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 Bevacizumab With or Without Fosbretabulin Tromethamine in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer (NCT01305213), a randomized phase 2 study. The primary outcome is Progression-free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01305213 |
| Phase | Phase 2 |
| Condition | Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 107 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. The primary endpoint population is described as all intent-to-treat patients. The registry record reports enrollment of 107.
Intervention
Bevacizumab with fosbretabulin tromethamine. Both drugs were administered intravenously on day 1, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity.
Comparator
Bevacizumab alone, administered intravenously on day 1, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity.
Primary question
What progression-free survival was observed in each randomized arm? The registry record gives a median and 95% confidence interval for each arm, but does not report a sponsor analysis directly comparing the arms for this endpoint.
The clinical question concerns whether adding fosbretabulin tromethamine is associated with a different progression-free survival pattern than bevacizumab alone in this patient group. The trial was randomized and phase II, with a parallel-arm design and no masking reported in the registry record.
Progression-free survival is the primary endpoint. Secondary outcomes listed in the registry record include adverse events, measurable disease and progression-free survival, tumor response, overall survival, and response by CA-125. These outcomes address different aspects of disease course and safety; they are not interchangeable measures of the same effect.
The posted primary results describe each arm separately. Without a reported primary between-arm analysis, the arm-specific medians should not be treated as a formal estimate of the treatment contrast. The posted results can describe the observed outcomes and their precision, but do not by themselves establish whether the arms differ.
3. Trial Design
This is a randomized phase II trial with a parallel design. The registry record lists enrollment of 107 and describes two treatment arms: bevacizumab alone and bevacizumab combined with fosbretabulin tromethamine. The allocation is recorded as randomized. Masking is recorded as none, so the registry record does not describe a blinded comparison.
In Arm I, participants received bevacizumab intravenously over 30–90 minutes on day 1. In Arm II, participants received bevacizumab over 30–90 minutes and fosbretabulin tromethamine over 10–20 minutes on day 1. In both arms, courses repeated every 21 days in the absence of disease progression or unacceptable toxicity.
The trial record lists the conditions as recurrent fallopian tube carcinoma, recurrent ovarian carcinoma, and recurrent primary peritoneal carcinoma. Its broader description includes recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. The sponsor is the National Cancer Institute. The recorded start date is 2011-03-21, the primary completion date is 2016-08-20, and the study status is completed.
The primary endpoint population is identified as all intent-to-treat patients. The arm-level primary results list 53 participants for bevacizumab and 54 for the combination. The registry record does not give a detailed account of the randomization procedure, concealment of allocation, eligibility criteria, or sample-size justification. Those design details are not reported in the registry record.
Because there was no masking, participants and study personnel were not described as blinded to assigned treatment. This is relevant context when considering outcomes that may involve assessment, such as disease response, although the registry record does not specify how assessment bias was addressed. The posted primary results remain descriptive by arm rather than a reported sponsor test of the randomized contrast.
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 | Arm I Bevacizumab | Arm II Bevacizumab + Fosbretabulin |
|---|---|---|
| STARTED | 53 | 54 |
| COMPLETED | 53 | 54 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All intent to treat patients
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 | Arm I Bevacizumab | Arm II Bevacizumab + Fosbretabulin | Total |
|---|---|---|---|---|
| Participants analysed | 53 | 54 | 107 | |
| Age, Continuous | years | 64.3 (SD 12) | 64.9 (SD 10.3) | 64.6 (SD 11.15) |
| Age, Customized: 30 - 39 years | Participants | 2 | 0 | 2 |
| Age, Customized: 40 - 49 years | Participants | 3 | 5 | 8 |
| Age, Customized: 50 - 59 years | Participants | 12 | 12 | 24 |
| Age, Customized: 60 - 69 years | Participants | 19 | 15 | 34 |
| Age, Customized: 70 - 79 years | Participants | 13 | 19 | 32 |
| Age, Customized: > = 80 years | Participants | 4 | 3 | 7 |
| Sex: Female, Male: Female | Participants | 53 | 54 | 107 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS), measured over For those patients whose disease can be evaluated by physical examination, progression was assessed prior to each 21 day cycle. CT scan or MRI if used to follow lesion for measurable disease every other cycle, up to 5 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) is the primary endpoint. It measures the time from randomization until disease progression or death. The registry description also identifies date of last contact for participants without an observed endpoint; those participants are censored. The endpoint timeframe describes progression assessment before each 21-day cycle for patients whose disease could be evaluated by physical examination, and CT scan or MRI every other cycle when used to follow measurable lesions, up to 5 years.
Time-to-event endpoints such as PFS retain information about when an event occurs, rather than recording only whether it occurred by a single assessment date. In general, this can help describe the course of disease over follow-up. Censoring allows participants without an observed progression or death to contribute information up to their last known contact, but interpretation relies on appropriate handling of those observations. The registry record does not report additional details about the censoring assumptions or procedures.
The posted summary is the median PFS for each arm, with a 95% confidence interval. A median is the time by which the estimated event-time distribution reaches its midpoint; it is not an average duration for every participant. The arm-specific medians describe each group, but a direct randomized comparison generally requires an appropriate between-arm analysis. Such a sponsor-reported comparison is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record reports median PFS of 4.83 months (95% confidence interval 4.14 to 6.24) for bevacizumab alone and 7.23 months (95% confidence interval 4.3 to 10.51) for bevacizumab plus fosbretabulin tromethamine. These are arm-specific summaries. The combination arm has the larger posted median, but the medians alone do not quantify a formal treatment effect or establish a difference between randomized arms.
The confidence intervals describe uncertainty around each arm's median under the analysis used. They are not a confidence interval for the difference between arms. A comparison of two arm-specific intervals is not a substitute for a direct treatment-effect analysis, particularly for time-to-event data. The registry record does not report a sponsor hazard ratio or another primary between-arm estimate, and the listed median-time comparison is marked as not estimable for a two-arm comparison.
The primary endpoint is clinically relevant to the trial's question because it records time until progression or death, with censoring for participants who have no observed endpoint. Its interpretation depends on follow-up and event information, which are not fully detailed in the registry record. The posted values should therefore be read as summaries of the recorded trial results, not as a stand-alone verdict about comparative effectiveness.
The secondary response comparisons point in the same direction at the level of their point estimates: the combination arm has higher posted response percentages for both tumor response and response by CA-125. However, the corresponding unadjusted risk-difference confidence intervals include no difference. The unadjusted p-values are 0.469 for tumor response and 0.392 for response by CA-125. These secondary comparisons are not substitutes for the primary PFS analysis, and the registry record does not list sponsor-reported analyses for them.
For these binary outcomes, the calculated risk differences are 0.075 for tumor response and 0.097 for response by CA-125, with respective confidence intervals of -0.127 to 0.277 and -0.127 to 0.320. These are unadjusted recalculations from the posted group summaries, rather than reported sponsor analyses. Their uncertainty is substantial, and the intervals are compatible with differences in either direction as well as little or no difference. They should not be treated as confirmatory evidence.
Overall, the primary results describe longer median PFS in the combination arm, while the registry record does not provide the direct primary comparison needed to assess the magnitude and precision of the between-arm effect. Secondary response point estimates also favor the combination, but their unadjusted comparisons are uncertain. These observations are descriptive and do not establish that one regimen is superior.
9. Statistical Methods Explained
Statistical interpretation depends on distinguishing summaries within each arm from estimates that directly compare the randomized groups. The registry record gives a median PFS and 95% confidence interval separately for each arm. It does not give a sponsor-reported hazard ratio or other direct estimate for the primary comparison. The two medians cannot be subtracted and presented as a trial-estimated treatment effect; the registry record does not supply such a calculation or analysis.
What does a confidence interval convey?
In general, a confidence interval expresses uncertainty in an estimate under the statistical method used. A narrower interval indicates greater precision than a wider interval, while an interval spanning a broad range indicates less precision. A confidence interval is not a range containing every participant's outcome, and it is not a probability statement that the true value lies within the particular interval after the data have been observed.
The PFS confidence intervals apply to the separate arm medians. They do not directly answer whether the randomized treatments differ. For binary secondary outcomes, the registry record posts 90% or 95% confidence intervals for response percentages, while the unadjusted recalculated risk differences have their own intervals. Those contrast intervals include zero, so the posted summaries do not rule out no difference under those calculations. This is not proof that the treatments are equivalent; equivalence requires a design and analysis explicitly aimed at that question.
Why is a median different from a hazard ratio?
In general, the median summarizes a single point on an event-time distribution. A hazard ratio, when reported and appropriate, compares event rates over follow-up under a specified time-to-event model. These statistics answer related but distinct questions and should not be substituted for one another. The registry record's primary-result entries are medians, and no sponsor-reported hazard ratio is reported in the registry record. The statistical meaning entry indicates that only sponsor-reported hazard ratios are used for time-to-event comparisons; consequently, no recalculated primary treatment contrast is presented.
How should the secondary calculations be read?
The tumor-response and CA-125 comparisons include unadjusted recalculations from posted group summaries. For a binary outcome, a risk difference expresses the contrast between the two response proportions. A value of zero represents no difference on that scale; the confidence interval conveys uncertainty around the estimate. The posted intervals for both outcomes cross zero. The corresponding p-values are unadjusted and do not account for the fact that several outcomes are considered.
These recalculations are not sponsor-reported analyses: the registry record lists no reported analyses for the secondary outcomes. They also do not replace an analysis that might account for the trial's design or other prespecified considerations. The discrepancy flag is false, so there is no indicated disagreement between a recalculation and a sponsor result requiring sponsor precedence. However, the absence of a reported sponsor analysis still limits the conclusions that can be drawn from the calculated comparisons.
What do the planning illustrations mean?
In general, sample-size planning asks how many participants would be needed to detect a specified effect under stated design assumptions. The registry record's planning illustrations are based on the observed effect, not on the trial's own design. They assume a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations consider detecting the full observed effect and stated fractions of that effect, and report participants per arm for 80% or 90% power.
Those figures are planning illustrations, not observed power and not evidence that the trial was designed to detect those effects. Because the effect assumptions are derived from observed results, they should not be treated as independent evidence about the likely effect in a future study. The registry record does not report the trial's original sample-size assumptions or justification.
For general context, over-dispersion means that observed variability is greater than a model's assumed variability. It can make standard errors too small and intervals too narrow if the model does not account for it. The registry record does not report whether over-dispersion was assessed or relevant to any analysis in this trial; it should not be assumed to have occurred.
What does censoring contribute?
For PFS, participants without an observed progression or death are censored at the date of last contact, according to the endpoint description. In general, censoring allows available follow-up to contribute information without treating an unobserved event as if it had occurred. The interpretation of a time-to-event estimate depends on how censoring is handled and on assumptions about its relationship to future outcomes. Further censoring details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record identifies the primary endpoint as PFS and lists five secondary outcomes. It reports no analyses in the analysis count, and the secondary outcome entries list no reported analyses. The record does not describe a prespecified testing hierarchy, adjustment for multiple comparisons, or a plan for controlling the chance of false-positive findings across outcomes. Those details are not reported in the registry record.
Multiplicity matters because assessing several outcomes can increase the chance that at least one result appears noteworthy even when there is no true effect. This is a general statistical concern, not evidence that any particular result in this trial is false. The unadjusted secondary comparisons should therefore be interpreted cautiously and should not be read as if they were isolated confirmatory tests.
The primary endpoint population is described as all intent-to-treat patients. The registry record does not provide further detail about exclusions, analysis-set construction, or departures from assigned treatment. The reported arm denominators differ across some outcome summaries, but the reason for those differences is not reported in the registry record. It would be inappropriate to attribute them to missingness, eligibility, or a particular analysis rule without documentation.
The PFS description states that participants without an observed progression or death are censored, and identifies last contact as a relevant date. Additional information about the amount and pattern of censoring, missing assessments, or sensitivity analyses is not reported in the registry record. The record also does not report how missing binary outcome data were handled. These gaps limit assessment of whether missing observations could affect the results.
The registry record does not report an interim-analysis plan, stopping rules, a detailed statistical analysis plan, or the trial's original sample-size justification. This absence does not establish that such procedures were not used; it means they are not reported in the registry record. Consequently, the posted results can be described, but some aspects of the analysis strategy and its prespecification cannot be evaluated from 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 |
|---|---|---|---|
| Arm I Bevacizumab | 9 | 53 | 17.0% |
| Arm II Bevacizumab + Fosbretabulin | 16 | 54 | 29.6% |
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 |
|---|---|
| Arm I Bevacizumab | 53 of 53 |
| Arm II Bevacizumab + Fosbretabulin | 52 of 54 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm I Bevacizumab | Arm II Bevacizumab + Fosbretabulin |
|---|---|---|---|
| Hypertension | Vascular disorders | 1 of 53 | 3 of 54 |
| Atrial Fibrillation | Cardiac disorders | 0 of 53 | 2 of 54 |
| Dehydration | Metabolism and nutrition disorders | 0 of 53 | 2 of 54 |
| Chest Pain - Cardiac | Cardiac disorders | 1 of 53 | 0 of 54 |
| Constipation | Gastrointestinal disorders | 0 of 53 | 1 of 54 |
| Vomiting | Gastrointestinal disorders | 0 of 53 | 1 of 54 |
| Abdominal Pain | Gastrointestinal disorders | 0 of 53 | 1 of 54 |
| Obstruction Gastric | Gastrointestinal disorders | 0 of 53 | 1 of 54 |
| Gastrointestinal Disorders - Other | Gastrointestinal disorders | 0 of 53 | 1 of 54 |
| Ileus | Gastrointestinal disorders | 1 of 53 | 0 of 54 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm I Bevacizumab | Arm II Bevacizumab + Fosbretabulin |
|---|---|---|---|
| Fatigue | General disorders | 35 of 53 | 42 of 54 |
| Hypertension | Vascular disorders | 28 of 53 | 32 of 54 |
| Peripheral Sensory Neuropathy | Nervous system disorders | 26 of 53 | 24 of 54 |
| Nausea | Gastrointestinal disorders | 22 of 53 | 22 of 54 |
| Anemia | Blood and lymphatic system disorders | 23 of 53 | 19 of 54 |
| Constipation | Gastrointestinal disorders | 16 of 53 | 25 of 54 |
| Abdominal Pain | Gastrointestinal disorders | 19 of 53 | 22 of 54 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 23 of 53 | 17 of 54 |
| Headache | Nervous system disorders | 18 of 53 | 21 of 54 |
| Diarrhea | Gastrointestinal disorders | 16 of 53 | 21 of 54 |
Serious events with the highest arm-level rate: hypertension (5.6%), atrial fibrillation (3.7%), dehydration (3.7%), chest pain - cardiac (1.9%), ileus (1.9%).
The registry record reports serious adverse event counts for each arm. In the bevacizumab arm, 9 of 53 participants at risk were affected; in the combination arm, 16 of 54 participants at risk were affected. It also reports other adverse event counts: 53 of 53 participants at risk in the bevacizumab arm and 52 of 54 in the combination arm. These are participant counts, not a comparison adjusted for follow-up or other factors.
The listed serious adverse event terms include hypertension (5.6%), atrial fibrillation (3.7%), dehydration (3.7%), chest pain - cardiac (1.9%), ileus (1.9%), and gastrointestinal fistula (1.9%). The registry record does not specify the arm attribution for these term percentages in the posted summary, so they should not be assigned to a particular arm. Death counts are not reported in the safety summary.
In general, adverse-event counts describe events observed under the trial's recording and follow-up procedures. They do not alone establish that a treatment caused an event or provide a complete comparison of safety between arms. The registry record identifies adverse events of Grade 3 or higher as a secondary outcome, but the posted group counts above should not be mistaken for a full severity-specific analysis.
12. What the Result Does, and Does Not, Mean
The posted primary results show arm-specific PFS medians of 4.83 months for bevacizumab alone and 7.23 months for bevacizumab plus fosbretabulin tromethamine. The corresponding 95% confidence intervals are 4.14 to 6.24 and 4.3 to 10.51. These summaries describe observed trial outcomes and their precision within each arm.
They do not, by themselves, show the size or precision of a randomized treatment effect. A formal primary comparison is not reported in the registry record, and no sponsor-reported hazard ratio is available in the posted results. The arm-specific intervals cannot be used as if they were an interval for a between-arm difference. The larger median in one arm is therefore not sufficient to conclude that the combination changed PFS relative to bevacizumab alone.
The secondary response summaries have point estimates in the same direction, but the unadjusted comparisons are uncertain and no sponsor-reported analyses are listed for those outcomes. Their results do not resolve the limitations of the primary comparison. The adverse-event counts provide descriptive safety information, but they likewise do not establish a causal difference in risk between assigned treatments.
In general, a randomized trial can support a comparative interpretation when the outcome definition, analysis population, and between-arm analysis are sufficiently reported and appropriate. Here, the registry record leaves important details of the statistical analysis and missing-data handling unreported. That limits how far the posted statistics can be interpreted. The results neither establish that one treatment is superior nor demonstrate that the treatments are equivalent.
This statistical interpretation is not medical advice. It describes what the registry record reports and the limits of those reported results; it does not make a treatment recommendation.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why arm-level summaries and direct treatment comparisons must be distinguished. The primary endpoint is a time-to-event measure, but the registry record reports only a median and confidence interval for each arm. The two summaries describe the groups separately; they do not supply a sponsor-reported estimate of the randomized contrast.
The example also illustrates the importance of reporting uncertainty. The arm-specific PFS intervals are not narrow enough to replace a direct comparison, and the secondary binary comparisons have intervals that include no difference. A point estimate can suggest a direction while still carrying substantial uncertainty. Both aspects should be communicated rather than emphasizing the point estimate alone.
Secondary outcomes can add context, but multiple outcomes require caution. Without a reported multiplicity strategy, unadjusted secondary comparisons have less confirmatory weight. Similarly, planning illustrations based on observed effects should be kept separate from the trial's actual design assumptions and should not be described as observed power.
Finally, the record's reporting gaps matter for interpretation. Details about the primary between-arm analysis, original sample-size justification, multiplicity, missing data, and censoring beyond the endpoint description are not reported in the registry record. Their absence does not show that methods were not used, but it limits independent appraisal of the results. Clear reporting of these elements helps readers distinguish a descriptive signal from a precise and well-supported comparative conclusion.
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 registry record affect interpretation. Most importantly, the primary PFS results are posted as separate arm medians and confidence intervals, while a sponsor-reported comparison is not available. The record does not report a hazard ratio or another direct primary treatment-effect estimate. As a result, comparative precision cannot be assessed from the primary results alone.
The registry record does not describe the trial's original sample-size assumptions or justification. The planning illustrations are based on observed effects and are not a substitute for the original design rationale. The detailed statistical analysis plan, any interim analyses, and multiplicity procedures are not reported in the registry record.
The primary endpoint description gives the event definition and states that participants without an endpoint are censored, but further censoring details are not reported. Information about missing assessments, reasons for differing outcome denominators, and the handling of missing data is also not reported in the registry record. These details would help readers assess the robustness of the posted estimates.
The registry record lists no reported analyses for the secondary outcomes. The unadjusted recalculations for binary responses offer descriptive comparisons, but they are not sponsor analyses and do not address multiplicity. The arm-specific safety counts and listed serious-event terms also lack enough detail in the posted summary to support a complete comparative safety assessment; for example, attribution of the listed term percentages by arm is not specified.
These limitations concern what can be evaluated from the registry record. They do not establish that methods or analyses were absent from the trial; those matters are simply not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bevacizumab With or Without Fosbretabulin Tromethamine in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer — NCT01305213.
- Registry record last updated 2019-07-30; status last verified 2019-07.
- Results first posted 2017-07-12.
- 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
NCT01305213 is a completed randomized phase II parallel trial sponsored by the National Cancer Institute. It enrolled 107 participants with recurrent or persistent ovarian, fallopian tube, or primary peritoneal cancer and compared bevacizumab alone with bevacizumab plus fosbretabulin tromethamine. The registry record lists no masking.
The primary endpoint was PFS among all intent-to-treat patients. The registry record posts median PFS and 95% confidence intervals by arm, but does not report a sponsor analysis directly comparing the randomized groups. Secondary outcomes include adverse events, disease response, overall survival, and response by CA-125. The posted results support descriptive interpretation, while the absence of key comparative-analysis details limits conclusions about differences between the treatments.