A Study of Vorinostat and Tamoxifen in Newly Diagnosed Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Vorinostat and Tamoxifen in Newly Diagnosed Breast Cancer (NCT01194427), a na phase 2 study. The primary outcome is Changes in Markers of Proliferation Prior to and After Study Drug Administration.

2. Clinical Question

The clinical question focused on a tissue biomarker rather than a clinical outcome. The registry describes comparing tissue from the original breast biopsy with tissue obtained after treatment. It does not report a completed analysis of those changes, so the record does not establish the direction or size of any Ki-67 change.

The study was intended to examine surrogate biomarkers of response during a short pre-surgery treatment period. That framing is important: the primary question concerns a measured marker in tumor tissue, not whether treatment changes long-term outcomes. The registry lists the study as terminated and states that recruitment difficulties prevented completion. It reports two participants enrolled and no study-specific analyses or results to report.

3. Trial Design

This was a phase II, multi-institutional study of vorinostat and tamoxifen in women with newly diagnosed breast cancer. The registry classifies it as a single-group study with no masking and allocation recorded as not applicable. There was no randomized treatment comparison or like-for-like control arm. Instead, the planned comparison was within the treatment period: tissue at baseline versus tissue after the study drugs.

The arm description says vorinostat and tamoxifen were taken for about 14 days before definitive surgery. The primary endpoint description specifies oral vorinostat 400 mg once daily and tamoxifen 20mg once daily, with Ki-67 proliferation index assessed at baseline and 14 days. The study’s stated aim was to evaluate surrogate biomarkers of response during this short treatment window.

The registry reports enrollment of two participants. It states that recruitment difficulties meant the study could not be completed, and records the status as terminated. The start is listed as 2011-03 and primary completion as 2011-11. The registry record does not report the reason for termination beyond the recruitment difficulty stated in the primary outcome population description.

Because the design had a single group, the planned tissue change could not by itself distinguish treatment-related change from other sources of change over time. The record does not describe a control group, randomization, or masking. It also does not report a detailed statistical analysis plan or a sample-size justification for the trial itself. Planning illustrations associated with the posted results should therefore be distinguished from the actual design and enrollment.

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.

Before assignment: Women 18 years or older with a histologically confirmed diagnosis of invasive mammary carcinoma on a core needle biopsy and with adequate organ function who are awaiting a definitive surgical procedure or initiation of neoadjuvant chemotherapy are eligible.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Two (2) participants were enrolled; however, due to difficulty in recruitment, we were not able to complete the study. There were not study-specific analyses completed or results to report.

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 Changes in Markers of Proliferation Prior to and After Study Drug Administration, measured over Baseline and 14 days.

The primary endpoint was the percentage change in the proliferation index Ki-67 between baseline and the post-treatment biopsy, considered for ER-positive and ER-negative tumors. The stated assessment times were baseline and 14 days, following 14 days of vorinostat and tamoxifen. Ki-67 is used in this study as a marker of tumor cell proliferation; the study’s stated purpose was to examine surrogate biomarkers of response in breast cancer tissue.

In general, a biomarker endpoint can provide an early, biologically focused measure over a short observation period. It is not automatically equivalent to a clinical outcome, and a change in a marker does not by itself establish a change in how patients feel, function, or survive. The registry describes Ki-67 as the measure of interest, but does not report a completed estimate of percentage change, its uncertainty, or a test of the change.

The record contains no study-specific analyses or results to report. It therefore does not establish whether baseline and post-treatment Ki-67 values were obtained for either receptor-status group, or whether any values were usable in an analysis. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What would the primary comparison estimate?

The planned endpoint was a percentage change in Ki-67 between baseline and the post-treatment biopsy. In general, a percentage-change measure expresses a follow-up value relative to a baseline value. Its interpretation depends on how the measure is defined, how tissue measurements are obtained, and whether values are available at both time points. The registry describes the endpoint and assessment times but does not provide the calculation formula, measurement procedures, or a completed estimate.

Because the study is recorded as single-group, the planned comparison was within participants over time rather than between randomized groups. In general, repeated measurements on the same participant are related; an analysis should account for that relationship rather than treat the observations as independent. The registry does not report which method, if any, was planned or used for this endpoint. It also does not state whether the analysis would use individual changes, a group-level summary, or an adjusted model.

What would uncertainty add?

General statistical interpretation separates an estimate from its uncertainty. An estimate describes the observed size and direction of a change; a confidence interval conveys how imprecise that estimate may be under the chosen analysis. A p-value addresses compatibility with a specified null model and depends on both the data and the analysis assumptions. None of these primary endpoint statistics is reported in the registry record, so they cannot be interpreted for this study.

Small or incomplete studies can yield unstable estimates, and an analysis based on very limited observations may be highly sensitive to individual measurements. This is a general consideration, not a claim about unreported participant-level data in this trial. The registry does not report the number of evaluable biopsy pairs, the distribution of Ki-67 values, or any analysis population for the primary endpoint.

How should planning calculations be read?

General sample-size calculations describe how much information a future study might need under stated assumptions. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe the effect to detect as a stated fraction of the observed effect. For time-to-event calculations, the stated convention is a total number of events using the Schoenfeld approach; other calculations are expressed as participants per arm.

Those assumptions describe planning illustrations, not the recorded design of this trial. The actual study is classified as single-group, not a two-arm study with equal allocation. A planning calculation is not an observed power calculation: it does not show that the trial had a particular probability of detecting an effect after the data were collected. The record says no study-specific analyses or results were available, so the planning assumptions cannot be treated as a completed efficacy analysis. The registry does not report the trial’s own sample-size justification.

In general, calculations based on an observed effect can be sensitive to how that effect was estimated. If the estimate is imprecise, using it as an input may also make a planning result uncertain. No observed primary endpoint estimate is reported in the registry record, so readers should not infer one from a planning illustration or use it as evidence that the trial demonstrated an effect.

Why does over-dispersion matter in general?

Over-dispersion occurs when the variability in data is greater than a statistical model assumes. If it is ignored, standard errors may be too small and confidence intervals may be too narrow. That can make results appear more precise than the data justify. This is a general statistical issue; the registry does not report an over-dispersion assessment or identify a model for the Ki-67 endpoint. The endpoint’s scale and analysis details would be needed to determine whether this issue applied.

What methods are documented?

The record documents the endpoint description, time frame, treatment regimen, single-group design, and the lack of study-specific analyses or results. It does not report the statistical test, model, handling of repeated measurements, adjustment variables, missing-data method, or confidence-interval procedure. These should be treated as not reported in the registry record rather than inferred from the phase or endpoint description. As a result, there is no basis for reconstructing an analysis or assessing whether model assumptions were met.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint description distinguishes ER-positive and ER-negative tumors, but the registry record does not explain how those groups were to be incorporated into the analysis. It does not report whether each group was treated as a separate primary comparison, how any multiple testing would be handled, or whether an adjustment for multiplicity was planned. The statistical analysis plan is not reported in the registry record. With no study-specific analyses or results reported, there are no endpoint tests whose multiplicity adjustment can be evaluated.

The record reports two participants enrolled and says that recruitment difficulties prevented study completion. It does not give the number of participants with baseline tissue, post-treatment tissue, or complete Ki-67 measurements. It also does not describe exclusions, withdrawals, protocol deviations, or the number included in an analysis population. Those details are not reported in the registry record.

Missing-data handling is not reported. It is therefore not possible to determine whether any endpoint values were unavailable, how unavailable values would have been handled, or whether the endpoint analysis was intended to include all enrolled participants or a defined subset. The statement that no study-specific analyses or results were available should not be interpreted as proof that every planned measurement was missing; the record simply does not provide the information needed to distinguish completed measurements from unreported analyses.

Likewise, the registry does not identify an intention-to-treat, per-protocol, or other analysis population for the primary outcome. No assumptions about inclusion or missingness can be verified from the record.

11. 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 non-serious adverse event terms

The registry lists the vorinostat and tamoxifen group with two participants at risk for serious adverse events and zero participants affected by a serious adverse event. For other adverse events, it lists two participants at risk and two affected. These are participant counts, not counts of individual event episodes. The registry does not list serious adverse event terms, and it does not identify the types of other adverse events.

The deaths field has no reported value, so deaths are not reported in the registry record. A blank or unreported death count should not be read as a numerical count of zero. The adverse-event information is therefore limited to the counts recorded for the serious and other categories and the absence of listed serious-event terms.

In general, safety counts describe what was recorded among participants at risk during the study; interpretation also depends on event definitions, observation time, severity, and completeness of reporting. The registry does not provide those details for the other adverse events. With the study terminated after recruitment difficulties and no study-specific analyses reported, these counts are descriptive and do not establish a broad safety profile or answer the primary biomarker question.

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

The registry record establishes that a phase II study of vorinostat and tamoxifen was planned around short-term changes in Ki-67 in breast cancer tissue. It also establishes that the study enrolled two participants, was terminated, and reported recruitment difficulties as the reason it could not be completed. The record does not provide a completed primary endpoint analysis or results.

That distinction matters. A trial can have a clearly stated biological question without producing an estimate that answers it. Here, no percentage change in Ki-67 is reported for ER-positive or ER-negative tumors. There is therefore no reported direction, magnitude, or precision of change to interpret. The absence of a reported endpoint result does not mean the marker stayed unchanged; it means the registry does not report a study-specific analysis or result.

The planned comparison was between baseline and post-treatment tissue in a single group. Even a reported change over that interval would not, on its own, separate a treatment-associated change from changes that might occur over time for other reasons. There was no separate control group in the recorded design. The registry also does not provide details needed to assess how tissue measurements were obtained or analyzed.

The safety counts are limited to the categories and participant counts recorded in the registry. The record reports zero participants with serious adverse events among two at risk and two participants with other adverse events among two at risk; the other event terms are not reported. The record does not report a death count. These data do not compensate for the missing primary endpoint result and should not be treated as a full account of safety.

In short, the record is informative about the study’s intended question, design, enrollment, termination, and limited adverse-event counts. It does not establish whether the combination changed Ki-67 or provide a basis for judging the precision of such a change.

13. Why This Trial Matters Statistically

This study illustrates the difference between a planned biomarker question and an answerable statistical result. The protocol description identifies a specific marker, Ki-67, a baseline-to-post-treatment comparison, and an intended distinction between ER-positive and ER-negative tumors. But the registry also reports that the study was terminated after recruitment difficulties and that no study-specific analyses or results were available. Without an endpoint estimate, the central statistical question remains unanswered in the record.

It also highlights why design matters when interpreting change over time. A single-group before-and-after comparison can describe how measurements differ across the study period, but it does not provide a concurrent untreated comparison. If a change estimate were available, its interpretation would still depend on the study design and measurement methods. The registry does not report the information needed to evaluate those details.

The record is also a useful reminder that planning calculations and observed results serve different purposes. Sample-size illustrations rely on assumptions and are not evidence that an effect was observed, nor are they observed power. This distinction is particularly important when the recorded study design differs from assumptions used in a hypothetical two-arm calculation.

Finally, sparse reporting limits what can be learned from the study. Enrollment and adverse-event counts are documented, but the primary outcome, analysis population, missing-data approach, and statistical methods are not. Reporting those elements is important for judging what a study can support, even when recruitment prevents completion.

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 main limitation is that the registry reports no completed study-specific analysis or primary endpoint result. There is no Ki-67 estimate, confidence interval, or p-value to assess, and no reported result separating ER-positive from ER-negative tumors. The record therefore cannot answer the stated biomarker question.

Enrollment was two participants, and the registry says recruitment difficulties meant the study could not be completed. The record does not state how many participants had evaluable baseline and post-treatment biopsies or were included in any endpoint assessment. The analysis population and missing-data handling are not reported in the registry record.

The design was single-group, with the planned comparison between baseline and post-treatment tissue. There was no separate control group, so the design would not provide a concurrent estimate of what happened without study treatment. The registry does not report detailed tissue measurement procedures, statistical methods, or a trial-specific sample-size justification.

Safety reporting is also limited. The registry gives counts for serious and other adverse events, but does not list the terms for other events or report a numerical death count. These limitations reflect what is recorded; they do not establish that measurements, events, or analyses were absent outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Vorinostat and Tamoxifen in Newly Diagnosed Breast Cancer — NCT01194427.
• Registry record last updated 2013-05-17; status last verified 2013-05.
• Results first posted 2013-05-17.
• 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

The registry describes a phase II, single-group study of vorinostat and tamoxifen in women with newly diagnosed breast cancer. The intended treatment period was about 14 days before definitive surgery. The primary endpoint was percentage change in Ki-67 between baseline and the post-treatment biopsy, considered in ER-positive and ER-negative tumors.

The study enrolled two participants and is recorded as terminated. The registry states that recruitment difficulties prevented completion and that no study-specific analyses or results were available. It reports zero participants with serious adverse events among two at risk and two participants with other adverse events among two at risk; the terms for other events and a death count are not reported.

The record does not provide a primary endpoint estimate, statistical analysis plan, analysis population, or missing-data method. Accordingly, it documents the study’s intent and limited recorded outcomes, but does not establish a Ki-67 treatment effect.