Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery (NCT03535506), a non-randomized phase 2 study. The primary outcome is Feasibility: Recruitment Rates.

2. Clinical Question

This is a feasibility question, not a randomized test of palbociclib against no treatment. Group B offered a comparison for planned blood and tissue studies, but its participants were not randomly assigned to treatment or control. As a result, differences between the groups could reflect how participants entered or participated in the study, as well as any treatment-related changes. The registry record does not report a formal comparative estimate for the primary endpoint.

3. Trial Design

This was a phase 2, non-randomized, parallel study sponsored by Georgetown University. The registry lists DCIS as the condition and describes two independent, unrelated study groups. Group A was planned to receive palbociclib before surgery; Group B was planned to receive no preoperative treatment and to contribute samples for translational studies. The registry lists enrollment of 17, compared with a planned total of 24 participants across the groups.

For Group A, the planned intervention was palbociclib 100mg by mouth daily for 12 days before surgery. Group B participants received no preoperative treatment. Their planned contributions included diagnostic core biopsy material, definitive surgical material, and blood samples at screening and before definitive surgery. These activities do not make the groups interchangeable controls: enrollment was not randomized, and the registry describes the groups as independent and unrelated.

The study had no masking. Its status is terminated. The listed start date is 2018-10-08, and the primary completion date is 2023-12-06. The registry attributes termination to lack of accrual. It does not report the number of participants in each group who completed the study, the reasons individual participants did not complete it, or whether the planned treatment and specimen collection were completed as intended.

The record lists four outcome measures and no analyses. A detailed statistical analysis plan, including planned methods for comparing groups, is not reported in the registry record. The recruitment endpoint is described over a timeframe of 5 years, with feasibility defined by the proportion of enrolled patients who are treated and complete the study. The available information therefore supports a description of the design and its recruitment outcome, but not a full account of how outcome data were analyzed.

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: Study was terminated due to lack of accural

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 Feasibility: Recruitment Rates, measured over 5 years.

The primary endpoint is titled “Feasibility: Recruitment Rates” and is measured as a count of participants. Its description defines feasibility in terms of the share of enrolled patients who are treated and complete the study: the approach would be considered feasible if more than 50% meet both conditions. The listed timeframe is 5 years.

This kind of endpoint addresses whether a study approach can recruit participants and carry them through the planned study activities. It is distinct from an endpoint intended to estimate a clinical treatment effect. For a preoperative feasibility study, recruitment and completion are relevant because the planned treatment has to be delivered before surgery and the study depends on participants reaching the required assessments and sample collections. That general rationale does not establish that any particular recruitment threshold is appropriate for a later study; the registry record does not report the justification for the threshold.

The record states that the study was terminated due to lack of accrual. It does not report a count of participants who were both treated and completed the study, nor a calculated recruitment rate for the endpoint. Enrollment of 17 alone does not establish whether the endpoint criterion was met, because the criterion also requires treatment and completion. A detailed endpoint result is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a non-randomized design imply?

In a randomized study, assignment by chance is intended to make the groups comparable, on average, with respect to factors that could affect outcomes. This study was non-randomized, and the registry describes the groups as independent and unrelated. Group A received preoperative palbociclib, while Group B received no preoperative treatment and contributed samples for translational work. The groups therefore should not be treated as though they were exchangeable arms in a randomized trial. Any observed difference could reflect participant selection, other group differences, or treatment, and the registry does not report an adjustment strategy to address such differences.

What does the feasibility threshold represent?

The primary endpoint is based on whether enrolled participants were treated and completed the study. The registry defines feasibility as more than 50% meeting both conditions. This is a threshold-based operational outcome, rather than a comparison of clinical outcomes between groups. To evaluate it, the number meeting the combined condition and the number enrolled must be available. Although the record reports enrollment of 17 and the reason for termination, it does not report the count completing treatment and study activities. A percentage cannot be inferred from enrollment alone.

How should counts and uncertainty be understood?

A count describes how many participants in the recorded group had an event or met a condition. Counts are useful for describing what was observed, but they do not by themselves quantify how precisely an underlying event rate is estimated. A confidence interval is a general statistical tool that expresses uncertainty around an estimate; a wider interval generally indicates less precision. No confidence intervals for the primary endpoint or adverse-event rates are reported in the registry record, so the precision of those rates cannot be assessed from the posted information.

For uncommon events and small groups, a zero observed count does not prove that the underlying event risk is zero. It means that no affected participants were recorded among those at risk in that group. The size of the group and completeness of event ascertainment matter when interpreting such a count. The registry gives the at-risk counts for the serious and other adverse-event categories, but does not report additional detail about follow-up duration, event ascertainment, or missing safety observations.

What is the role of a statistical analysis plan?

A statistical analysis plan specifies how outcomes will be summarized or compared, how missing information will be handled, and which analyses are intended to answer the study questions. The registry lists no analyses. The planned statistical methods, including any model, adjustment variables, or approach to uncertainty, are not reported in the registry record. It would therefore be inappropriate to assume that a particular test or model was used.

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it also states that the effect to detect is a stated fraction of the observed effect. These are illustration assumptions, not a reported design justification for this trial. A planning calculation based on an observed effect is not an observed power analysis and cannot replace the missing analysis plan. The registry does not report a sample-size justification for the feasibility study.

Why does multiplicity matter?

When a study examines several outcomes or makes multiple statistical comparisons, the chance of at least one apparently unusual result can rise if each result is interpreted separately. Multiplicity refers to this issue and to methods that may be used to account for it. The record lists a primary feasibility outcome and secondary outcomes on pathology, immunohistochemistry, and toxicity, but it does not report a multiplicity strategy or outcome analysis. No claim about adjusted or unadjusted statistical significance can be made from these entries.

More broadly, the registry information is sufficient to identify the feasibility question, design, planned groups, and some safety counts. It is not sufficient to reconstruct a complete statistical analysis. Explanations of confidence intervals, selection effects, and multiplicity are general statistical context, not methods documented as having been applied in this study.

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("Group A- Palbociclib Before Surgery", "Group B- No Pre-operative Treatment")
n      <- c(5, 12)
events <- c(5, 11)
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  Group A- Palbociclib Before Surgery  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Group B- No Pre-operative Treatment  12  11  91.7  61.5  99.8  64.6  98.5  64.0  98.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary feasibility endpoint and secondary outcomes covering pathologic changes, pathology changes on immunohistochemistry, and toxicity based on CTCAE. It lists four outcome measures overall and no analyses. A plan for controlling multiplicity across outcomes or comparisons is not reported in the registry record. Without such a plan and the corresponding results, the record does not establish which comparisons were intended to be confirmatory or how multiple findings would have been interpreted.

Information about missing data is also not reported in the registry record. In particular, there is no account of missing endpoint values, participant withdrawals, incomplete treatment, or how missing observations were handled. This matters for a feasibility endpoint requiring treatment and completion: incomplete information can affect whether participants can be classified as meeting the endpoint definition. The stated termination due to lack of accrual does not explain the completion status of individual participants.

The analysis populations are not reported in the registry record. The safety entries give the number at risk for each adverse-event category, but the record does not explain how those populations were defined or whether they include all enrolled participants. It also does not provide a statistical analysis plan describing exclusions, treatment of deviations, or analysis sets. These omissions limit reproducibility and make it difficult to connect the enrollment count to the endpoint and safety summaries.

The groups were not randomized, and no analysis is listed. There is consequently no reported method for addressing possible differences between participants in Group A and Group B. These limitations are separate: missing-data handling concerns incomplete observations, multiplicity concerns interpretation across several outcomes, and non-randomized assignment concerns comparability between groups. Each would require its own documented approach for a formal comparative analysis.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry records adverse events separately for Group A, which received palbociclib before surgery, and Group B, which received no preoperative treatment. For serious adverse events, 5 participants were at risk in Group A and 0 were affected; 12 were at risk in Group B and 0 were affected. For other adverse events, 5 were at risk in Group A and 5 were affected; 12 were at risk in Group B and 0 were affected. Deaths were 0 in both groups. No serious adverse event terms are listed.

These figures are counts, not estimates from a randomized comparison. The groups were non-randomized and had different numbers at risk, so the counts should not be read as evidence that one group had greater or lesser risk because of its treatment status. A zero count means no affected participants were recorded in the stated group and category; it does not establish that the underlying risk is zero. The registry record does not report detailed descriptions of the other adverse events, their severity, timing, duration, or relationship to treatment. It also does not report a statistical comparison of safety outcomes.

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

The record documents a phase 2 feasibility study of preoperative palbociclib for people with DCIS who were candidates for surgery. Its primary question concerned recruitment and completion, with feasibility defined as more than 50% of enrolled patients being treated and completing the study. The study was terminated due to lack of accrual, and enrollment was 17 against a planned total of 24.

Those details describe the study’s recruitment experience, but they do not supply the endpoint numerator needed to assess whether the threshold was reached. In particular, enrollment does not show how many participants received the planned treatment and completed the study. The registry does not report a calculated recruitment rate or detailed completion results. The primary endpoint result is therefore not reported in the registry record.

The adverse-event entries show the counts recorded among the participants listed as at risk in each group. They do not establish comparative safety or causation. Because assignment was non-randomized and the groups were independent and unrelated, differences cannot be attributed to palbociclib from these data alone. The secondary pathology and toxicity outcomes are named, but detailed results are not reported in the registry record.

The available information does not establish whether palbociclib changes pathologic findings, whether it is safe or unsafe, or whether it affects clinical outcomes. It also does not establish that the approach met or failed its stated feasibility threshold. Those conclusions would require outcome and analysis details not reported in the registry record. The appropriate interpretation is limited to the design, recruitment status, endpoint definition, and recorded safety counts.

14. Why This Trial Matters Statistically

This study illustrates why feasibility outcomes need to be read separately from treatment-effect outcomes. Recruitment and completion determine whether a planned study process can be carried out; they are not themselves evidence about whether a treatment changes disease-related outcomes. The registry’s primary endpoint combines treatment receipt with study completion, so an enrollment count alone cannot answer the endpoint question.

It also illustrates how design affects interpretation. The two groups were independent and unrelated, and allocation was non-randomized. Although one group received palbociclib and the other received no preoperative treatment, the design does not support treating them as like-for-like controls. This distinction is important whenever descriptive group results might otherwise be read as a treatment contrast.

The record also shows why denominators matter. Adverse-event counts are presented with the numbers at risk, and the groups differ in size. A count without its denominator can be misleading; even with denominators, small descriptive groups do not by themselves establish the precision of an estimated risk or support a causal conclusion. No confidence intervals or comparative analyses are reported.

Finally, a terminated study can leave an important gap between a stated endpoint definition and an interpretable endpoint result. The reason for termination is reported as lack of accrual, but the number who both received treatment and completed the study is not. That distinction keeps operational context from being mistaken for a measured endpoint result and helps prevent stronger claims than the registry supports.

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 specific limitation is incomplete reporting of the feasibility result. Although the registry defines a threshold and reports enrollment of 17, it does not give the number of participants who were treated and completed the study. The record states that the study was terminated due to lack of accrual, but does not report recruitment over time, group-specific enrollment totals, or participant completion details.

The non-randomized design and description of the groups as independent and unrelated limit comparative interpretation. The registry does not report how participants entered each group or whether any analytical method was planned to address differences between them. The safety counts should therefore remain descriptive rather than being interpreted as estimates of a treatment effect.

Safety reporting is limited to at-risk and affected counts, deaths, and the absence of listed serious adverse event terms. Detailed event descriptions and additional information on ascertainment or follow-up are not reported in the registry record. The secondary outcomes are identified, but their results are not reported. The analysis populations, handling of missing data, statistical methods, and multiplicity strategy are also not reported.

Finally, the record does not report the rationale for the feasibility threshold or a sample-size justification for the study. These gaps limit assessment of the intended precision and the interpretation of the planned design. They do not permit assumptions about why particular methods were chosen or how unreported outcomes might have turned out.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Preoperative Palbociclib in Patients With DCIS of the Breast That Are Candidates for Surgery — NCT03535506.
• Registry record last updated 2025-09-26; status last verified 2025-09.
• Results first posted 2025-09-26.
• 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

NCT03535506 is a phase 2, non-randomized, parallel study sponsored by Georgetown University, with no masking. It evaluated the feasibility of preoperative palbociclib for people with DCIS who were candidates for surgery. Group A was planned to receive palbociclib 100mg by mouth daily for 12 days before surgery; Group B received no preoperative treatment and was to contribute blood and tissue samples. The planned total enrollment was 24, and recorded enrollment was 17.

The primary endpoint concerned recruitment and completion over 5 years, with feasibility defined as more than 50% of enrolled patients treated and completing the study. The record lists the status as terminated and states that termination was due to lack of accrual. A detailed primary endpoint result and analyses are not reported in the registry record. Safety entries report no serious adverse events and no deaths in either group, alongside the recorded other adverse-event counts. The non-randomized design and limited outcome reporting do not support causal comparisons between groups.