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 Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Previously Hormone Responsive Metastatic Breast Ca. (NCT00240071), a na phase 2 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00240071 |
| Phase | Phase 2 |
| Condition | Metastatic Breast 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 | University of Alabama at Birmingham |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with metastatic breast cancer who had previously responded to hormonal therapy. Its title and summary frame the clinical question around acquired resistance to hormone treatment. The registry record states that all participants entered onto the study, described as the intention-to-treat population, were analyzed for the primary outcome. Enrollment was 30.
Intervention
Participants continued the same hormonal therapy they had used before study enrollment and combined it with Avastin (bevacizumab). The study sought to assess whether adding bevacizumab could reverse acquired hormone-therapy resistance, using progression-free survival as the primary outcome, and to evaluate toxicity of the combination.
Comparator
The registry describes a single-group study, with no allocation to a separate comparator group. It does not describe a concurrent control arm or a randomized comparison. Consequently, the study record does not establish a like-for-like comparison of combination treatment against hormonal therapy alone.
Primary question
The primary outcome was progression-free survival, measured from registration until documented disease progression or death from any cause, whichever occurred first. The intended question was whether the observed time to progression or death was consistent with the aim of reversing acquired hormone-therapy resistance. The registry record does not report the median progression-free survival or its confidence interval, so the primary result cannot be quantified from the record.
3. Trial Design
This was a Phase II, single-group study sponsored by the University of Alabama at Birmingham. The registry lists enrollment of 30 and a completed status. The recorded start was 2005-10, and primary completion was 2009-03. The condition listed was metastatic breast cancer.
The study combined Avastin (bevacizumab) with hormonal therapy. The arm description says participants continued the same hormonal therapy used before enrollment and added Avastin. The registry identifies no allocation to different groups and no masking. It therefore describes neither a randomized treatment comparison nor a blinded comparison. The intervention was assessed in one group, rather than against a concurrent control group described in the record.
The primary outcome was progression-free survival, defined as the time from registration until the first documented disease progression or death from any cause, whichever came first. The listed timeframe uses the same starting point and event definition. The stated analysis population was all participants entered onto the study, identified as intention to treat.
Objective response rate, defined in the registry as the rate of complete and partial responses, was listed as a secondary outcome. The record indicates two outcome measures but does not provide a numerical response result in the information available for this analysis. It also does not report the detailed eligibility criteria, the particular hormonal regimens used by participants, or the duration of follow-up. Those details are not reported in the registry record.
The single-group design is important when interpreting the study question. A result within this group can describe outcomes among participants receiving the combination, but without a concurrent control group it cannot by itself isolate the effect of bevacizumab from the effect of continued hormonal therapy, the underlying course of disease, or other influences. The registry record does not report a protocol-level sample-size justification or a detailed statistical analysis plan.
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 purpose of this study is to determine if acquired hormone therapy resistance can be reversed by Avastin (Bevacizumab), as measured by time to disease progression and evaluate toxicity of the combination of hormone treatment plus Avastin.
Overall Study
| Stage | Avastin(Bevacizumab) Plus Hormonal Therapy |
|---|---|
| STARTED | 30 |
| COMPLETED | 27 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Avastin(Bevacizumab) Plus Hormonal Therapy |
|---|---|
| Withdrawal by Subject | 3 |
Analysis population for the primary outcome, as defined in the registry: All participants entered onto study (intention to treat) (ITT) were analyzed.
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 | Avastin(Bevacizumab) Plus Hormonal Therapy |
|---|---|---|
| Participants analysed | 30 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 19 |
| Age, Categorical: >=65 years | Participants | 11 |
| Age, Continuous | years | 59.7 (SD 16) |
| Sex: Female, Male: Female | Participants | 30 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over From date of registration until disease progression or death, whichever occurs first.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) is the primary endpoint. In this study it was defined as the time from registration until the first documented disease progression or death from any cause, whichever occurred first. The registry lists the unit as days and specifies the median and a 95% confidence interval as the summary measures. It states that all participants entered onto the study, described as the intention-to-treat population, were analyzed.
In general, a time-to-event endpoint uses both the timing of an event and whether an event has occurred during follow-up. It can therefore convey information about how long participants remain free of the defined event, rather than only counting how many experience it. Combining progression and death into one endpoint also means that either event qualifies; the registry's definition does not treat them as separate primary outcomes.
In general, the median time-to-event value marks the point at which the estimated event-free proportion reaches one half. A confidence interval expresses uncertainty around the estimated quantity. Its width is relevant to precision: a wider interval indicates more uncertainty than a narrower one. These are general interpretations of the statistical measures, not claims about the trial's unreported estimate.
The registry record does not report a numerical median PFS or its 95% confidence interval. It also does not report the number of progression events, the number of deaths contributing to PFS, or the follow-up distribution. As a result, the endpoint definition is clear, but its estimated value and precision cannot be assessed from the registry information recorded.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes an investigation of bevacizumab added to continued hormonal therapy in metastatic breast cancer after prior response to hormonal therapy. Its stated aim was to assess whether acquired hormone-therapy resistance could be reversed, with progression-free survival as the primary endpoint and toxicity of the combination also under evaluation. This describes the research question, not a demonstrated treatment effect.
The primary endpoint has a clear event definition: time from registration to documented progression or death, whichever occurred first. The record also states that the median and a 95% confidence interval were the intended summary. However, neither the numerical median nor its confidence interval appears in the recorded results available for this analysis. There is therefore no reported PFS estimate to interpret, and the precision of that estimate cannot be described.
The record identifies a secondary outcome of objective response rate, defined as complete and partial responses. It does not report a numerical result for that outcome in the available information. No response estimate or precision statement can therefore be discussed. The registry indicates two outcome measures overall, but the information does not provide results for both.
The study included one group and does not describe a concurrent comparator. Outcomes among participants receiving the combination would be descriptive of that group. Without a control group, the design cannot distinguish the contribution of bevacizumab from continued hormonal therapy or other influences on progression and death. There is no basis in the record for a like-for-like treatment comparison.
Safety reporting lists 7 serious adverse events among 30 at risk and 24 other adverse events among 30 at risk for the Avastin plus hormonal therapy group. The record lists 0 deaths in that group. It also gives percentages for selected serious adverse-event terms, including Grade III hypertension at 13.3%. These are safety observations in the treated group; they do not establish how event frequency compares with another treatment. The record does not provide the adverse-event observation period or further detail sufficient to interpret the listed terms as comparative risks.
Overall, the registry record establishes the design, population framing, endpoint definition, and some safety counts. It does not supply a numerical primary-outcome estimate, a control-group result, or detailed analysis results. The posted information consequently supports a description of what the study set out to assess and what safety counts it recorded, but not a quantified conclusion about the primary outcome or a causal comparison.
9. Statistical Methods Explained
The registry identifies progression-free survival as the primary endpoint and gives its definition and intended summaries. It does not report enough numerical outcome information to reconstruct or evaluate the sponsor's primary analysis. The following concepts explain how the stated measures are generally interpreted; they do not describe unreported methods as if they had been used.
What a time-to-event endpoint represents
In general, time-to-event analysis considers the duration until a defined event occurs. Here, the event is the first documented disease progression or death from any cause, and the time origin is registration. A participant who experiences either event contributes an event time under that definition. In many studies, some participants have not had the event by their last known follow-up; their observation is then incomplete for the event time. Methods can account for such incomplete follow-up, but the registry record does not report how follow-up or censoring was handled in this study.
The endpoint combines progression and death. It does not, by itself, distinguish how many participants had progression from how many died before documented progression. The registry supplies no such event breakdown for PFS. The safety record lists deaths separately, but those are not a substitute for the primary endpoint event count or its analysis.
How to read a median and confidence interval
The registry specifies a median PFS with a 95% confidence interval. In general, the median is a central time-to-event summary: it is the point at which the estimated probability of remaining free of the event reaches one half. It is not the average time for every participant, and it does not describe each individual's course.
In general, a 95% confidence interval communicates uncertainty in an estimate under the assumptions of the statistical procedure. It gives a range of values compatible with the observed data and method at the stated confidence level. A more precise estimate tends to have a narrower interval; a less precise estimate tends to have a wider interval. The actual median and interval are not reported in the registry record, so neither their location nor their width can be evaluated.
What a single-group design can establish
In general, a single-group trial can describe outcomes observed among participants receiving a specified intervention. A comparison of those outcomes with an external expectation may be informative in some settings, but it is not equivalent to a concurrent randomized comparison. Differences in participant characteristics, follow-up, care, or outcome ascertainment can make external comparisons difficult to interpret.
This study's record identifies one group receiving Avastin with hormonal therapy and no allocation to a separate control group. The arm description says that participants continued the hormonal therapy used before enrollment. The study can therefore be described as assessing outcomes during the combination regimen. The registry information does not allow a treatment contrast that isolates the addition of Avastin.
What the record says about analysis
The primary-outcome population is stated as all participants entered onto the study, described as intention to treat. In general, an intention-to-treat population aims to retain participants in the group to which they were assigned or entered, according to the trial's analysis rules. Because this is a single-group study, the registry's wording identifies the population but does not provide detail about exclusions, missing outcome information, or specific analysis procedures.
The registry record does not report a numerical PFS result, a hazard ratio, or a detailed statistical model for the primary endpoint. It also does not describe interim analyses, a sample-size justification, or adjustments for multiple outcomes. No such methods should be inferred from the endpoint label alone.
Planning illustrations are not trial results
In general, sample-size planning asks how many participants or events may be needed to detect a specified effect under stated assumptions. The planning assumptions recorded for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; time-to-event illustrations use a total event count. They are planning assumptions, not a description of this trial's single-group design, and the record explicitly characterizes the illustrations as based on the observed effect rather than the trial's own design.
Such planning quantities are not observed power and do not replace the trial's actual estimates or uncertainty intervals. The record does not give the numerical values of the planning illustrations in the information available for this analysis. Nor does it report the observed effect needed to interpret them. No sample-size result or effect estimate can therefore be stated.
In general, a confidence interval and a significance test answer related but different questions. A test evaluates compatibility with a specified null hypothesis under a statistical model, whereas an interval displays a range of plausible parameter values under the method. Neither measure alone resolves limitations of a single-group design. Here, the absence of the primary estimate and interval, along with the absence of a comparator, limits both precision assessment and causal interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists progression-free survival as the primary outcome and objective response rate as a secondary outcome. It defines the secondary outcome as the rate of complete and partial responses. It does not report a multiplicity strategy, such as how interpretation would account for examining more than one outcome. That approach is not reported in the registry record.
In general, multiplicity arises when several outcomes or statistical tests are considered. Repeated testing can increase the chance of at least one apparently notable result even if no corresponding effect exists. Prespecified priorities and adjustment methods can help clarify how multiple findings should be interpreted. The registry identifies a primary and secondary outcome, but it does not provide a complete testing hierarchy or adjustment procedure.
The primary analysis population is stated as all participants entered onto the study, described as intention to treat. The record does not report how missing PFS observations, incomplete follow-up, withdrawals, or missing response assessments were handled. It also does not report the amount or pattern of missing outcome data. These details are not reported in the registry record.
In general, missing-data methods matter because participants with unavailable outcomes may differ from those with observed outcomes. The direction and extent of any resulting bias depend on why information is missing and how the analysis handles it. Without information about missingness and analysis rules, the effect of incomplete data cannot be assessed for this study.
The registry indicates two outcome measures and no analyses recorded in the available information. It does not provide a detailed statistical analysis plan, interim-analysis information, or an account of outcome-specific populations. These omissions limit assessment of how analysis decisions were prespecified and how all measured outcomes were handled.
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 |
|---|---|---|---|
| Avastin(Bevacizumab) Plus Hormonal Therapy | 7 | 30 | 23.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Avastin(Bevacizumab) Plus Hormonal Therapy | 0 of 30 |
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 |
|---|---|
| Avastin(Bevacizumab) Plus Hormonal Therapy | 24 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Avastin(Bevacizumab) Plus Hormonal Therapy |
|---|---|---|
| Grade III hypertension | Vascular disorders | 4 of 30 |
| Grade III fatigue | General disorders | 2 of 30 |
| Grade III syncope | General disorders | 2 of 30 |
| Grade III dyspnea on exertion | Respiratory, thoracic and mediastinal disorders | 2 of 30 |
| Grade III diarrhea | Gastrointestinal disorders | 1 of 30 |
| Grade III leg ulcer | Skin and subcutaneous tissue disorders | 1 of 30 |
| Grade III neuropathy | Nervous system disorders | 1 of 30 |
| Knee and foot pain | Musculoskeletal and connective tissue disorders | 1 of 30 |
| Hyperkalemia | Metabolism and nutrition disorders | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Avastin(Bevacizumab) Plus Hormonal Therapy |
|---|---|---|
| Proteinuria | Renal and urinary disorders | 10 of 30 |
| Nausea and vomiting | Gastrointestinal disorders | 8 of 30 |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 7 of 30 |
| Fatigue | General disorders | 6 of 30 |
| Transaminitits | Gastrointestinal disorders | 4 of 30 |
| Hypertension | Vascular disorders | 4 of 30 |
| Epistaxis | Ear and labyrinth disorders | 4 of 30 |
| Weight loss | General disorders | 4 of 30 |
| Mucositis | Gastrointestinal disorders | 4 of 30 |
| Diarrhea | Gastrointestinal disorders | 3 of 30 |
Serious events with the highest arm-level rate: grade iii hypertension (13.3%), grade iii fatigue (6.7%), grade iii syncope (6.7%), grade iii dyspnea on exertion (6.7%), grade iii diarrhea (3.3%).
The registry lists one group, Avastin (bevacizumab) plus hormonal therapy, with 30 participants at risk for serious adverse events and 7 affected. For other adverse events, it lists 30 at risk and 24 affected. It records 0 deaths in the group. These are the posted counts and should be read as safety observations for this group, not as comparisons with another treatment.
The record also lists selected serious adverse-event terms with percentages: Grade III hypertension, 13.3%; Grade III fatigue, 6.7%; Grade III syncope, 6.7%; Grade III dyspnea on exertion, 6.7%; Grade III diarrhea, 3.3%; and Grade III leg ulcer, 3.3%. These percentages are reported as listed, not recalculated. The registry does not describe the event-observation period in the information.
In general, a count of participants affected and a count of events are not always interchangeable; a participant may have more than one event. The record does not clarify whether the listed terms overlap within participants or how repeated events were counted. It also does not provide a control-group safety profile. Accordingly, these figures describe the recorded safety experience in the treated group, but do not establish comparative risk or explain whether a particular event was attributed to one component of the combination.
12. What the Result Does, and Does Not, Mean
The study's stated purpose was to assess whether acquired hormone-therapy resistance could be reversed by adding Avastin (bevacizumab) to hormonal therapy, while measuring progression-free survival and evaluating toxicity. The record describes the intervention and defines the primary endpoint. It does not report the numerical primary-outcome result, so the magnitude and precision of PFS cannot be stated.
The registry also identifies objective response rate as a secondary outcome, defined as complete and partial responses. A numerical response result is not reported in the available record. Thus the posted information does not permit a quantitative account of response or a comparison between response and progression-free survival.
Because the study is single group, it does not provide a concurrent control outcome. Even if a numerical outcome estimate were available, an outcome observed during the combination regimen would not by itself show what would have happened to comparable participants receiving hormonal therapy without bevacizumab. The registry record does not support a causal estimate of the added effect of bevacizumab.
The safety counts and listed serious-event terms describe recorded events in the combination group. They do not establish whether the combination has more or fewer events than an alternative regimen, and the record does not provide the comparison needed to answer that question. The recorded 0 deaths is a safety entry for the group; it is not a substitute for the PFS result, whose event definition includes either progression or death.
In general, a trial result should be interpreted in light of the estimate, its precision, the design, and the analysis population. Here, the registry provides the design and outcome definitions but not the numerical primary result or detailed outcome analysis. The study's stated aim should therefore be distinguished from evidence that the aim was achieved. The available information describes what was investigated and some safety reporting; it does not establish that resistance was reversed or that the treatment did or did not produce a particular clinical effect.
13. Why This Trial Matters Statistically
This study raises a statistical question that is important whenever a treatment is added to an existing therapy: how much of the observed outcome can be attributed to the addition? The registry describes continued hormonal therapy plus bevacizumab in a single group. Without a concurrent comparator, the outcome can describe the group but cannot isolate the contribution of bevacizumab from the ongoing hormonal therapy or other influences.
The primary endpoint is time to progression or death, rather than a simple count at one assessment point. In general, time-to-event methods can use information about when events occur and account for incomplete follow-up under specified assumptions. That makes the endpoint potentially informative about timing, but also makes details of event ascertainment and follow-up important. The registry defines the event and time origin, while the handling of incomplete follow-up is not reported.
Precision is another central issue. The registry specifies a median and a 95% confidence interval, which would allow readers to consider both the estimated PFS and its uncertainty. Neither numerical value is reported in the available record. Without them, statistical precision cannot be evaluated, regardless of the study's stated objective.
The study also illustrates the distinction between planned analyses and evidence. Planning assumptions can support design decisions, but they do not substitute for observed outcome estimates. The registry's planning-illustration assumptions do not amount to the trial's own design justification, which is not reported. Nor can an illustration be treated as observed power or as proof of a result.
Finally, safety counts require context. The record gives event counts and percentages for selected serious terms, but no concurrent safety comparison or observation period. Statistical interpretation depends not only on the count but on how events were defined, collected, and followed. These design and reporting features determine what conclusions the record can support.
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 principal limitation for interpreting the primary outcome is that the registry record does not report a numerical median progression-free survival or its 95% confidence interval. The definition and intended summary are present, but the estimate and its precision cannot be evaluated. The record also does not give the number of PFS events or separate progression from death within the primary endpoint.
The design is single group, with no allocation to a separate comparator arm. The registry therefore does not provide a concurrent comparison against hormonal therapy alone or another regimen. This limits causal interpretation of outcomes observed with the combination. The record does not describe a randomized comparison.
Although objective response rate is listed as a secondary outcome, a numerical result is not reported in the available information. The registry does not report the outcome results in enough detail to evaluate the secondary measure alongside PFS. It also does not provide information about the duration or completeness of follow-up, missing outcome data, or the handling of incomplete observations.
Safety interpretation is limited by the absence of a comparator and by missing context about the event-observation period. The record lists counts and percentages, but does not clarify whether serious-event terms could overlap in individual participants or how repeated events were treated. Attribution to bevacizumab, hormonal therapy, or their combination is not described in the information available.
Detailed eligibility criteria, the specific hormonal therapies used, the statistical analysis plan, multiplicity handling, interim analyses, and the trial's sample-size justification are not reported in the registry record. These limitations concern interpretation of this trial specifically; they should not be filled in by assumptions about common Phase II practice.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Avastin (Bevacizumab) to Reverse Acquired Estrogen Independence in Previously Hormone Responsive Metastatic Breast Ca. — NCT00240071.
- Registry record last updated 2019-10-30; status last verified 2019-10.
- Results first posted 2011-09-27.
- 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
NCT00240071 is a completed Phase II, single-group study sponsored by the University of Alabama at Birmingham. It enrolled 30 participants with metastatic breast cancer, as listed in the registry. The recorded start was 2005-10, and primary completion was 2009-03.
Participants continued the hormonal therapy used before enrollment and added Avastin (bevacizumab). The primary outcome was progression-free survival, defined from registration to documented progression or death from any cause, whichever occurred first. The stated analysis population was all participants entered onto the study, described as intention to treat. Objective response rate was listed as a secondary outcome.
The registry record does not report a numerical primary-outcome estimate or confidence interval in the information available for this analysis. It lists 7 serious adverse events and 24 other adverse events among 30 at risk, with 0 deaths recorded in the treatment group. The single-group design provides no concurrent comparator for estimating a treatment contrast.