Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (NCT02979899), a randomized phase 3 study. The primary outcome is Progression Free Survival of Patients With Unresectable Angiosarcoma.

2. Clinical Question

3. Trial Design

The registry describes a randomized, phase 3, parallel-group study with no masking. It compares TRC105 plus Votrient with Votrient alone in patients with advanced angiosarcoma. The enrollment recorded is 128. The study is marked completed. The registry lists a start date of 2017-02-13 and a primary completion date of 2019-04-11.

The combination arm received weekly intravenous TRC105 alongside standard-dose Votrient by mouth once daily. The comparison arm received standard-dose Votrient by mouth once daily. The study description says participants had not previously received pazopanib or TRC105, and that their disease was not suitable for surgery intended to cure. Examples include metastatic or bulky disease and disease for which resection would pose unacceptable risk.

Random allocation is intended, in general, to make assigned groups comparable on average with respect to both measured and unmeasured characteristics. It does not guarantee identical groups in a particular trial. With no masking, participants and study personnel were not blinded to assignment according to the registry entry. That can matter for outcomes influenced by subjective assessments or decisions, although the primary endpoint also relies on imaging review. The registry says progression was assessed by independent radiology review under RECIST v1.1.

The primary endpoint is progression-free survival, expressed as a mean in months with a 95% confidence interval. Its timeframe runs from randomization to first documented progression or death from any cause, assessed through the interim-analysis cutoff, stated as 25 months. The endpoint population is described as all patients randomized by that cutoff. The record does not report the group-specific endpoint values or analysis results, nor does it describe the rationale for the enrollment target or detailed statistical 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients randomized onto study by cut off date of interim analysis

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.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival of Patients With Unresectable Angiosarcoma, measured over from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut off date of interim analysis (25 months).

Progression-free survival measures the time from randomization until either the first documented disease progression or death from any cause, whichever occurs first. The registry defines progression according to RECIST v1.1: a 20% increase in the sum of the longest diameter of target lesions, measurable growth in a non-target lesion, or appearance of new lesions. Progression assessment is described as based on independent radiology review.

This endpoint is used in general to capture how long participants remain alive without documented progression. It combines progression and death into one time-to-event outcome, so either event ends the measured interval. It does not, by itself, describe symptom burden, quality of life, or overall survival separately. The registry lists patient-reported outcomes and overall survival as secondary outcomes.

The primary endpoint is specified as a mean in months with a 95% confidence interval. A mean summarizes the average observed endpoint value under the analysis used; a confidence interval conveys uncertainty around an estimate under the method's assumptions. The record describes assessment up to the interim-analysis cutoff at 25 months, but it does not report the mean, confidence limits, group-level estimates, or a treatment comparison. It is therefore not possible to quantify the observed progression-free survival or its precision from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized phase 3 study with a parallel design and no masking. The concepts below explain how such design and endpoint choices are generally interpreted; they are not claims about unreported procedures in this trial.

What does random allocation contribute?

In general, random allocation aims to distribute prognostic factors across treatment groups without relying on investigators to choose assignment. This helps reduce systematic differences at baseline and supports comparisons by assigned group. It cannot ensure that groups are identical, especially in a particular study, and it does not remove uncertainty from the estimated treatment contrast. The registry reports randomization but does not state its sequence-generation or allocation-concealment procedures, so those details are not reported in the registry record.

What does an open-label design mean?

Masking was none, so the record describes an unmasked trial. In general, knowledge of assignment can influence care, reporting, or assessment, particularly when outcomes depend on judgment. The primary endpoint uses a defined progression criterion and the record specifies independent radiology review. That feature is relevant to assessment, but the registry does not provide further operational details about review, disagreements, or masking of image reviewers. Such details are not reported in the registry record.

How is progression-free survival interpreted?

Progression-free survival is a time-to-event measure. Each participant's time begins at randomization and ends at the first qualifying event, progression or death, according to the stated definition. In general, time-to-event analyses can also include participants whose event has not been observed by the end of follow-up; their information is handled as censored rather than treated as if the event occurred at the last observation. The record does not state how censoring, loss to follow-up, or incomplete assessments were handled, so no particular approach should be assumed.

The registry specifies the primary summary as a mean in months with a 95% confidence interval. A confidence interval is a range of values compatible with the observed data under a specified statistical procedure and its assumptions. It communicates estimation uncertainty; it is not a guarantee that the true value lies in the interval. The registry record does not report the interval, the estimated means, or the calculation method. Time-to-event outcomes can be summarized in different ways, and the particular estimand and method matter. The record's use of a mean does not disclose whether or how the analysis addressed incomplete follow-up.

Why does the endpoint definition matter?

A prespecified endpoint definition determines what counts as an event and when the measurement starts. Here, the record defines progression through RECIST v1.1 criteria and includes death from any cause as an event. Such a composite endpoint is commonly used in general when both disease progression and death are relevant events for a time-to-event question. Because either event ends the interval, a result would not on its own distinguish how much of the outcome arose from progression versus death. The registry does not provide those component counts for the primary endpoint.

What can a confidence interval and a test answer?

In general, a confidence interval around a group contrast indicates the range of effect sizes that remain compatible with the data and analysis assumptions. A statistical test addresses a specified null hypothesis under its assumptions. Neither a confidence interval nor a p-value establishes clinical importance by itself. Interpretation also depends on the outcome definition, direction of the contrast, and plausible effects. No primary endpoint contrast, confidence interval, or p-value is reported in this registry record, so none can be interpreted.

How should planning illustrations be read?

The record describes sample-size illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; for time-to-event illustrations, the stated calculation concerns total events. Such calculations are planning illustrations, not observed evidence and not the trial's own design justification. They do not indicate the probability that a reported result is true. The record does not report the trial's sample-size justification, and the observed primary effect needed to interpret an effect-based illustration is not reported in the registry record.

What statistical details remain unknown?

The record lists no analysis entries. It does not report the primary analysis method, a test statistic, a p-value, missing-data procedures, censoring rules, subgroup methods, interim-analysis boundaries, or multiplicity adjustments. Those are not details that can be reconstructed from the endpoint definition or study status. Without results and methods, a statistical reader can describe the planned comparison and endpoint but cannot verify the analysis or quantify its uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists progression-free survival as the primary outcome and names objective response rate, overall survival, and patient-reported outcomes as secondary outcomes. It also reports four outcome measures, but no analysis entries. The record does not describe whether or how statistical testing across outcomes, time points, or repeated looks at the data was controlled. Multiplicity procedures, including any hierarchy or adjustment, are not reported in the registry record. No correction or testing strategy should be inferred from the list of outcomes.

The primary endpoint timeframe refers to assessment through an interim-analysis cutoff at 25 months. This wording identifies a cutoff but does not explain whether formal interim efficacy testing occurred, what rules governed any such testing, or whether the cutoff was set in advance. Those details are not reported in the registry record. The study's listed completion status does not answer those statistical questions.

The primary population is described as all patients randomized onto the study by the cutoff date. This is a population description, not a complete account of the analysis set. The record does not report whether all randomized participants were included in the primary analysis, how protocol deviations were handled, or how missing assessments and loss to follow-up were treated. It also does not report the extent of missing primary-outcome data. These omissions limit assessment of potential bias and reproducibility. Without those details and the endpoint results, the registry record supports description of the intended comparison but not an independent appraisal of its analysis.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (6.3%), sepsis (5.3%), embolism (4.8%), fatigue (4.8%), wound infection (3.2%).

The registry lists serious adverse-event figures by arm. For TRC105 plus Votrient, serious adverse events affected 27 of 63 participants at risk; for Votrient, they affected 12 of 57 participants at risk. The record separately lists deaths as 23 and 20, respectively. It does not define the relationship between those death counts and the adverse-event reporting period, nor does it state whether the deaths were attributed to treatment. The counts should therefore be read as registry-reported figures, not as evidence of cause.

The most frequently listed serious-event terms are Disease Progression (6.3%), Sepsis (5.3%), Embolism (4.8%), Fatigue (4.8%), Wound infection (3.2%), and Pyrexia (1.8%). These entries describe reported serious-event terms; they do not establish that a study drug caused an event. The registry record does not provide event-level details, timing, severity distributions, or an adjusted comparison of safety between arms.

Adverse-event counts are descriptive and can be affected by duration of exposure, ascertainment, and the reporting rules used. Those details are not reported in the registry record. A difference in raw counts should not be treated as a causal contrast without appropriate definitions and analysis. The safety information also does not answer the primary progression-free survival question.

12. What the Result Does, and Does Not, Mean

The registry record gives a clear outline of the clinical question: a randomized comparison of weekly intravenous TRC105 plus daily oral Votrient against daily oral Votrient alone in patients with advanced angiosarcoma not suitable for surgery intended to cure. It defines progression-free survival from randomization to progression or death and describes progression criteria based on RECIST v1.1. This allows readers to understand the intended endpoint and comparison.

What the record does not provide is the primary outcome result. There are no group estimates, confidence intervals, event counts, or statistical comparison results. Therefore, the record cannot show how the groups differed in progression-free survival, how uncertain an estimated difference might be, or whether any difference would be clinically important. The trial's completed status and recorded enrollment do not replace those missing estimates.

In general, a randomized design can help support a comparison of assigned groups, while an unmasked design and incomplete reporting can leave important questions about outcome assessment and analysis. The registry says progression was determined by independent radiology review, but additional review procedures and analysis details are not reported. Missing-data handling, the primary analysis method, and multiplicity procedures are also not reported in the registry record.

The serious adverse-event figures give descriptive counts and listed terms, but they do not establish treatment causation or provide a complete safety comparison. The record does not report enough detail to assess exposure duration or attribution. These figures should be kept separate from the absent primary endpoint result.

Overall, the posted information supports a description of the design, treatment arms, endpoint, and some safety reporting. It does not support a conclusion that either regimen improved, worsened, or left unchanged progression-free survival, nor does it establish a causal safety difference. Those questions require results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial poses a comparative question in a defined population with advanced angiosarcoma: whether adding TRC105 to Votrient changes progression-free survival relative to Votrient alone. Randomization and a parallel-group design are important statistical features because they frame a direct comparison between assigned regimens. The endpoint also has explicit event criteria and a stated time origin, which are necessary for interpreting a time-to-event outcome.

The case also illustrates why an endpoint definition is not the same as an endpoint result. The registry specifies progression-free survival in months, a 95% confidence interval, a RECIST v1.1 progression definition, and a cutoff. Yet it does not report estimates or a comparison. Without these, neither the magnitude nor precision of the primary contrast can be evaluated. A completed trial record can therefore remain insufficient for statistical interpretation of its main question.

Another statistical distinction is between evidence about efficacy and descriptive safety reporting. The serious adverse-event counts and event terms provide some safety information, but they do not substitute for the primary endpoint analysis and do not establish causation. Counts without fuller context about exposure, follow-up, and attribution are limited for comparing risks.

Finally, the record names several secondary outcomes and references an interim-analysis cutoff, but it does not describe multiplicity control or interim-testing procedures. Such choices can affect interpretation of statistical evidence and should be reported alongside results. The study is therefore informative as a design record, while the absence of analysis results and key methods limits what can be concluded from this registry entry.

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 this trial from the registry record is that the primary endpoint results are not reported. The record supplies the endpoint definition and summary type but not arm-specific means, confidence intervals, event counts, or a between-group comparison. It also lists no analysis entries. This prevents assessment of effect magnitude, uncertainty, or statistical evidence.

Important analysis details are also absent. The registry record does not report the primary statistical method, censoring rules, missing-data approach, protocol-deviation handling, or the precise analysis population used. Although the endpoint population is described as all patients randomized by the cutoff, the record does not confirm how that population was implemented in the analysis. The presence of an interim-analysis cutoff does not disclose whether formal interim testing occurred or how it was handled.

The trial was unmasked. The record notes independent radiology review for progression, but it does not give further details about the review process or whether reviewers were masked to assignment. This limits assessment of possible influence of treatment knowledge on endpoint ascertainment. Randomization helps frame a fair comparison in general but does not resolve reporting gaps.

Safety information is also incomplete for comparative interpretation. Serious-event counts, deaths, and selected serious-event terms are listed, but definitions, exposure duration, attribution, and detailed event-level data are not reported in the registry record. The selected terms should not be treated as a complete account of safety.

The registry records 128 enrolled and marks the study completed, but the record does not report the rationale for the enrollment target or detailed statistical design assumptions. Its effect-based planning illustrations are not a substitute for that rationale or for observed outcome results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma — NCT02979899.
• Registry record last updated 2020-05-12; status last verified 2020-05.
• Results first posted 2020-05-12.
• 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.

18. Record Summary

NCT02979899 is a completed randomized phase 3 parallel-group trial of TRC105 plus Votrient versus Votrient alone in advanced angiosarcoma. The registry records enrollment of 128, no masking, and an endpoint population defined as all patients randomized by the interim-analysis cutoff. The primary outcome is progression-free survival in months, measured from randomization to documented progression or death from any cause, with progression defined using RECIST v1.1.

The combination arm received weekly intravenous TRC105 and daily oral Votrient; the comparator received daily oral Votrient. The record lists secondary outcomes for objective response, overall survival, and patient-reported outcomes. It also includes serious adverse-event counts and selected event terms.

Primary endpoint estimates and analysis results are not reported in the registry record. The statistical analysis method, missing-data procedures, and multiplicity approach are also not reported. The available entry therefore describes the trial question and design but does not permit evaluation of the primary comparison.