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 Phase II Study of Doxorubicin and Avastin® in Sarcoma. (NCT00755261), a na phase 2 study. The primary outcome is RECIST.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00755261 |
| Phase | Phase 2 |
| Condition | Sarcoma, Soft Tissue Sarcoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced soft-tissue sarcomas were the intended population. The registry record reports that 4 subjects enrolled before the study was terminated because of low accrual. It does not report participant characteristics or the eligibility criteria needed to describe who could enter the study in detail.
Intervention
The single study group received Avastin and doxorubicin. The regimen description specifies Avastin 15 mg/kg by IV infusion plus doxorubicin 60 mg/M2 by IV 6-hour infusion on Day 1 of each 21-day treatment cycle. Dose changes could be made in response to toxicities or patient tolerance.
Comparator
There was no separate comparator group in this single-group study. Although the study rationale asked whether adding Avastin to a doxorubicin regimen might improve outcomes, the design does not provide a concurrent group receiving doxorubicin alone or another control regimen. A comparative treatment effect therefore cannot be estimated from this study design.
Primary question
The stated question concerned whether adding Avastin to doxorubicin could improve overall survival and slow disease progression, while also evaluating the safety of the combination. The primary outcome is labeled RECIST, with a timeframe of 6 month PFS. No outcome value, estimate, uncertainty interval, or analysis is reported in the registry record, so the study does not answer the efficacy question in the posted results.
3. Trial Design
This was a Phase II, single-group study of Avastin and doxorubicin for patients with advanced soft-tissue sarcomas. The registry lists allocation as NA, masking as NONE, and the model as SINGLE GROUP. These design details mean the record does not describe random assignment, blinding, or a concurrent control group. The stated regimen combined Avastin 15 mg/kg IV infusion with doxorubicin 60 mg/M2 by IV 6-hour infusion on Day 1 of each 21-day treatment cycle. Dose reductions or modifications were to be applied as indicated by toxicities or patient tolerance.
The study began in 2008-09, and the recorded primary completion date is 2010-09. Its status is TERMINATED. The primary outcome description says the study was terminated because of low accrual; the population text records 4 subjects enrolled/2 years. The registry does not explain recruitment procedures, the planned enrollment target, or why accrual was low. A sample-size justification is not reported in the registry record.
The design could describe outcomes and safety experiences among the participants treated, but a single-group design cannot isolate the effect of adding Avastin from the effect of doxorubicin, the course of the disease, or other influences. With enrollment limited to the reported 4 subjects and no outcome analysis listed, the registry record does not support a comparative conclusion. The statistical plan, including any planned estimand, analysis population, or methods for accounting for follow-up, is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Avastin and Doxorubicin |
|---|---|
| STARTED | 6 |
| COMPLETED | 4 |
| NOT COMPLETED | 2 |
Analysis population for the primary outcome, as defined in the registry: study was terminated because of low accrual (4 subjects enrolled/2 years)
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 and Doxorubicin |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 58 (45 to 65) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 4 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as RECIST, measured over 6 month PFS.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is labeled RECIST, and its timeframe is listed as 6 month PFS. The record gives no unit, parameter, dispersion measure, or numerical outcome result. It also does not describe the assessment schedule, the criteria used to define progression, or how missing assessments would be handled. Thus, the registry label identifies the intended outcome area but does not provide an analyzable estimate of progression-free survival at the stated timeframe.
In general, progression-free survival is used to describe how long participants remain alive without recorded disease progression, under definitions set by a study protocol. It can be useful in a clinical trial because it focuses on disease progression as well as survival, and it may summarize the course of illness over follow-up. Interpretation depends on the event definition, timing and frequency of assessments, censoring rules, and analysis method. Those details are not reported in the registry record.
RECIST appears as the outcome title, but the record does not report a response count, a proportion, a time-to-event estimate, or any other result under that title. The primary outcome description instead explains why the study ended. That administrative explanation is not an endpoint result. Without posted outcome data, readers cannot assess the observed 6 month PFS, its precision, or whether the intended outcome was evaluated for the enrolled participants.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical fact is that the registry record lists 4 enrolled subjects and reports that the study was terminated because of low accrual. It lists one outcome measure and no analyses. The primary outcome is labeled RECIST, with a timeframe of 6 month PFS, but there is no posted endpoint value, estimate, confidence interval, or test result. Consequently, no estimate of the combination's effect on progression-free survival can be interpreted from this record.
The study was single-group, with no randomized or concurrent comparator. Even if an outcome estimate for the treated group were available, it would describe that group's observed experience rather than establish what would have happened under a different regimen. A treatment contrast requires a suitable comparison. Differences from historical expectations would not substitute for a concurrent comparison unless the protocol and analysis justified that approach; such a plan is not reported in the registry record.
Precision is also a central concern. In general, an estimate based on few observations can be highly uncertain, and the uncertainty interval is important for judging the range of values compatible with the data. The registry record does not post an estimate or interval, so precision cannot be assessed. It is not appropriate to infer an effect from the study's Phase II designation, its intended question, or its completion status.
The record's safety information reports 4 participants at risk for serious adverse events and 2 with serious adverse events in the Avastin and Doxorubicin group. It separately reports 4 at risk for other adverse events and 1 affected. The listed serious terms are febrile neutropenia and acute renal failure, each with a reported frequency of 25.0%. These counts describe the small group recorded; they do not establish comparative safety, and the record does not provide event-level timing, exposure duration, attribution, or a comparison group.
The sample-size assumptions describe planning illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not make the study randomized or turn an unreported outcome into an observed effect. The record provides no outcome estimate on which to base an interpretation, and the planning illustrations are not the trial's own design justification. Overall, the posted information is insufficient to estimate efficacy or compare safety between treatments.
9. Statistical Methods Explained
The registry record identifies a single-group Phase II study, with allocation listed as NA and masking listed as NONE. These are design descriptions, not statistical evidence of benefit or harm. Because no concurrent comparison group is listed, the data cannot directly estimate a contrast between the combination and another treatment. The outcome record also lists no analyses. The statistical plan, analysis populations, and approach to follow-up are not reported in the registry record.
What does a single-group design estimate?
In general, a single-group study can describe measurements observed among people who received the study regimen. A treatment effect, however, is a contrast between outcomes under different treatment conditions. The participants' observed outcomes under one regimen do not reveal their unobserved outcomes under an alternative regimen. A control group, randomization, or a carefully justified external comparison may address some of this problem, but the registry record does not describe any such comparison. The listed design therefore does not support a causal estimate of the effect of adding Avastin.
What is needed to interpret a time-to-event outcome?
In general, a time-to-event analysis uses information about when an event occurs and about participants who have not had the event by the end of observation or who leave observation earlier. The analysis depends on the event definition, follow-up, censoring rules, and statistical method. The primary outcome timeframe is listed as 6 month PFS, but the record does not report individual event times, an estimate, or the rules used to determine progression and censoring. It is therefore not possible to reconstruct or evaluate a time-to-event analysis from the posted record.
A confidence interval, in general, communicates statistical uncertainty around an estimate under the assumptions of the analysis. Its width reflects precision: a wider interval is less precise than a narrower one. No confidence interval or other uncertainty measure for the primary outcome is reported in the registry record. No p-value or test result is reported either. The absence of those statistics means that neither the magnitude nor the precision of a primary outcome estimate can be assessed.
Why do planning assumptions not replace trial results?
The registry includes sample-size assumptions for planning illustrations: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the stated output is the total number of events; other illustrations give participants per arm. These are assumptions for planning illustrations, not evidence that the trial enrolled two arms, followed the assumed allocation, or observed the effect used in the illustrations. The record does not report a trial-specific sample-size justification.
In general, a sample-size calculation asks how much information a planned study would need under specified assumptions. It does not show that a study had a particular probability of finding a result after it has been conducted. That distinction matters particularly when an outcome estimate is not reported. The sample-size assumptions cannot be treated as observed power, nor can a planning illustration establish the outcome of this study.
Why does over-dispersion matter in general?
In general, over-dispersion means that observed variation is greater than a model expects. When a model assumes less variation than the data contain, uncertainty can be understated and statistical tests can be misleading. The appropriate approach depends on the outcome and model. The registry record does not report a statistical model or a dispersion assessment, so it is not possible to say whether over-dispersion was relevant to the planned analysis or how it was handled.
What can the adverse-event counts support?
Counts and percentages can describe recorded events in the group, but interpretation depends on how events were defined, collected, and attributed, as well as the amount of time participants were observed and treated. The registry record reports the number at risk and the number affected for serious and other adverse events. It does not report a comparative safety analysis, exposure-adjusted rates, event timing, or participant-level records. These descriptive counts should not be read as a treatment comparison or as a complete characterization of risk.
In general, a statistical analysis plan would clarify the primary estimand, outcome definition, analysis population, handling of missing observations, censoring, and multiplicity. These choices affect what an estimate means and how uncertainty is quantified. Such a plan is not reported in the registry record. Given the absence of endpoint results and analysis details, readers cannot verify whether an analysis was conducted as planned or evaluate its assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one outcome measure and no analyses. It does not report a statistical analysis plan or identify a family of confirmatory hypotheses. Multiplicity refers, in general, to the increased chance of at least one false-positive finding when multiple outcomes, comparisons, or repeated tests are considered. Whether an adjustment was needed, or how it would have been performed, is not reported in the registry record. The existence of one listed outcome measure alone does not establish that only one analysis was planned or conducted.
Missing-data methods are not described. The record does not report how many participants had an evaluable primary outcome, whether any outcome assessments were missing, how withdrawals or incomplete follow-up were handled, or whether sensitivity analyses were planned. These details are important for interpreting a time-to-event outcome, because incomplete follow-up and censoring assumptions can affect the estimate.
The analysis population is also not reported in the registry record. It is not stated whether the primary analysis was intended to include everyone enrolled, only participants who began treatment, or another defined group. The registry records 4 enrolled subjects, but that count alone does not establish how many were included in an endpoint analysis. No primary endpoint analysis is listed, so there is no reported analysis population to evaluate.
In general, clear reporting of multiplicity, missing-data handling, and analysis populations helps readers understand what question an estimate answers and how robust it may be. Those details are unavailable in the registry record, as is the primary endpoint result itself.
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 and Doxorubicin | 2 | 4 | 50.0% |
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 and Doxorubicin | 1 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Avastin and Doxorubicin |
|---|---|---|
| febrile neutropenia | Blood and lymphatic system disorders | 1 of 4 |
| acute renal failure | Renal and urinary disorders | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Avastin and Doxorubicin |
|---|---|---|
| thrush | Infections and infestations | 1 of 4 |
| dehydration | Metabolism and nutrition disorders | 1 of 4 |
| dysphagia -unable to swallow medications | Gastrointestinal disorders | 1 of 4 |
Serious events with the highest arm-level rate: febrile neutropenia (25.0%), acute renal failure (25.0%).
The registry lists 4 participants at risk for serious adverse events in the Avastin and Doxorubicin group, with 2 participants affected. It lists 4 at risk for other adverse events, with 1 affected. The top serious adverse-event terms are febrile neutropenia and acute renal failure, each reported as 25.0%. These figures describe events recorded for the study group; they do not provide a comparison against another regimen.
The record does not clarify whether the serious-event terms refer to distinct participants, whether a participant could contribute more than one event, or how the terms relate to the count of participants with any serious event. It also does not report event onset, duration, severity beyond the serious classification, treatment attribution, exposure time, or the method used to collect events. The reported percentage for each term should be read as listed, not as a comparative risk estimate.
In general, safety findings depend on the observation period and how events are solicited and coded. A small group can only provide limited descriptive information, and the absence of a listed event is not proof that an event cannot occur. The registry record does not report deaths for this group. These safety data cannot establish whether the combination is more or less hazardous than a comparator.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase II, single-group study of Avastin with doxorubicin enrolled 4 subjects and was terminated because of low accrual. It records a primary outcome labeled RECIST with a timeframe of 6 month PFS, but reports no primary outcome result and no analyses. The study's stated efficacy question therefore remains unanswered by the posted results.
The record also gives limited descriptive safety counts: 2 of 4 participants at risk had serious adverse events, and 1 of 4 at risk had other adverse events. Febrile neutropenia and acute renal failure are each listed among the top serious terms at 25.0%. These observations describe what was recorded in this group; they do not quantify an excess risk relative to another regimen or show that every event was caused by the study drugs.
The study does not establish whether adding Avastin changes overall survival, progression-free survival, tumor response, or safety relative to doxorubicin alone. There is no separate comparator group, no posted endpoint estimate, and no uncertainty interval. The enrollment and termination information also do not show whether the regimen had a particular effect. Low accrual explains the recorded reason for termination, not the clinical outcome.
In general, a trial result must be interpreted in light of its design, measured outcomes, analysis methods, and uncertainty. Here, the record supports a description of the study design, enrollment, termination reason, and recorded adverse-event counts. It does not support a conclusion about comparative efficacy or comparative safety. Any sample-size planning illustration is prospective in purpose and cannot substitute for an observed endpoint analysis.
13. Why This Trial Matters Statistically
This study illustrates the difference between a research question and an answer supported by trial data. Its stated question was whether adding Avastin to doxorubicin could improve overall survival and slow progression, while assessing safety. But the registry lists a single-group design, enrollment of 4 subjects, early termination for low accrual, and no outcome analyses. The intended question is therefore not resolved by the record.
That distinction is important in biostatistics because a treatment effect is comparative. Without a control group, an observed outcome under the combination cannot by itself show what would have happened under another regimen. Even a numerical outcome estimate would require careful interpretation of selection, follow-up, and other sources of bias. In this record, the primary outcome estimate itself is not reported.
The record also shows why statistical precision and transparent reporting matter. An endpoint label and timeframe do not reveal the observed outcome, and event counts do not show how uncertain a treatment comparison would be. No confidence interval, test result, or primary analysis is listed. The absence of these results makes it impossible to judge the size or precision of any efficacy effect.
Finally, the planning assumptions should be distinguished from the study's actual design and findings. They describe sample-size illustrations under stated statistical assumptions; they are not a record of a completed comparative analysis. The case underscores that design, accrual, outcome reporting, and analysis all determine what conclusions can be drawn, and that an unreported result should not be replaced by inference.
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.
Several limitations specific to this study restrict interpretation. The registry records a single-group design and no comparator, so the effect of adding Avastin cannot be separated from the course of disease or other factors. Enrollment was 4 subjects, and the study was terminated because of low accrual. The record does not state the planned enrollment target, a recruitment feasibility assessment, or whether the termination decision was made under a prespecified rule.
The primary outcome is labeled RECIST with a timeframe of 6 month PFS, but no outcome value or analysis is reported. The registry record does not describe the progression criteria, assessment timing, censoring rules, or analysis population. A confidence interval, p-value, and treatment-effect estimate are also not reported in the registry record. This prevents evaluation of both the direction and precision of any efficacy finding.
The safety information is limited to participant counts and listed serious adverse-event terms. The registry record does not give exposure duration, event timing, attribution, event-level detail, or comparative rates. The entries do not permit a clear assessment of whether the listed terms occurred in separate participants or how they relate to the overall serious-event count.
The statistical analysis plan, sample-size justification, missing-data methods, and multiplicity approach are not reported in the registry record. The sample-size assumptions are described as planning illustrations based on an observed effect, not as the study's own design. These gaps, along with the absence of endpoint analyses and low accrual, mean the posted information is descriptive rather than a basis for estimating comparative treatment effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase II Study of Doxorubicin and Avastin® in Sarcoma. — NCT00755261.
- Registry record last updated 2015-05-08; status last verified 2015-05.
- Results first posted 2015-05-08.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a Phase II, single-group study of Avastin and doxorubicin for advanced soft-tissue sarcomas. It lists allocation as NA and masking as NONE. The regimen was Avastin 15 mg/kg IV infusion plus doxorubicin 60 mg/M2 by IV 6-hour infusion on Day 1 of each 21-day treatment cycle, with dose modifications as indicated by toxicity or tolerance.
The study started in 2008-09 and has a primary completion date of 2010-09. Its status is TERMINATED. The record states that termination was due to low accrual and reports 4 subjects enrolled/2 years. The primary outcome is labeled RECIST, with a timeframe of 6 month PFS; no outcome result or analysis is listed.
For the Avastin and Doxorubicin group, 2 of 4 participants at risk had serious adverse events, and 1 of 4 had other adverse events. The top serious terms are febrile neutropenia and acute renal failure, each at 25.0%. The record does not provide a concurrent comparator or comparative treatment-effect estimate.