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 Bavituximab and Sorafenib In Patients With Advanced Liver Cancer (NCT01264705), a non-randomized phase 1, phase 2 study. The primary outcome is Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01264705 |
| Phase | Phase 1, Phase 2 |
| Condition | Hepatocellular Carcinoma, Liver Cancer |
| Allocation | Non-Randomized |
| Design model | Sequential |
| Masking | None (open label) |
| Enrollment | 47 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Texas Southwestern Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with advanced hepatocellular carcinoma (HCC). The registry record defines advanced disease as disease not amenable to surgical resection or orthotopic liver transplantation, or disease that is metastatic. Enrollment was 47. The record describes a single-institution trial at the University of Texas Southwestern Medical Center.
Intervention
Participants received bavituximab with sorafenib in one of three bavituximab dose cohorts. The listed weekly bavituximab doses were 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg; sorafenib was listed as 400mg PO twice daily in each cohort.
Comparator
The study was non-randomized and had no masking. The record does not describe a concurrent control group receiving a different treatment or no treatment. Differences among the dose cohorts therefore do not constitute a randomized, like-for-like treatment comparison.
Primary question
The stated primary endpoint was median radiographic time to progression (TTP), measured from treatment initiation to the first evidence of disease progression or last follow-up. The endpoint was intended to describe the time until progression in the analyzed population. The registry record does not report a median TTP or its confidence interval, so it does not give a numerical answer to that endpoint question.
3. Trial Design
This was a phase I/II, non-randomized, open-label therapeutic trial of bavituximab plus sorafenib in advanced HCC. The registry lists a sequential model and no masking. Enrollment was 47, and the study status is completed. The record identifies the University of Texas Southwestern Medical Center as the sponsor and describes a single-institution study.
Three dose cohorts are described. Cohort 1 received bavituximab 0.3 mg/kg weekly with sorafenib 400mg PO twice daily; Cohort 2 received bavituximab 1.0 mg/kg weekly with the same listed sorafenib schedule; Cohort 3 received bavituximab 3.0 mg/kg weekly with the same listed sorafenib schedule. These cohort descriptions identify dose levels, not randomized treatment assignments.
The primary endpoint was median radiographic TTP, with the stated measurement period beginning at treatment initiation and ending at first evidence of progression or last follow-up. The record says that Cohorts 1 and 2 were part of phase I and that this outcome was not collected in phase I. It also says that the three participants who received the 3.0 mg/kg dose were part of phase I and were not part of phase II, and consequently their data were not analyzed for this endpoint. The registry does not report the analyzed phase II endpoint results.
The listed study dates are 2011-01 for start and 2018-04 for primary completion. The record does not report the rationale for the cohort sequence, dose-selection criteria, or a sample-size justification. Details of allocation within cohorts beyond the non-randomized sequential design are 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 | Bavituximab:0.3 mg/kg Weekly Sorafenib: 400mg PO Twice Daily | Bavituximab: 1.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily | Bavituximab: 3.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily |
|---|---|---|---|
| STARTED | 3 | 3 | 41 |
| COMPLETED | 3 | 3 | 41 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Cohort 1 and 2 were part of phase 1 study and at the phase 1 study this outcome was not collected. The 3 participants who received dose Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily were part of phase 1 and hence they were not part of phase 2 . Hence their data were not analyzed here.
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 | Bavituximab:0.3 mg/kg Weekly Sorafenib: 400mg PO Twice Daily | Bavituximab: 1.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily | Bavituximab: 3.0 mg/kg Weekly Sorafenib: 400mg PO Twice Daily | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 41 | 47 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 33 | 37 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 8 | 10 |
| Sex: Female, Male: Female | Participants | 1 | 1 | 7 | 9 |
| Sex: Female, Male: Male | Participants | 2 | 2 | 34 | 38 |
| Race/Ethnicity, Customized: Black | Participants | 1 | 0 | 16 | 17 |
| Race/Ethnicity, Customized: White | Participants | 1 | 0 | 13 | 14 |
| Race/Ethnicity, Customized: Hispanic | Participants | 1 | 2 | 10 | 13 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 1 | 2 | 3 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up., measured over Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was median radiographic time to progression (TTP). It measures the time from treatment initiation to the first evidence of disease progression, with last follow-up used as the endpoint for participants without a recorded progression by their last observation. The registry describes the endpoint as assessed with the Kaplan-Meier method and gives an average timeframe of 24 months.
In general, a time-to-event endpoint can retain information from participants who have not yet had the event when observation ends: their time is censored at their last follow-up rather than treated as if progression had occurred. The median is the point in the estimated event-time distribution by which half of the population is estimated to have experienced the event. It is a summary of the distribution, not a description of every participant's course.
TTP is used to characterize how long progression takes within a defined study population. It is distinct from overall survival, which the registry lists as a secondary outcome, and from disease-specific survival, also listed as secondary. The endpoint description says its 95% confidence intervals were calculated using Greenwood's formula. However, the registry record does not report the median TTP, a confidence interval, the number of progression events, or the number censored. The endpoint therefore cannot be quantitatively interpreted from the registry record alone.
The population note also limits the endpoint's scope: phase I participants in Cohorts 1 and 2 did not have this outcome collected, and the three phase I participants in Cohort 3 were excluded from the phase II endpoint analysis. No other endpoint analysis population details are reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record names a primary endpoint and describes its method, but does not report a median TTP or its 95% confidence interval. There is therefore no posted numerical estimate from which to describe the observed time to progression, its precision, or its variation across participants. The record also lists zero analyses. No hazard ratio or other sponsor-reported comparative estimate is included.
In general, a median time-to-event estimate is more informative when read alongside its confidence interval and the follow-up and event information supporting it. A confidence interval expresses statistical uncertainty in an estimate under the analysis assumptions; it is not a range containing a fixed proportion of individual participants' event times. Because neither endpoint estimate nor interval is reported, the extent of uncertainty around TTP cannot be assessed from this record.
The design further constrains interpretation. This was a non-randomized, open-label, sequential study with dose cohorts, rather than a randomized comparison against a control. Cohort differences could reflect factors other than dose, and the record does not describe an analysis that adjusts for such differences. The cohorts should not be read as a like-for-like treatment comparison. There is also no basis in the posted endpoint information for attributing a change in progression timing to either study drug.
The endpoint population was not all enrolled participants: the record says the phase I outcome was not collected for Cohorts 1 and 2, and that three Cohort 3 participants from phase I were not included in the phase II endpoint analysis. The number of participants contributing to the primary endpoint estimate is not reported in the registry record. This prevents a reader from relating any hypothetical estimate to an explicit analysis denominator.
Safety information is listed separately by cohort. The record reports zero participants with a treatment-related serious adverse event in each cohort, and reports other adverse events for Cohort 3. These counts do not fill the gap in the primary endpoint results and should not be interpreted as a comparison of safety between doses. In general, event counts depend on the groups assessed, definitions, observation period, and completeness of reporting. Some of those details are not reported in the registry record.
Consequently, the posted information supports a description of study design, endpoint definition, and selected adverse-event counts, but not a numerical conclusion about TTP or comparative treatment effects. The absence of a registry result is not evidence that progression did or did not occur at a particular rate or time.
9. Statistical Methods Explained
The registry describes a time-to-event endpoint analyzed with the Kaplan-Meier method. In general, this method estimates the probability of remaining free of the event over time while accounting for participants whose event status is not observed through the end of their follow-up. Such participants are censored at their last known observation. Censoring is not itself an event; it indicates that the event time is not known beyond that point.
What does the median represent?
For a time-to-event distribution, the median is the time at which the estimated event-free probability reaches the midpoint of the distribution. It summarizes the estimated timing of events in the analyzed population. It is not the arithmetic average of individual event times, and it does not imply that every participant has an event at or near the median. The registry's primary endpoint is median radiographic TTP, measured from treatment initiation to first evidence of progression or last follow-up.
The record states that the endpoint used the Kaplan-Meier method but does not report the estimated median. It also does not provide the number of progression events, the number censored, or the endpoint analysis population size. These omissions prevent a reader from checking how much information underlies the estimate or from describing its empirical follow-up pattern.
How should the confidence interval be read?
The record specifies 95% confidence intervals for TTP and says they were calculated using Greenwood's formula. In general, a confidence interval conveys uncertainty about an estimated quantity under the statistical model and procedure used. A narrower interval indicates greater precision than a wider interval, while an interval's location indicates the range of values compatible with the data under that procedure. It is not a prediction interval for an individual participant.
Greenwood's formula is a general method for estimating uncertainty in Kaplan-Meier survival probabilities. The registry identifies it as the basis for the confidence intervals, but it does not provide those intervals or explain any additional interval construction choices. As a result, the precision of the TTP estimate cannot be assessed from the registry record.
Why does the analysis population matter?
Time-to-event estimates depend on which participants are included and how their observation times are defined. The registry notes that Cohorts 1 and 2 were part of phase I, when this outcome was not collected. It also notes that three participants who received bavituximab 3.0 mg/kg weekly with sorafenib were part of phase I and were not part of phase II, so their data were not analyzed for this endpoint. The record does not specify the full endpoint analysis denominator or provide further inclusion and exclusion rules.
In general, results for a subset of a trial population describe that subset, not automatically every enrolled participant. A clear analysis population is important because exclusions or unavailable outcome measurements can affect both the relevance and interpretation of the estimate. The registry does not provide enough information to assess the effect of these endpoint-specific exclusions.
What does the design allow?
The trial is described as non-randomized, open-label, and sequential, with three bavituximab dose cohorts and a shared listed sorafenib schedule. In general, random assignment helps make groups comparable with respect to measured and unmeasured characteristics. Without randomization, differences between cohorts may be associated with participant characteristics, timing, or other factors as well as dose. An open-label design also means masking was absent, though the record does not describe whether or how that could have influenced outcome assessment.
The registry does not report an inferential comparison of dose cohorts, a model for adjusted comparisons, or a hazard ratio. It reports zero analyses. No comparative estimate should be inferred from the cohort descriptions alone. The record also does not report details of interim analyses, prespecified statistical testing procedures, or a sample-size justification; those design features should not be guessed.
In general, time-to-event methods rely on the timing and censoring information being recorded and on assumptions about censoring. If censoring is related to the unobserved event risk in ways the analysis does not account for, the estimate may be difficult to interpret. The registry record does not report diagnostics or sensitivity analyses addressing this issue. The method named for the endpoint is therefore identifiable, but the analysis details and numerical result needed for an independent statistical appraisal are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary endpoint, median radiographic TTP, and several secondary outcomes, including safety, overall survival, and disease-specific survival. Multiple outcomes can create multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase if testing is not accounted for. In general, investigators may address multiplicity through a prespecified hierarchy, adjusted significance thresholds, or an explicitly exploratory interpretation. The registry record does not report a multiplicity strategy or a statistical testing plan.
The record lists zero analyses. It does not report p-values, hazard ratios, confidence intervals for secondary outcomes, or numerical results for the primary endpoint. Thus, there are no posted hypothesis-test results to interpret, and no multiplicity adjustment can be assessed. The registry also does not report whether any interim analyses were planned or conducted.
Missing outcome information is particularly relevant to the primary endpoint. The record says TTP was not collected for phase I participants in Cohorts 1 and 2, and that three phase I participants in Cohort 3 were not included in the phase II endpoint analysis. It does not report the full analysis population, reasons for any other unavailable endpoint observations, or a missing-data strategy. In general, censored follow-up in a time-to-event analysis differs from an unrecorded outcome: censoring uses the known time through last follow-up, while missingness may mean that the necessary information is unavailable. The registry does not provide enough detail to characterize any such missingness.
The number of enrolled participants is 47, but the number contributing to the primary endpoint analysis is not reported in the registry record. The registry also does not describe an intention-to-treat population or another named analysis population. These gaps limit assessment of how enrollment, endpoint collection, and analysis populations relate to one another.
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 |
|---|---|---|---|
| Cohort 1 | 0 | 3 | 0.0% |
| Cohort 2 | 0 | 3 | 0.0% |
| Cohort 3 | 0 | 41 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 | 0 of 3 |
| Cohort 2 | 0 of 3 |
| Cohort 3 | 38 of 41 |
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 |
|---|---|
| Cohort 1 | 0 of 3 |
| Cohort 2 | 0 of 3 |
| Cohort 3 | 12 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 12 of 41 |
| fatigue | General disorders | 0 of 3 | 0 of 3 | 10 of 41 |
| anorexia | Metabolism and nutrition disorders | 0 of 3 | 0 of 3 | 9 of 41 |
| abdominal cramping | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 7 of 41 |
| hypertension | Cardiac disorders | 0 of 3 | 0 of 3 | 5 of 41 |
| vomiting | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 4 of 41 |
| Hand /foot syndrome | Skin and subcutaneous tissue disorders | 0 of 3 | 0 of 3 | 4 of 41 |
| nausea | General disorders | 0 of 3 | 0 of 3 | 3 of 41 |
| Gerd | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 2 of 41 |
| stomstitis | Immune system disorders | 0 of 3 | 0 of 3 | 2 of 41 |
The safety listing gives counts by cohort. Cohort 1 had 3 participants at risk for the serious-event measure and 0 with a treatment-related serious adverse event; Cohort 2 had 3 at risk and 0 with such an event. Cohort 3 had 41 at risk and 0 with a treatment-related serious adverse event. For other adverse events, the record lists 3 at risk and 0 affected in each of Cohorts 1 and 2, and 41 at risk with 12 affected in Cohort 3. The record lists 0 deaths in Cohorts 1 and 2 and 38 in Cohort 3.
These are descriptive counts, not a randomized safety comparison. The cohort sizes differ, and the study was non-randomized. The record does not describe the observation period or provide details about event definitions, collection procedures, or severity for the other adverse events. No top serious adverse-event terms are listed. A count of zero treatment-related serious events in a cohort means none were recorded in that category for the listed group; it does not establish that a treatment has no risk or that the cohorts are comparable.
The listed deaths in Cohort 3 are a separate field from treatment-related serious adverse events. The registry record does not state that those deaths were caused by treatment. The counts should be read as posted group-level observations, not as evidence of causality.
12. What the Result Does, and Does Not, Mean
The record establishes that a non-randomized phase I/II study evaluated bavituximab at three weekly dose levels with sorafenib in advanced HCC. It also identifies median radiographic TTP as the primary endpoint and states that Kaplan-Meier methods were used, with Greenwood's formula for 95% confidence intervals. These details explain what the investigators intended to measure and the broad method named for the endpoint.
What the record does not establish is a numerical TTP result. It reports neither the median nor its confidence interval, and it lists zero analyses. No estimate of progression timing, uncertainty, or dose-cohort difference can therefore be described from the posted results. This absence should not be interpreted as a favorable or unfavorable endpoint outcome.
The study design also does not support a causal comparison of the three dose cohorts. Participants were not randomized, the study was open-label, and the registry describes a sequential model. In general, observed differences between non-randomized cohorts can reflect characteristics other than the intervention level. The record does not report an adjusted comparative analysis that would address such differences.
The endpoint population was limited by collection and phase information: phase I participants in Cohorts 1 and 2 did not have this outcome collected, and the three phase I participants in Cohort 3 were not included in the phase II analysis. The full analyzed denominator is not reported in the registry record. These details matter when considering how closely the endpoint results, if available, would represent the enrolled population.
The safety listing supplies counts for treatment-related serious adverse events, other adverse events, and deaths by cohort, but does not give enough context to establish causation or compare risks reliably. Overall, the registry record describes the trial structure and selected safety counts, but does not provide the numerical primary endpoint findings needed to judge the observed TTP or its precision. No conclusion about whether a treatment works or does not work follows from these reported details alone.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly named endpoint is not the same as a fully interpretable result. Median radiographic TTP is specified, and the record names Kaplan-Meier estimation and Greenwood's formula for uncertainty. Yet without the median, confidence interval, event information, or full analysis population, the endpoint's magnitude and precision cannot be assessed. Statistical interpretation depends not only on the method label but also on the estimate and the information supporting it.
The record also highlights the distinction between dose cohorts and randomized comparison groups. Three bavituximab dose levels are described alongside the same sorafenib schedule, but allocation was non-randomized and sequential. In general, randomization is important for interpreting group differences because it helps separate treatment assignment from participant characteristics. Dose cohorts in this design should not be treated as equivalent to randomized arms.
Outcome collection can also differ across phases. The registry explicitly says the primary endpoint was not collected for phase I participants in Cohorts 1 and 2 and that three phase I participants in Cohort 3 were not analyzed for the phase II endpoint. Such information makes endpoint-specific analysis populations essential to interpretation. Their size and full selection rules are not reported in the registry record.
Finally, the study's posted safety counts and its absent efficacy estimate answer different questions. Descriptive adverse-event counts do not substitute for a time-to-progression result, and neither establishes a causal treatment effect in a non-randomized study. The record is a useful example of how study design, endpoint availability, and reporting completeness jointly determine what can be inferred statistically.
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 record constrain interpretation. First, the primary endpoint is described but its numerical result is not reported in the registry record. There is no median TTP, confidence interval, event count, or censoring count to evaluate. The registry lists zero analyses, and no hazard ratio or other comparative estimate is posted.
Second, the primary endpoint population differs from the overall enrollment. The record says TTP was not collected in phase I for Cohorts 1 and 2 and that three phase I participants in Cohort 3 were not included in the phase II analysis. The total number analyzed and the other endpoint inclusion rules are not reported. This makes it difficult to assess the scope and completeness of the endpoint data.
Third, the study was non-randomized, open-label, and sequential. As a result, dose cohorts are not like-for-like control groups, and the record does not describe an adjusted analysis to support cohort comparisons. The registry does not report a sample-size justification, statistical testing plan, multiplicity strategy, or interim analysis details.
Finally, the safety counts are not accompanied by detailed event definitions, observation periods, or explanatory context for the deaths listed. No top serious adverse-event terms are listed. The registry does not state that deaths were treatment-related. These limitations mean the counts should remain descriptive and should not be interpreted as comparative or causal evidence.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Bavituximab and Sorafenib In Patients With Advanced Liver Cancer — NCT01264705.
- Registry record last updated 2020-11-12; status last verified 2020-10.
- Results first posted 2020-11-12.
- 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.
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18. Record Summary
The registry record describes a completed, non-randomized, open-label phase I/II study of bavituximab with sorafenib in advanced HCC. Enrollment was 47. Three cohorts received weekly bavituximab at 0.3 mg/kg, 1.0 mg/kg, or 3.0 mg/kg, with sorafenib 400mg PO twice daily listed for each.
The primary endpoint was median radiographic TTP from treatment initiation to first evidence of progression or last follow-up. The record identifies Kaplan-Meier estimation and Greenwood's formula for 95% confidence intervals, but does not report the median or interval. It states that phase I participants in Cohorts 1 and 2 did not have this endpoint collected and that three phase I participants in Cohort 3 were not included in the phase II endpoint analysis.
Safety counts are listed by cohort, while the registry lists zero analyses. The non-randomized design and missing endpoint results prevent a quantitative interpretation of TTP or a causal comparison between dose cohorts.