Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers (NCT01121939), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study asked whether a combination of bevacizumab, pertuzumab, and Sandostatin had measurable antitumor activity in patients with advanced neuroendocrine cancers. The registry record identifies objective response rate as the primary endpoint, assessed over 18 months. It defines objective response through complete or partial response under RECIST v1.0, with target lesions assessed by MRI or CT.

This is a within-group activity question, not a randomized comparison of the combination against another treatment or a control. Without a separate comparison group, the study design cannot directly estimate how outcomes would differ under an alternative treatment. The registry record does not report the observed objective response rate, so it does not provide a numerical answer to the primary question.

3. Trial Design

The registry identifies this as a Phase II study with a single-group model and enrollment of 43. The listed combination consists of bevacizumab, pertuzumab, and Sandostatin LAR® Depot. The record describes the treatment group as patients with advanced neuroendocrine cancers. Allocation is listed as not applicable, and masking is listed as none. No separate control arm is described.

The study status is completed. The recorded start is 2010-05, and the primary completion date is 2015-02. These dates describe the registry timeline; they do not establish how long any individual participant was followed. The primary endpoint timeframe is separately listed as 18 months.

The stated primary endpoint is objective response rate. The brief summary says that toxicity and progression-free survival would also be obtained and evaluated. The secondary outcomes listed in the registry are toxicity and safety, progression-free survival, overall survival, and disease control rate. Although the record lists five outcome measures, it reports zero analyses. The outcome result values and analysis details are not reported in the registry record.

A single-group design can describe outcomes among participants receiving the listed combination. It does not supply a concurrent control group for distinguishing treatment-associated outcomes from other influences, such as the underlying course of illness or differences among participants. The registry record does not report a protocol rationale for the design, a sample-size justification, eligibility criteria beyond the disease description, or details of treatment administration. Those design details 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

Analysis population for the primary outcome, as defined in the registry: Includes all 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.

Population: All Patients

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over 18 months.

The primary endpoint is objective response rate, expressed as the percentage of participants. The registry sets an 18-month timeframe and says the endpoint population includes all patients. Objective response is described using RECIST v1.0 criteria for target lesions assessed by MRI or CT. A complete response means disappearance of all target lesions. A partial response is defined as a >=30% decrease in the sum of the longest diameter of target lesions. Overall response is defined as complete response plus partial response.

In general, an objective response endpoint counts participants meeting prespecified criteria for tumor shrinkage. It gives a categorical summary: each participant is classified according to whether the criteria for response are met. This differs from measuring the size of change for every participant or describing how long disease control lasts. The registry record does not state additional details about confirmation of response, assessment schedules, handling of unevaluable participants, or the precise denominator used in the reported result.

The endpoint definition is present, but its observed value is not reported in the registry record. No confidence interval or inferential test for objective response is reported there either. Consequently, the registry record describes what the primary measure was intended to capture but does not provide the result needed to quantify the response rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies the study structure and endpoint definition, but it does not report the statistical analysis plan or numerical endpoint analyses. The methods can therefore be explained at the level of what the design and endpoint mean, while distinguishing those general concepts from the information actually documented.

What does a single-group design estimate?

The study is identified as single-group, with allocation listed as not applicable and masking listed as none. In general, a single-group study describes outcomes within the enrolled group. For a binary endpoint such as whether a participant meets objective response criteria, a basic summary is the proportion meeting those criteria among the participants included in the analysis. That summary is descriptive: it characterizes the observed group under the analysis definition. It is not a randomized treatment contrast because no separate comparator group is reported.

A comparison group can help distinguish outcomes associated with a treatment strategy from outcomes that might also occur without it or under another strategy. Without such a group, differences in participant characteristics, disease course, assessment, or other factors cannot be separated by a direct randomized comparison. This is a general limitation of single-group designs, not a finding about any particular participant in this study.

How is objective response defined?

The primary endpoint is objective response rate, stated as a percentage of participants. The registry names RECIST v1.0 and specifies MRI or CT assessment of target lesions. Complete response is disappearance of all target lesions; partial response is a >=30% decrease in the sum of their longest diameters; overall response combines complete and partial responses. In general, a binary response endpoint classifies participants according to whether they meet the response definition. The endpoint value depends on both the classification rules and the analysis population.

The registry says the endpoint population includes all patients, but it does not report whether all enrolled participants had an assessment, what happened when assessments were missing or unevaluable, or whether any confirmation requirement applied. These details can affect how a percentage is interpreted. The observed percentage and its denominator are not reported in the registry record.

What does precision mean?

In general, a confidence interval describes the statistical uncertainty around an estimate under specified assumptions. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not by itself establish that the estimate is free from bias, and it does not resolve the lack of a comparator in a single-group design. No confidence interval for objective response is reported in the registry record, so the precision of the primary endpoint cannot be evaluated from this entry.

For a binary endpoint, statistical methods may use different assumptions about the sampling distribution, especially when data are sparse or the sample is limited. The registry does not identify the method used to calculate an interval or conduct a test. No method should be attributed to this study based only on the endpoint definition or study phase.

What do the planning assumptions describe?

The registry's sample-size assumptions describe an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. Those are planning assumptions, not a report of the analysis performed in this single-group study. The record does not report the planning counts, the observed effect used, or a study-specific sample-size justification. A planning illustration is not observed power; it does not describe the probability that the completed study detected an effect.

In general, sample-size planning depends on a target effect, variability or event-rate assumptions, an error threshold, and the design. Changing those assumptions changes the planning result. Here, the documented equal allocation between two arms does not match the registry's single-group design, so the illustration should not be read as a description of this trial's enrollment rationale or analysis.

What analyses are documented?

The registry lists five outcome measures and zero analyses. It does not report a statistical analysis plan, test statistic, p-value, adjusted estimate, confidence interval, or numerical efficacy result. The absence of a reported analysis is not evidence that an analysis was or was not performed outside this record. It means the analytical methods and results cannot be assessed from the registry entry.

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("Typical Carcinoid", "Pancreatic Islet Cell")
n      <- c(32, 11)
events <- c(5, 2)
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  Typical Carcinoid  32  5  15.6  5.3  32.8  6.9  31.8  7.0  31.9
ARM  Pancreatic Islet Cell  11  2  18.2  2.3  51.8  5.1  47.7  5.5  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response rate as the primary outcome and names toxicity and safety, progression-free survival, overall survival, and disease control rate as secondary outcomes. These multiple outcomes raise a general multiplicity issue: when several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested separately without an adjustment or a prespecified interpretation strategy. The registry record does not report whether any multiplicity procedure, hierarchy, or other approach was planned.

The record lists five outcome measures and zero analyses. It does not provide outcome-specific analysis populations, statistical tests, confidence intervals, or p-values. Therefore, it is not possible to determine how the multiple outcomes were analyzed or how any reported result should be interpreted relative to the others. No numerical results for the secondary outcomes are reported in the registry record.

The primary endpoint population is described as including all patients. The record reports enrollment of 43, but does not state the number with an evaluable endpoint assessment or how missing, incomplete, or unevaluable assessments were handled. It does not describe imputation, exclusions, censoring rules, or sensitivity analyses. These missing-data methods are not reported in the registry record.

In general, missing outcome data can affect a percentage if participants with unavailable assessments are handled differently from those with observed assessments. The direction and extent of any effect depend on why data are missing and on the analysis method; neither is described. The record's all-patients wording identifies the stated endpoint population but is not enough to determine the practical handling of missing observations.

The registry also does not report whether analyses followed an intention-to-treat principle, a per-protocol approach, or another analysis-population definition. Accordingly, the precise population underlying any numerical endpoint estimate cannot be established from this entry.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (4.7%), vomiting (4.7%), abdominal pain (2.3%), acute kidney injury (2.3%), colonic obstruction (2.3%).

The serious adverse event summary lists 43 patients at risk and 6 affected for the all-patients group. The other adverse event summary lists 43 at risk and 42 affected. These are separate registry figures for serious and other adverse events; they should not be combined into a single count. The registry lists the following serious adverse event terms and percentages: Nausea, 4.7%; Vomiting, 4.7%; Abdominal Pain, 2.3%; Acute Kidney Injury, 2.3%; Colonic Obstruction, 2.3%; and Creatinine Increased, 2.3%.

In general, an adverse-event summary describes events reported during a study and does not by itself establish that the study treatment caused them. The registry record does not report whether participants could experience more than one listed event, how event terms were grouped, or the observation period used for these summaries. The listed percentages should therefore be read as registry-reported figures rather than as a complete account of event timing or attribution.

The serious adverse event record does not report a death count. It also does not provide a detailed breakdown of severity, relatedness, or management for the listed events. Those details are not reported in the registry record.

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

The record identifies a completed Phase II, single-group study of bevacizumab, pertuzumab, and Sandostatin in advanced neuroendocrine cancers, with objective response rate as the primary endpoint. It provides the endpoint's response criteria, the 18-month timeframe, enrollment of 43, and a summary of adverse event counts and selected serious adverse event terms. These registry entries describe the study's registered design and some safety reporting.

The record does not provide the numerical objective response rate, a confidence interval, or a test result. It also does not provide numerical results for the listed secondary outcomes. As a result, this entry cannot establish the observed magnitude or precision of the primary endpoint, nor can it support a quantitative comparison with another treatment. The lack of a comparator is especially important: the single-group design does not directly show how outcomes would differ under a separate treatment or control condition.

In general, an observed response rate is a description of outcomes in a defined group, not by itself proof that a treatment caused those outcomes. A confidence interval, when reported, helps describe statistical precision, but does not eliminate potential design limitations. Neither the primary estimate nor its uncertainty is reported, and the registry does not describe the analysis methods needed to interpret them.

The adverse event figures describe reported counts in the registry record. They do not, without further information, establish causation or provide a complete characterization of safety. The record does not report deaths or detailed event attribution, and the duration and handling of adverse event observation are not specified.

Thus, the registry entry is informative about the intended question, basic design, endpoint definition, and selected safety counts. It is not a complete statistical report of efficacy or safety findings. The numerical outcome results and several methods needed to interpret them are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a basic distinction between defining an endpoint and reporting its result. The registry specifies objective response rate, the RECIST v1.0 criteria used to define response, the imaging modalities, the stated population, and the timeframe. Those details make the intended measurement more interpretable than an endpoint label alone. However, without the number or percentage of participants who met the criteria, the principal result cannot be evaluated quantitatively.

It also illustrates why study design matters to interpretation. A single-group study can describe outcomes among its participants, but it does not provide a concurrent comparison for estimating a difference between treatment strategies. General statistical interpretation must keep that distinction clear: a response proportion and a comparative effect answer different questions.

Precision is another essential part of reading a result. A point estimate alone would not show how much uncertainty surrounds it; an interval estimate would help characterize sampling uncertainty. The registry record does not report either the primary estimate or an interval, so the degree of statistical precision is unknown from this entry.

Finally, the record makes visible the boundary between registry information and a full analysis report. It lists several outcomes and safety summaries, but does not report analysis methods or efficacy results. The sample-size assumptions describe an illustration involving two-arm planning, not the single-group design itself. Recognizing these distinctions prevents a design description or planning calculation from being mistaken for an observed treatment comparison.

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 specific to this registry entry constrain interpretation. It reports a single-group model and no separate comparator. The record therefore does not support a direct randomized comparison, and it does not report the observed objective response rate that would describe outcomes within the study group.

The endpoint definition is detailed, but key implementation details are not reported in the registry record. These include response confirmation, assessment timing and schedule, the number of participants with evaluable imaging, and handling of missing or unevaluable assessments. Although the endpoint population is stated to include all patients, the record does not explain the denominator used for an outcome calculation.

The registry reports enrollment of 43 and a completed status, but does not provide a numerical primary efficacy result, confidence interval, or test. It lists secondary outcomes without their numerical results and lists zero analyses. The statistical analysis plan, multiplicity approach, and analysis-population rules are not reported in the registry record.

The sample-size assumptions refer to equal allocation between two arms and a normal approximation, whereas the registered design is single-group. The record does not report the calculated planning counts or a study-specific sample-size justification. Those assumptions cannot be treated as a description of the completed study's analysis.

For safety, the registry gives event counts and selected serious-event percentages, but does not report a death count, event attribution, detailed severity information, or the observation period. These omissions limit what can be concluded from the safety summary. More complete protocol and results information is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers — NCT01121939.
• Registry record last updated 2016-02-05; status last verified 2016-01.
• Results first posted 2015-09-23.
• 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

NCT01121939 is a completed Phase II, single-group study of bevacizumab, pertuzumab, and Sandostatin LAR® Depot for advanced neuroendocrine cancers. Enrollment was 43; the registry lists no masking and allocation as not applicable. The recorded start is 2010-05, and primary completion is 2015-02.

The primary endpoint was objective response rate at 18 months, defined using RECIST v1.0 and MRI or CT assessment. The registry record does not report the primary endpoint result, its precision, or an analysis. Secondary outcomes include toxicity and safety, progression-free survival, overall survival, and disease control rate, but their results are not reported in the registry record. Safety figures list 6 serious adverse-event affected participants among 43 at risk and 42 other adverse-event affected participants among 43 at risk. A death count is not reported in the registry record.