Trebananib in Treating Patients With Advanced Angiosarcoma That Cannot Be Removed by Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trebananib in Treating Patients With Advanced Angiosarcoma That Cannot Be Removed by Surgery (NCT01623869), a na phase 2 study. The primary outcome is Confirmed Response Rate (CR or PR) Using RECIST.

2. Clinical Question

3. Trial Design

This was a phase II study of trebananib for advanced angiosarcoma that could not be removed by surgery. It was a single-group, unmasked study, with allocation recorded as not applicable. There was no control arm. The sponsor was the National Cancer Institute (NCI), and the registry record lists enrollment of 16 participants. The study status is completed; the recorded start was 2012-07 and primary completion was 2014-09.

The treatment group received trebananib at 30 mg/kg by intravenous infusion over 30-60 minutes on days 1, 8, 15, and 22. Courses were scheduled to repeat every 28 days unless disease progression or unacceptable toxicity occurred. Laboratory biomarker analysis is also listed, but further details about its role or results are not reported in the registry record.

A single-group design can describe outcomes observed among people who received the treatment, but it does not directly compare those outcomes with a concurrent untreated or alternative-treatment group. Thus, a response rate from this design would be a description of observed responses under the study’s eligibility, assessment, and follow-up conditions. It would not by itself establish what would have happened to comparable participants under another treatment or without trebananib.

The registry lists progression-free survival and overall survival as secondary outcomes. Their definitions, numerical results, and analysis details are not reported in the registry record. The available primary endpoint description concerns confirmed response using RECIST, with assessment every 8 weeks and a subsequent 4 week assessment to confirm a response. Other design details, including eligibility criteria beyond the stated disease context, treatment exposure, and follow-up completeness, 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

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 Confirmed Response Rate (CR or PR) Using RECIST, measured over Up to 18 months.

The primary endpoint is the confirmed response rate, defined as the percentage of participants with a complete response (CR) or partial response (PR) using RECIST version 1.1. It is intended to capture measurable tumor response rather than time until progression or survival. The registry describes an assessment schedule of every 8 weeks and requires a subsequent 4 week assessment to confirm a response. The stated timeframe is up to 18 months.

Under the stated RECIST criteria, a CR requires disappearance of all target and non-target lesions, and target lesions and non-target lymph nodes must meet the specified short-axis threshold of <1.0 cm. A PR requires at least a 30% decrease from baseline in the specified combined measurements, with one or more non-target lesions or non-target lymph nodes persisting. A response therefore depends on measured disease changes and the stated confirmation process, not simply on an initial scan impression.

The registry defines the rate as the number of patients with CR or PR divided by the number of eligible patients with at least one post-baseline assessment. This denominator is not necessarily identical to enrollment. The endpoint can summarize tumor shrinkage observed during follow-up, while leaving other questions—such as durability, progression, survival, and comparison with another treatment—to separate outcomes or study designs. The numerical response result and its confidence interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary response outcome at the participant level: each eligible participant is classified according to whether a confirmed CR or PR was recorded. The registry expresses the endpoint as a percentage of participants. In general, a binary percentage describes the fraction of people in the specified analysis denominator who meet a defined event or response condition. The response condition and denominator need to be read together, because changing either changes the meaning of the reported percentage.

For this endpoint, the registry defines the denominator as eligible participants who had at least one post-baseline assessment. It defines the numerator as patients with CR or PR. A participant without a post-baseline assessment is not automatically treated as a non-responder under that stated denominator. The number of eligible participants with an assessment, and the resulting response count, are not reported in the registry record. It is therefore not possible to reconstruct the response percentage from the enrollment figure alone.

The registry specifies RECIST version 1.1 as the assessment framework. In general, standardized response criteria aim to make tumor-response classifications more consistent by defining how lesions are measured and what degree of change qualifies. Here, a complete response requires disappearance of target and non-target lesions, with target lesions and non-target lymph nodes also meeting a short-axis requirement of <1.0 cm. A partial response requires at least a 30% decrease from baseline in the stated measurements, while one or more non-target lesions or non-target lymph nodes persist. These definitions distinguish response categories from other possible disease-status outcomes.

Response assessments were scheduled every 8 weeks, and a subsequent 4 week assessment was required to confirm a response. Confirmation is intended to avoid classifying a transient or unverified change as a confirmed response. The registry does not report how many participants had assessments at each time, whether any assessments were missed, or how incomplete follow-up was handled beyond defining the response denominator. The endpoint timeframe is up to 18 months; this does not establish that every participant was followed for that entire period.

The response estimate was to be accompanied by a 95% confidence interval using the method of Duffy and Santner. In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of its method. It is not a guarantee that the true value lies in the interval, and it does not correct for limitations such as the absence of a comparator or incomplete outcome reporting. With a binary response endpoint, interval width is influenced by the amount of information in the response data. The registry does not report the response estimate or interval, so neither the observed precision nor the interval’s location can be assessed.

The study is listed as single-group, with no masking and allocation recorded as not applicable. In general, a single-group study can estimate the frequency of an outcome in the enrolled and assessed group, but it cannot make a randomized comparison between treatment strategies. Without a concurrent control group, the observed response rate does not isolate the effect of treatment from other explanations. Masking can also affect some aspects of assessment or reporting; the record states that masking was none, but does not describe additional measures to reduce assessment bias.

The registry lists progression-free survival and overall survival as secondary outcomes. Time-to-event outcomes generally concern the time until a defined event, and their analysis requires information about event times and censoring. The registry does not report definitions, estimates, confidence intervals, or analysis methods for these outcomes. The primary response endpoint should therefore not be treated as a substitute for progression-free or overall survival.

A separate set of sample-size illustrations uses a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect; for time-to-event outcomes, the illustration is expressed as a total number of events, while other outcomes are expressed as participants per arm for 80% power or another stated power level. These are planning illustrations, not the trial’s reported design justification and not observed power. The registry record does not report that this trial was randomized between two arms, and its actual design is single-group. The planning assumptions therefore should not be confused with the study’s enrolled group or with an observed treatment comparison. Any additional protocol rationale, sample-size justification, or statistical analysis plan is not reported in the registry record.

Finally, no analysis records are listed for the outcome data. General statistical interpretation requires the numerical estimate, denominator, uncertainty interval, and details of the analysis population. Here, the endpoint definition is available, but those outcome results are not. Statistical methods can clarify what a reported estimate would mean, but cannot supply a missing result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment (Trebananib)")
n      <- c(16)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Trebananib)  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies confirmed response rate as the primary outcome and lists progression-free survival and overall survival as secondary outcomes. It does not report a multiplicity strategy, such as an adjustment or a prespecified hierarchy for interpreting several outcomes. Whether or how multiple outcomes were accounted for is not reported in the registry record. No analysis records are listed.

The primary endpoint description defines its denominator as eligible participants with at least one post-baseline assessment. This indicates that the endpoint is not simply described using everyone enrolled, but the number meeting the eligibility and assessment requirements is not reported. The registry does not state how participants with missing assessments, incomplete follow-up, or unconfirmed responses were handled beyond the stated denominator and confirmation requirement. The actual extent of missing outcome data is not reported in the registry record.

The analysis population is likewise not fully characterized. The record does not report whether all enrolled participants were included in any other outcome analysis, nor does it describe an intention-to-treat population or a per-protocol population. The response denominator rule should not be assumed to define populations used for the secondary outcomes, whose analysis details are not reported. The registry also does not report a statistical analysis plan, interim-analysis plan, or details of any sensitivity analyses. These omissions limit assessment of the impact of missing data, outcome selection, and analysis choices on the reported findings.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (12.5%), thromboembolic event (12.5%), cardiac arrest (6.2%), wound infection (6.2%), activated partial thromboplastin time prolonged (6.2%).

The registry lists 16 participants at risk for serious adverse events and records serious adverse events affecting 6. It also lists 16 participants at risk for other adverse events and records other adverse events affecting 12. These are counts within the trebananib treatment group; there is no comparator group in this study. The counts alone do not establish whether events were caused by treatment, and the registry record does not report event timing, duration, or individual participant histories.

The registry lists the following serious adverse event terms and percentages: dyspnea, 12.5%; thromboembolic event, 12.5%; cardiac arrest, 6.2%; wound infection, 6.2%; activated partial thromboplastin time prolonged, 6.2%; and hypocalcemia, 6.2%. They are selected terms, not a complete account of all safety information. The record does not clarify the event-level detail needed to determine whether a participant had more than one event or to assess the context of each event. Deaths are not reported in the registry record; the empty death entry should not be interpreted as a count of zero.

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

The registry record establishes that this was a completed phase II, single-group study of trebananib in advanced angiosarcoma that could not be removed by surgery. It documents the treatment schedule, RECIST-based confirmed response endpoint, planned assessment timing, and selected adverse-event counts. These details describe how the study was organized and what outcomes it intended to measure.

The primary response result itself is not reported in the registry record. There is no reported number of participants with a confirmed CR or PR, percentage, or 95% confidence interval. Consequently, the record does not establish the frequency of confirmed response in the endpoint population or how precisely that frequency was estimated. A treatment effect cannot be inferred from the fact that the endpoint was specified or that the study was completed.

Even if the observed response estimate were available, a single-group study would describe outcomes among participants receiving trebananib rather than compare treatment strategies under randomized conditions. In general, an uncontrolled response rate cannot show what response would have occurred in a comparable group receiving another treatment or no treatment. It also cannot by itself answer questions about survival, durability, or comparative safety.

The safety counts give descriptive information for the treated group, but do not establish causal attribution or relative risk compared with another group. The listed serious event terms and percentages are not a substitute for complete safety follow-up or a comparative safety analysis. The record does not report death information as a numerical count.

Accordingly, the appropriate reading is limited: the design and endpoint are described, selected safety data are recorded, and the primary numerical response result is unavailable in the registry record. This is not evidence that responses did or did not occur. It is also not a basis for medical advice or for concluding that trebananib does or does not work.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between defining an outcome and reporting its result. The registry gives a detailed confirmed-response definition, a denominator rule, and a confidence-interval method. Those details clarify what a response estimate would represent and what assessment process was intended. Yet without the response count, percentage, and interval, readers cannot evaluate the magnitude or precision of the primary endpoint.

The single-group design also illustrates why design determines the scope of inference. A percentage can describe outcomes in a treated cohort, but a comparator is needed for a direct treatment-group contrast. Without one, observed outcomes cannot distinguish a treatment-associated effect from other influences. This is a general interpretation issue for uncontrolled studies, not a claim about what happened to participants in this trial.

The record further illustrates how an endpoint population can differ from the enrolled group. The primary response denominator is defined by eligibility and the presence of at least one post-baseline assessment. Since that denominator is not reported, enrollment alone cannot establish the analysis population or reproduce the response calculation. Clear reporting of counts and missing-data handling is essential for assessing an endpoint.

Finally, selected safety counts can be read descriptively but do not provide a comparative assessment. The distinction between serious and other adverse events, the event-term percentages, and the absence of a reported death count all matter when describing the record. Overall, the trial emphasizes that design, endpoint definitions, analysis populations, and complete outcome reporting jointly determine what statistical conclusions are supportable.

15. 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 are specific to the information recorded for this study. It used a single-group design, with no comparator and no masking. Thus, any outcomes would be descriptive of the treatment group, without a randomized comparison. The registry record also does not report the numerical primary endpoint result or its 95% confidence interval, preventing assessment of response magnitude and precision.

The enrolled population is recorded as 16, while the response endpoint denominator is defined by eligibility and at least one post-baseline assessment. The number meeting that denominator rule is not reported. The record does not give participant characteristics that would help readers judge how closely the enrolled group represents the stated population, nor does it report the amount or handling of missing follow-up beyond the denominator definition.

The registry specifies RECIST assessments every 8 weeks and a 4 week confirmation assessment, but does not report assessment completion or response classification counts. The endpoint timeframe is up to 18 months; actual follow-up duration by participant is not reported. Secondary outcome details and results for progression-free survival and overall survival are also not reported in the registry record.

Safety information is limited to aggregate counts and selected serious event terms. Event timing, duration, overlap, causal assessment, and numerical death information are not reported. The record also does not report the statistical analysis plan, multiplicity approach, sample-size justification, or analysis populations beyond the primary endpoint denominator rule. These gaps limit independent assessment of the completeness and robustness of the findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trebananib in Treating Patients With Advanced Angiosarcoma That Cannot Be Removed by Surgery — NCT01623869.
• Registry record last updated 2015-10-19; status last verified 2015-06.
• Results first posted 2015-07-02.
• 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.

19. Record Summary

The registry describes a completed phase II study of trebananib in advanced angiosarcoma that could not be removed by surgery. It was a single-group, unmasked study with enrollment of 16 participants. Trebananib was administered intravenously on days 1, 8, 15, and 22 in repeating 28-day courses, subject to disease progression or unacceptable toxicity.

The primary outcome was confirmed CR or PR under RECIST, expressed as a percentage of eligible participants with at least one post-baseline assessment. The response was to be assessed every 8 weeks and confirmed with a subsequent 4 week assessment. The numerical response result and confidence interval are not reported in the registry record. Progression-free survival and overall survival are listed as secondary outcomes, but their results are not reported.

The safety record reports serious adverse events affecting 6 participants and other adverse events affecting 12, each among 16 at risk. Selected serious event terms and percentages are listed; death information is not reported. Because there was no comparator, the record supports description of the study design and recorded outcomes, not a randomized treatment comparison.