparison by reducing systematic differences between groups at entry. In a nonrandomized study, participants in separate arms can differ in ways that also relate to outcome. Statistical adjustment may address measured characteristics, but cannot automatically remove bias from unmeasured factors. The registry record calls this a nonrandomized comparison and says the arms are not like-for-like controls. It does not report an adjustment model or baseline comparison, so the extent to which any potential differences were addressed is not known.
What do the planning illustrations represent?
The registry record describes sample-size planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For time-to-event illustrations, the stated calculation concerns the total number of events and uses the Schoenfeld method; other illustrations refer to participants per arm. These are planning illustrations, not evidence that the trial was designed using those assumptions, and not observed power. The trial’s own sample-size justification is not reported in the registry record. The actual illustration values and an observed effect are not reported in the registry record.
As a general statistical explanation, a planning calculation describes the sample size or event count associated with specified assumptions. It does not show the probability that a completed trial has found a real effect, and it cannot substitute for the estimate and confidence interval from the analysis. The record does not report an observed primary endpoint effect from which to evaluate the illustrations.
How do event counts differ from time-to-event results?
A simple count records how many participants or events were recorded under a category. A time-to-event analysis additionally uses the timing of events and follow-up. Counts alone do not provide a median time, a hazard ratio, or a description of how the event pattern changed over time. The adverse-event entries in the registry record should therefore be read separately from the unreported progression-free survival analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists progression-free survival as the primary outcome and lists overall survival, objective response rate, and overall tolerability and toxicity as secondary outcomes. It records four outcome measures and zero analyses. No multiplicity procedure is reported in the registry record. It is therefore not possible to determine whether the trial planned to adjust for testing multiple outcomes, how any testing sequence was to work, or how the reported confidence intervals and p-values were intended to be interpreted across outcomes.
As a general statistical explanation, evaluating multiple endpoints can increase the chance of finding an apparently notable result by chance if each is tested without accounting for the set of tests. A prespecified testing strategy can help clarify which conclusions are confirmatory and how uncertainty should be interpreted. The registry record does not describe such a strategy, and it reports no outcome analyses. No claim about statistical significance or multiplicity-adjusted inference can be made from this entry.
Missing-data handling is also not reported in the registry record. For the time-to-event endpoint, the entry does not describe censoring rules, losses to follow-up, or how incomplete observations were treated. It does not state the analysis population for progression-free survival or the secondary outcomes, such as whether analyses included all enrolled participants or another defined group. The listed enrollment and adverse-event denominators do not supply that missing analysis-population information.
As a general point, missingness and analysis-population definitions can affect both the amount of information available and the interpretation of estimates. Without the relevant rules and results, readers cannot assess whether missing observations may have influenced an outcome estimate. The registry record does not report enough information to evaluate these issues.
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 |
|---|---|---|---|
| Weekly Avastin | 33 | 58 | 56.9% |
| Bi-weekly Avastin | 35 | 61 | 57.4% |
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 |
|---|---|
| Weekly Avastin | 58 of 58 |
| Bi-weekly Avastin | 61 of 61 |
Most frequent serious adverse event terms
| Event term | Organ system | Weekly Avastin | Bi-weekly Avastin |
|---|---|---|---|
| Dehydration | Metabolism and nutrition disorders | 2 of 58 | 2 of 61 |
| General disorders and administration site conditions - Other, disease progression | General disorders | 2 of 58 | 2 of 61 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 2 of 58 | 1 of 61 |
| Thromboembolic event | Vascular disorders | 2 of 58 | 1 of 61 |
| Urinary Tract Infection | Infections and infestations | 0 of 58 | 3 of 61 |
| Nausea | Gastrointestinal disorders | 1 of 58 | 1 of 61 |
| Confusion | Psychiatric disorders | 1 of 58 | 1 of 61 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 58 | 1 of 61 |
| Fracture | Injury, poisoning and procedural complications | 1 of 58 | 1 of 61 |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | 2 of 58 | 0 of 61 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Weekly Avastin | Bi-weekly Avastin |
|---|---|---|---|
| FATIGUE | General disorders | 37 of 58 | 50 of 61 |
| PROTEINURIA | Renal and urinary disorders | 34 of 58 | 39 of 61 |
| NAUSEA | Gastrointestinal disorders | 21 of 58 | 22 of 61 |
| Anorexia | Metabolism and nutrition disorders | 14 of 58 | 24 of 61 |
| HEADACHE | Nervous system disorders | 18 of 58 | 17 of 61 |
| DYSPNEA | Respiratory, thoracic and mediastinal disorders | 16 of 58 | 17 of 61 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 12 of 58 | 19 of 61 |
| HYPERTENSION | Vascular disorders | 30 of 58 | 0 of 61 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 9 of 58 | 21 of 61 |
| Constipation | Gastrointestinal disorders | 10 of 58 | 16 of 61 |
Serious events with the highest arm-level rate: urinary tract infection (4.9%), dehydration (3.4%), general disorders and administration site conditions - other, disease progression (3.4%), pain in extremity (3.4%), thromboembolic event (3.4%).
The registry record lists serious adverse events by arm. In the weekly arm, 58 participants were at risk and 33 were recorded as affected. In the bi-weekly arm, 61 were at risk and 35 were recorded as affected. These are the registry’s counts; they are not a comparison adjusted for differences between the nonrandomized arms.
The record lists urinary tract infection at 4.9%. It lists dehydration, disease progression under general disorders and administration site conditions, pain in extremity, thromboembolic event, and generalized muscle weakness at 3.4% each. These percentages are presented as serious event terms. The registry entry does not describe the event-level denominator, timing, duration, or whether a participant could contribute more than one event term. They should not be interpreted as a complete account of all safety outcomes.
The separate “other” adverse-event grouping records 58 affected among 58 at risk in the weekly arm and 61 affected among 61 at risk in the bi-weekly arm. The record does not give further detail in this entry to clarify the breadth of that grouping. It reports no death counts for the adverse-event groups. These registry figures are descriptive and do not establish that bevacizumab or either schedule caused an event.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II study examined two bevacizumab schedules in advanced clear cell renal carcinoma. It specifies the schedule in each arm, the progression-free survival definition, and selected safety counts. It also records that the study is completed and that enrollment was 119.
It does not report the result needed to quantify the primary endpoint: the median progression-free survival and its 95% confidence interval are absent. It likewise does not report analyses for the listed secondary outcomes. Consequently, the record cannot establish the observed outcome under either schedule, the degree of uncertainty around an estimate, or whether outcomes differed between arms.
The trial’s nonrandomized allocation limits what an arm comparison could mean even if estimates were available. As a general statistical principle, an observed difference between nonrandomized groups can reflect participant differences or other influences, not only the treatment schedule. The registry record itself warns that the arms are not like-for-like controls. No adjusted estimates or details of a strategy to address confounding are reported.
These limitations do not make the record uninformative. It documents the study question, treatment schedules, endpoint definition, and certain safety counts, and it identifies outcomes for which results would be relevant. But the entry is not a report of efficacy estimates or a causal comparison. It does not show that one schedule is better, equivalent, or worse than the other, and it does not support a treatment recommendation. Such conclusions would require reported outcome analyses and an appropriate understanding of the study design and its limitations.
13. Why This Trial Matters Statistically
This trial illustrates a distinction central to clinical biostatistics: a registered outcome definition is not an outcome result. The record carefully identifies progression-free survival as the primary endpoint, defines progression using RECIST v1.1, names the time origin, and specifies a median and 95% confidence interval. Yet it does not report the median or interval. Without those estimates, readers can understand what was intended to be measured but cannot quantify the observed result or its precision.
The design also highlights how allocation affects interpretation. The two arms differ in dosing interval, but allocation was nonrandomized, and the registry record cautions against treating them as like-for-like controls. As a general principle, a statistical comparison is not automatically causal simply because results are reported by arm. The design and any adjustment strategy influence what an estimated difference can support.
The record’s safety entries offer another useful distinction: adverse-event counts and percentages are descriptive, while a comparative safety conclusion requires more information about denominators, event definitions, overlap, follow-up, and group comparability. The record does not resolve all of these details. Nor does it report the analyses for the listed efficacy and safety outcomes.
Finally, planning calculations should not be confused with results. The record describes sample-size illustrations based on an observed effect and specified assumptions, but those illustrations are not observed power and are not evidence that the trial met a planned target. The trial’s own design justification is not reported in the registry record. Together, these points show why interpretation depends not only on the endpoint name or enrollment, but on the estimates, uncertainty, analysis methods, and design context actually reported.
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 direct limitation of the registry entry is the absence of primary endpoint results. Although the primary endpoint and its intended summary are defined, the median progression-free survival and 95% confidence interval are not reported in the registry record. No hazard ratios, p-values, or other efficacy estimates are available in this entry. The named secondary outcomes also have no results.
Nonrandomized allocation is a trial-specific concern because the two schedules are not a like-for-like control comparison. The record does not report baseline characteristics, an adjustment method, or analyses that might help readers assess differences between arms. Any comparison of their outcomes would need to account for this design limitation; the registry entry does not provide the information needed to do so.
The record does not describe the analysis population, endpoint-specific participant numbers, follow-up distribution, censoring rules, or handling of missing data. It also does not report the trial’s sample-size justification, multiplicity approach, or statistical analysis plan. The expected endpoint timeframe does not indicate the actual follow-up achieved.
Safety information is limited to the recorded serious adverse-event counts and selected event terms with percentages. The entry does not provide further detail about timing, recurrence, severity grading, event overlap, or the denominator used for the listed percentages. Death counts are recorded as unavailable for these adverse-event groupings. These limits constrain interpretation of the safety entries and prevent a complete assessment of comparative safety from this record alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: High-dose Bevacizumab in Advanced Renal Carcinoma Patients — NCT00455975.
- Registry record last updated 2014-12-22; status last verified 2014-12.
- Results first posted 2014-12-22.
- 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
This completed phase II study enrolled 119 participants with advanced clear cell renal carcinoma and examined bevacizumab administered weekly or every 2 weeks. Allocation was nonrandomized, masking was absent, and the registry record cautions that the arms are not like-for-like controls. Both schedules used bevacizumab 15mg/kg intravenously until progressive disease or toxicity.
The primary outcome was median progression-free survival, defined from the first day of study drug to RECIST v1.1 progression or death on study, with a 95% confidence interval and an expected timeframe of 18 months. Overall survival, objective response rate, and overall tolerability and toxicity were listed as secondary outcomes. The primary estimate, secondary outcome results, and analyses are not reported in the registry record.
The record includes serious adverse-event counts and selected serious event terms, but does not report enough detail to support a causal or complete comparison of safety. The trial’s own sample-size justification, missing-data approach, analysis populations, and multiplicity plan are also not reported in the registry record.