Cabergoline in Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cabergoline in Metastatic Breast Cancer (NCT01730729), a na early/phase 1 study. The primary outcome is Overall Response Rate (ORR) at 2 Months.

2. Clinical Question

3. Trial Design

This was a completed, single-group study of cabergoline for metastatic breast cancer, sponsored by Northwestern University. The record lists the phase as EARLY PHASE1, while the official title calls it a pilot Phase II trial. Those descriptions are not the same phase label; the registry record does not explain the difference. Enrollment was 20 participants. The study began on 2013-02-11, and primary completion was recorded as 2015-12-15.

Participants received oral cabergoline twice weekly during weeks 1-4. The treatment description says courses repeated every 4 weeks in the absence of disease progression or unacceptable toxicity. There was no masking, and the design was not randomized. With no comparison group, the study was structured to describe outcomes among participants receiving cabergoline rather than to estimate a randomized treatment contrast.

The primary endpoint was overall response after 8 weeks, or 2 cycles. Secondary outcomes listed in the record include progression-free survival, treatment toxicity, changes in imaging measurements, changes in prolactin receptor expression, correlations between tissue prolactin biomarkers and response, and overall survival. The record lists 11 outcome measures but does not report analyses for them.

The registry identifies two participants as not evaluable for the primary objective because they did not reach the 8-week response time point. The observed response count, response rate, and details of participant flow beyond this statement are not reported in the registry record. The record also does not describe a control treatment or a planned comparison between groups.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 2 patients did not reach 8 week response time point and were determined not to be evaluable for this objective.

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 Overall Response Rate (ORR) at 2 Months, measured over After 8 weeks (2 cycles) of treament.

Overall Response Rate at 2 Months was defined as the number of participants who achieved a complete response or partial response after 8 weeks, described as 2 cycles, of therapy. Response was to be assessed with CT scan images and RECIST guidelines. A complete response means disappearance of all target lesions. A partial response means at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference.

The endpoint uses predefined imaging categories to classify tumor change at a stated assessment time. In general, this can make response assessment more consistent than an informal judgment, because the categories specify what counts as a response. The endpoint is a count, not a direct measure of how long a response lasts or whether participants live longer. The registry lists progression-free survival and overall survival separately as secondary outcomes.

The record also defines progressive disease as at least a 20% increase in the sum of longest diameters, using the smallest sum recorded since treatment began as the reference, or the appearance of one or more new lesions. Stable disease is neither enough shrinkage for partial response nor enough increase for progressive disease, using the smallest sum since treatment began as the reference. The observed primary endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among people who receive the intervention. It does not directly estimate the difference between that intervention and a control condition. Here, the record lists a single-group model, no masking, and allocation as not applicable. There is no concurrent comparator. Therefore, any observed response or safety event would need to be interpreted as an outcome in this study group, rather than as a randomized estimate of what cabergoline changed.

How is the primary endpoint classified?

The primary endpoint is a binary response classification at the participant level: a participant either meets the complete or partial response definition at the assessment or does not. The registry describes the reported endpoint measure as a count of participants. Complete response requires disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of longest diameters from baseline. The record also defines progressive disease and stable disease, making clear that response is categorized by prespecified imaging criteria rather than by a continuous measure alone.

In general, categorical endpoints can be straightforward to interpret when definitions and assessment timing are clear. They also discard some detail: a count of responders does not show the degree of change for each participant, the duration of response, or changes outside the category boundaries. The record does not include the observed count, rate, or participant-level measurements, so the classification rules can be described but not applied to a posted result.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a response proportion, it would indicate a range of values compatible with the data under the interval method used. A wider interval generally means less precision, while a narrower interval generally means greater precision. No confidence interval for the primary endpoint is reported in the registry record, and no interval method is specified there. The uncertainty around the observed response result therefore cannot be assessed from the posted record.

Why does the analysis population matter?

The record states that two participants did not reach the 8-week response time point and were determined not evaluable for the primary objective. That statement distinguishes enrollment from evaluability, but does not define the full analysis population. In general, an analysis should make clear how participants with missing or unevaluable assessments are handled, because different rules can change a response estimate. The registry does not report whether unevaluable participants were excluded, counted as nonresponders, or treated under another rule. No such rule should be assumed.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, not the original trial design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is a total number of events; for other outcomes, it is participants per arm.

Those assumptions do not match the recorded single-group design, which has no randomized two-arm comparison. Any such illustration is therefore not an observed result and should not be read as the actual sample-size justification for this study. The registry does not report the original sample-size justification. Planning calculations also do not represent observed power: they cannot establish whether the study had adequate information to detect an effect after results are known.

Why can over-dispersion matter?

In general, over-dispersion arises when outcome variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors and uncertainty intervals may be too small, making estimates appear more precise than warranted. This concept can matter for count outcomes and other outcomes with extra variability. The primary endpoint is described as a count of participants meeting a response definition, but the registry does not report a fitted model, dispersion estimate, or analysis method. There is no basis in the record to say whether over-dispersion was assessed or affected an analysis.

What can be inferred from the analysis record?

The record lists 11 outcome measures and zero analyses. It does not report statistical test results, model estimates, adjustment methods, or uncertainty intervals. In general, a prespecified analysis plan helps clarify which outcomes and methods were intended, while a reported analysis allows readers to assess estimates and their uncertainty. Neither a detailed statistical plan nor results of analyses are reported in the registry record. Consequently, the posted material supports description of the design and endpoint definitions, but not a reconstruction of the trial’s statistical findings.

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 (Cabergoline)")
n      <- c(18)
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 (Cabergoline)  18  0  0.0  0.0  18.5  -0.0  17.6  0.1  17.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary response endpoint and secondary outcomes such as progression-free survival, overall survival, toxicity, imaging changes, and prolactin-related measures. It reports zero analyses. The registry record does not describe a multiplicity strategy, such as prioritizing tests or adjusting significance thresholds when several outcomes are analyzed. In general, testing multiple outcomes can increase the chance of at least one apparently notable result arising by chance. Without reported analyses or a stated strategy, the extent to which multiplicity was addressed cannot be assessed.

For the primary endpoint, two participants did not reach the 8-week response time point and were determined not evaluable. The reason for non-evaluability, the handling of these participants in the analysis, and any other missing response data are not reported in the registry record. In general, missing outcome data can affect both the estimate and its precision, particularly if missingness is related to participants’ outcomes or treatment experience. No missing-data method is reported.

The registry does not define a complete analysis population or state whether all enrolled participants were included in each outcome analysis. It also does not report sensitivity analyses to examine assumptions about missing outcomes. The distinctions between enrollment, evaluability, and analysis inclusion therefore remain unclear beyond the statement about the two participants who did not reach the primary assessment.

12. 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 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 (10.0%), death nos (5.0%), pain (5.0%).

The adverse-event record lists 20 participants at risk for serious adverse events, with 4 affected. It also lists 20 participants at risk for other adverse events, with 20 affected, and reports 13 deaths. These are aggregate registry counts. The record’s listed serious-event terms include Dyspnea at 10.0%, Death NOS at 5.0%, and Pain at 5.0%.

These figures should not be interpreted as proof that cabergoline caused an event. The registry does not provide event timing, duration, severity details beyond the serious-event grouping, attribution to treatment, or a comparison group. The listed terms may not represent separate participants, and the record does not explain their relationship to the aggregate counts. Deaths are reported as a count, but the cause and timing are not detailed. The counts describe what the registry reports; they do not establish comparative risk or treatment causation.

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

The record establishes that a completed, single-group study evaluated cabergoline in metastatic breast cancer and specified an imaging-based response endpoint after 8 weeks, described as 2 cycles. It also records that two participants did not reach that assessment and were deemed not evaluable for the primary objective. These details describe the study question and some of the challenges in interpreting the endpoint.

The record does not report the observed overall response count or rate, and it lists no analyses. It therefore does not show how many participants had complete or partial response, how uncertain any estimate was, or whether secondary outcomes differed from any reference. An endpoint definition is not an endpoint result. Likewise, the listing of progression-free survival, overall survival, and biomarker outcomes does not establish their observed values.

Even if an outcome result were available, the single-group, unmasked design would not provide a randomized comparison. In general, outcomes observed during treatment can reflect multiple influences, and without a comparator the contribution of treatment cannot be isolated in the same way as in a randomized comparison. The registry also does not report a statistical analysis plan, participant-level data, or an account of missing-data handling.

The safety figures describe adverse events and deaths recorded in the study group. They do not, on their own, establish that treatment caused those events or permit comparison with another treatment. The record’s value is therefore primarily in documenting the study design, intervention, outcome definitions, and reported safety counts. It does not support a precise estimate of response or a comparative claim about treatment outcomes.

14. Why This Trial Matters Statistically

This study raises a focused statistical question: how should an imaging-defined response be described when a small, single-group study records a planned assessment time but does not report the response result? The registry makes the endpoint definition and assessment timing explicit, which are essential details for interpreting any response estimate. It also identifies two participants who did not reach the assessment, making evaluability a visible issue rather than an invisible assumption.

The design highlights the distinction between observing outcomes and estimating a treatment contrast. A single-group study can document what happened among participants receiving an intervention, but it lacks a concurrent control for comparison. This matters when readers are tempted to interpret response or safety counts as evidence that the intervention caused an outcome. The record’s absence of analyses further limits what can be concluded quantitatively.

The record also illustrates why endpoint definitions, analysis populations, and missing-data rules need to be considered together. A response category may be clearly defined, yet its estimated frequency depends on which participants contribute data and how unevaluable assessments are handled. Here, the registry reports the non-evaluable participants but not their treatment in an analysis.

Finally, the record lists several secondary outcomes and adverse-event counts without statistical analyses or detailed context. This is a useful reminder that planned outcomes and recorded counts are not equivalent to analyzed evidence. For statistical interpretation, clear design information is valuable, but estimates, precision measures, and analysis details are needed to assess what the observed data can support.

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.

The main limitation for interpreting the primary question is that the registry does not report the observed response count or rate. It also reports no analyses, confidence intervals, or statistical test results. As a result, the magnitude and precision of the primary outcome cannot be assessed from the registry record.

The single-group design has no concurrent comparator, and masking is listed as none. This limits causal interpretation: outcomes in the treatment group cannot be directly contrasted with outcomes under another condition. The registry does not describe a statistical model or adjustment for other factors.

Two participants did not reach the 8-week response time point and were deemed not evaluable for the primary objective. The reasons, analysis handling, and any other missing response information are not reported. The full analysis population is also not described. These gaps prevent evaluation of how missing assessments may affect the endpoint.

The record lists secondary outcomes but does not report their analyses or a multiplicity approach. It does not provide details on assessment procedures beyond the stated CT and RECIST endpoint, or report the analysis plan. The phase is listed as EARLY PHASE1, while the official title describes a pilot Phase II trial; the record does not explain this difference.

Safety interpretation is limited by aggregate counts without timing, attribution, or a comparator. The listed serious-event terms and death count cannot establish treatment causation. The registry also does not provide participant-level data, which would be needed for more detailed examination of outcome patterns and missingness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cabergoline in Metastatic Breast Cancer — NCT01730729.
• Registry record last updated 2019-09-17; status last verified 2019-09.
• Results first posted 2019-03-26.
• 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

NCT01730729 is a completed, single-group study sponsored by Northwestern University, with enrollment of 20. It evaluated oral cabergoline in metastatic breast cancer among participants described as positive for the prolactin receptor. The registry lists the phase as EARLY PHASE1; the official title calls it a pilot Phase II trial. The study began on 2013-02-11, with primary completion on 2015-12-15.

The primary endpoint was overall response after 8 weeks, or 2 cycles, defined as the count of participants with complete or partial response by CT imaging and RECIST. Two participants did not reach that assessment and were deemed not evaluable for the objective. The observed response result and statistical analyses are not reported in the registry record. The record lists secondary outcomes and aggregate adverse-event counts, but does not provide a randomized comparison or detailed statistical findings.