This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy (NCT00574587), a na phase 1, phase 2 study. The primary outcome is Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00574587 |
| Phase | Phase 1, Phase 2 |
| Condition | Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 55 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Albert Einstein College of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Participants had locally advanced breast cancer. The registry describes three strata: HER2-positive disease, triple-negative disease, and ER-positive, HER2-negative disease. The registry record reports an enrollment of 55.
Intervention
The study regimen combined vorinostat with weekly paclitaxel, with trastuzumab for HER2-positive disease. This was followed by doxorubicin-cyclophosphamide and then surgery. Vorinostat dosing was the central question in the Phase I dose-finding component.
Comparator
The study used a single-group model and did not have a randomized control group. The dose levels and disease strata are not a like-for-like control comparison. Therefore, the record does not support a randomized comparison of the regimen against another treatment.
Primary question
The primary outcome was the recommended Phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab. The registry states that dose-limiting toxicity in cycle 1 informed this dose determination, over a timeframe of 3 weeks, and that the determination used Stratum A and B participants only. The numerical recommended dose is not reported in the registry record.
3. Trial Design
This completed study was registered as a Phase I-II trial in locally advanced breast cancer. Its model was single group, with allocation recorded as not applicable and masking recorded as none. Enrollment was 55. The study began in 2007-12, and primary completion was recorded as 2014-05.
The regimen began with vorinostat on days 1-3 and weekly paclitaxel for 12 weeks. Trastuzumab was included for HER2-positive disease. The regimen was then followed by doxorubicin-cyclophosphamide every 2 weeks for 4 cycles, followed by surgery. The registry describes strata for HER2-positive disease, triple-negative disease, and ER-positive, HER2-negative disease.
The Phase I-II design addressed dose selection as well as the intended evaluation of the regimen. The primary outcome concerned the recommended Phase II dose of vorinostat and dose-limiting toxicity in cycle 1. The registry specifies that the dose determination included Stratum A and B participants only. It does not report the detailed dose-escalation rules, stopping criteria, or protocol for moving between dose levels.
There was no randomized comparator. Consequently, the disease strata and dose-level groups should not be treated as randomized treatment arms. Differences between their posted counts cannot establish comparative treatment effects. The registry lists a secondary outcome of pathological complete response rate in participants with HER2/neu-positive locally advanced breast cancer. Its result is 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.
Before assignment: Patients with HER2 positive disease also received trastuzumab.
Overall Study
| Stage | Stratum A (HER2-positive): Dose Level 1 | Stratum A (HER2-positive): Dose Level 2 | Stratum B: Triple Negative | Stratum C: ER-Positive, HER2-negative |
|---|---|---|---|---|
| STARTED | 3 | 23 | 16 | 13 |
| COMPLETED | 3 | 23 | 16 | 13 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The recommended Phase II Dose of vorinostat was determined in Stratum A and B participants only.
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.
| Characteristic | Unit | Stratum A (HER2-positive): Dose Level 1 | Stratum A (HER2-positive): Dose Level 2 | Stratum B: Triple Negative | Stratum C: ER-Positive, HER2-Negative | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 3 | 23 | 16 | 13 | 55 | |
| Age, Continuous | years | 54 (30 to 69) | 54 (30 to 69) | 48 (41 to 64) | 46 (30 to 73) | 52 (30 to 73) |
| Sex: Female, Male: Female | Participants | 3 | 23 | 16 | 13 | 55 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended Phase II Dose of Vorinostat in Combination With Weekly Paclitaxel/Trastuzumab, measured over 3 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the recommended Phase II dose of vorinostat in combination with weekly paclitaxel/trastuzumab. It is recorded as a numerical dose in mg. The associated description says dose-limiting toxicity in cycle 1, with a timeframe of 3 weeks, and limits the dose determination to Stratum A and B participants.
In a dose-finding study, a recommended dose is a treatment-selection result: it identifies a dose intended for later evaluation, based on the dose-limiting toxicity information specified by the study. It is distinct from a measure of tumor response or a comparison of survival between treatment groups. That distinction matters when interpreting the endpoint: it addresses dose selection, not whether the regimen improves a clinical outcome.
The registry record does not report the numerical recommended dose, the count of dose-limiting toxicities used to reach it, or the decision rule used to select it. The available record therefore describes what the primary outcome was intended to measure but does not allow the dose-selection result itself to be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, single-group Phase I-II study with an enrollment of 55. Its primary outcome was the recommended Phase II dose of vorinostat with weekly paclitaxel/trastuzumab, based on dose-limiting toxicity in cycle 1 and a 3 weeks timeframe. The registry record does not report the selected dose or the primary outcome result. Thus, the central dose-finding result cannot be quantified or independently interpreted from this record.
The listed secondary outcome is pathological complete response rate in participants with HER2/neu-positive locally advanced breast cancer. The outcome result is not reported in the registry record. No response estimate, uncertainty interval, or analysis details are available in the registry record described for this trial. The study purpose includes asking whether vorinostat enhances the effectiveness of standard chemotherapy, with or without trastuzumab, but the stated purpose is not itself evidence that enhancement occurred.
The design also limits what can be concluded from any within-study group counts. There was no randomized control group, and the record explicitly identifies the arms as not a like-for-like control comparison. Comparisons across dose levels or disease strata may reflect differences in participant characteristics, treatment exposure, or other features; the record does not establish that such groups were exchangeable. The posted counts should therefore be read descriptively, not as estimates of a causal treatment contrast.
Safety counts are reported by stratum or dose level, including serious adverse events, other adverse events, and deaths. These counts describe what the registry lists for each group. They do not, by themselves, establish that an event was caused by a particular drug, and the record does not provide a randomized comparison for attributing differences. The listed percentages for selected serious event terms also lack a reported denominator in the registry record.
The most defensible interpretation is consequently narrow: the registry documents the trial’s intent, design, endpoint definition, and selected safety counts, but does not provide the primary dose result or secondary response result. Precision cannot be judged for those efficacy or dose-selection outcomes without their estimates and associated uncertainty. The absence of a reported result in this record should not be mistaken for a result of zero or for evidence about treatment effectiveness.
9. Statistical Methods Explained
The main statistical issue is that this study combines dose finding with a later-phase treatment question, while using a single-group design. Those features determine what the reported outcomes can answer and what remains uncertain. The registry record does not report a full statistical analysis plan.
Dose finding and the primary outcome
Dose-finding studies use observed toxicity information to guide selection of a dose for further study. The registry defines the primary outcome as the recommended Phase II dose of vorinostat with weekly paclitaxel/trastuzumab, in mg. It identifies dose-limiting toxicity in cycle 1 and a 3 weeks timeframe. This makes the outcome a dose-selection measure, rather than a direct measure of tumor response or long-term clinical benefit.
The registry says that only Stratum A and B participants contributed to the recommended-dose determination. Stratum A is described as HER2-positive, and Stratum B as triple negative. Stratum C is described as ER-positive, HER2-negative. The record does not state why Stratum C was excluded from the dose determination, so no reason should be inferred. It also does not report the detailed toxicity definition, escalation or de-escalation rules, cohort decision thresholds, or the numerical result.
Single-group design and comparison
A single-group study can describe outcomes among enrolled participants, but it does not create a randomized counterfactual group. Randomization is a method for making treatment groups comparable on average; this study did not use randomized allocation. Its dose levels and disease strata are not like-for-like controls. Any difference in posted counts across these groups is descriptive and may reflect group composition or other differences, not solely dose or treatment effects.
The registry describes a regimen of vorinostat and weekly paclitaxel, with trastuzumab for HER2-positive disease, followed by doxorubicin-cyclophosphamide and surgery. Since treatment components vary by HER2 status and the study includes different strata, a pooled interpretation would require a defined analysis and population. Such details are not reported in the registry record.
Outcome estimates and uncertainty
An estimate describes the observed value of an outcome in the analyzed participants. A confidence interval is a statistical range that conveys uncertainty around an estimate under the assumptions of the analysis. A narrow interval generally indicates greater precision than a wide interval, but an interval does not remove bias from study design or missing data. The primary dose estimate and an uncertainty interval are not reported in the registry record. The secondary pathological complete response outcome is listed, but its result and uncertainty are also not reported.
The registry lists 2 outcome measures and 1 analysis. Those counts do not identify the analysis model, the analysis population for each outcome, or whether adjustment was used. The detailed statistical plan, including any interim analyses, is not reported in the registry record. It is therefore not possible to determine from these registry entries how estimates were calculated or how uncertainty was handled.
Over-dispersion and count outcomes
As a general statistical point, count outcomes can vary more than a simple model assumes. This is called over-dispersion. If present, it can make standard errors too small under a model that assumes less variability, leading to intervals that are too narrow and significance tests that are too optimistic. This is a general consideration, not a claim that over-dispersion occurred in this trial. The record does not report a count model or a diagnostic assessment.
For the safety data, counts are presented by group for participants at risk and participants affected. These are useful descriptive quantities, but the record does not specify the statistical model, exposure adjustment, or methods for handling recurrent events. The listed serious-event terms are percentages, yet the denominator and derivation for those percentages are not reported in the registry record. They should not be reinterpreted as event counts or as comparative risk estimates.
Planning illustrations
General sample-size illustrations depend on assumptions about the target effect, significance level, allocation, and statistical approximation. The registry entries describe a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event outcomes, the stated planning quantity is total events; for other outcomes, it is participants per arm. These assumptions describe an illustration, not the trial’s own design justification or an observed power calculation. No planning sample-size outputs are reported in the registry record details, and such illustrations cannot replace the missing outcome estimates.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and 1 analysis, including the primary recommended Phase II dose and a secondary pathological complete response rate in HER2/neu-positive locally advanced breast cancer. The record does not provide results for either outcome. It also does not report whether the analysis involved multiple comparisons, which hypotheses were tested together, or whether any adjustment for multiplicity was planned or used.
Multiplicity arises when several outcomes, subgroups, time points, or statistical tests are examined. Repeated testing can increase the chance of a result that appears notable by chance. Adjustment methods can address some forms of this issue, but whether an adjustment is appropriate depends on the study questions and analysis plan. No specific approach should be attributed to this trial based on the registry record.
The analysis populations are not fully described. For the primary dose determination, the record specifies Stratum A and B participants only. It does not state the analysis population for the secondary outcome or provide participant flow by outcome. Although safety groups include counts at risk and affected, the record does not define the population or exposure period underlying every safety entry.
Missing-data methods, the amount of missing outcome data, and reasons for missingness are not reported in the registry record. The treatment of participants who did not complete the planned regimen or undergo surgery is also not reported. Without these details, readers cannot assess whether available outcome data represent all enrolled participants or how incomplete observations may affect the results. These omissions are especially relevant because neither the primary nor the listed secondary result is reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Stratum A (HER2-positive): Dose Level 1 | 0 | 3 | 0.0% |
| Stratum A (HER2-positive): Dose Level 2 | 2 | 23 | 8.7% |
| Stratum B: Triple Negative | 1 | 16 | 6.2% |
| Stratum C: ER-Positive, HER2-negative | 0 | 13 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Stratum A (HER2-positive): Dose Level 1 | 0 of 3 |
| Stratum A (HER2-positive): Dose Level 2 | 1 of 23 |
| Stratum B: Triple Negative | 1 of 16 |
| Stratum C: ER-Positive, HER2-negative | 0 of 13 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Stratum A (HER2-positive): Dose Level 1 | 0 of 3 |
| Stratum A (HER2-positive): Dose Level 2 | 0 of 23 |
| Stratum B: Triple Negative | 0 of 16 |
| Stratum C: ER-Positive, HER2-negative | 0 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | Stratum A (HER2-positive): Dose Level 1 | Stratum A (HER2-positive): Dose Level 2 | Stratum B: Triple Negative | Stratum C: ER-Positive, HER2-negative |
|---|---|---|---|---|---|
| pulmonary emobolism | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 1 of 23 | 0 of 16 | 0 of 13 |
| cardiac tamponade | Cardiac disorders | 0 of 3 | 0 of 23 | 1 of 16 | 0 of 13 |
| congestive heart failure | Cardiac disorders | 0 of 3 | 1 of 23 | 0 of 16 | 0 of 13 |
Serious events with the highest arm-level rate: cardiac tamponade (6.2%), pulmonary emobolism (4.3%), congestive heart failure (4.3%).
The registry lists serious adverse event counts by group. For Stratum A (HER2-positive): Dose Level 1, 3 participants were at risk and 0 were affected by serious adverse events; deaths were 0. For Stratum A (HER2-positive): Dose Level 2, 23 were at risk and 2 were affected; deaths were 1. For Stratum B: Triple Negative, 16 were at risk and 1 was affected; deaths were 1. For Stratum C: ER-Positive, HER2-negative, 13 were at risk and 0 were affected; deaths were 0. Other adverse events affected 0 participants in each listed group.
These are descriptive group counts, not estimates from a randomized safety comparison. The record does not establish that a death or adverse event was caused by a study drug. It lists cardiac tamponade at 6.2%, pulmonary emobolism at 4.3%, and congestive heart failure at 4.3% among the top serious-event terms. The denominator and event-count basis for those percentages are not reported in the registry record, so they cannot be compared directly with the group counts from the information available.
12. What the Result Does, and Does Not, Mean
The record documents an investigation of vorinostat alongside chemotherapy for locally advanced breast cancer. The regimen included weekly paclitaxel, trastuzumab for HER2-positive disease, subsequent doxorubicin-cyclophosphamide, and surgery. The study’s primary question concerned selecting a recommended Phase II dose using dose-limiting toxicity in cycle 1. Its stated purpose also included assessing whether vorinostat enhanced the effectiveness of the chemotherapy regimen, but that purpose should not be confused with a reported finding.
The primary dose result is not reported in the registry record. The listed secondary pathological complete response rate is also not reported. As a result, the record does not establish what dose was selected or what response rate was observed. It does not provide the estimates and uncertainty needed to assess the precision of those outcomes.
The study was single group, not a randomized comparison. It therefore cannot, through randomized between-group evidence, isolate the effect of adding vorinostat. Disease strata and dose levels are not substitutes for a randomized control group. The registry explicitly cautions that the arms are not a like-for-like control comparison.
The posted safety counts describe serious and other adverse events, as well as deaths, in the listed groups. They do not alone identify causality or provide a controlled estimate of comparative safety. The registry record also does not give the detailed analysis methods, missing-data handling, or full analysis populations needed to resolve those issues.
Accordingly, the trial record supports a description of the research question, regimen, design, endpoint definition, and selected safety counts. It does not support a conclusion about whether the regimen is effective, whether vorinostat enhanced chemotherapy, or whether outcomes differed because of treatment. A missing registry result is not evidence that the outcome was absent or that there was no effect.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between choosing a dose and evaluating a treatment effect. Its primary outcome was a recommended Phase II dose, tied to dose-limiting toxicity in cycle 1, rather than a direct comparison of tumor response between randomized groups. Dose-finding answers a development question: what dose should be considered for further study under the study’s approach? It does not by itself establish comparative effectiveness.
The design also illustrates why group labels need careful interpretation. The record includes dose levels and disease strata, but uses a single-group model and no randomized allocation. These groups cannot be read as equivalent treatment arms. A difference in outcomes across them would not, on its own, identify the cause of that difference.
For biostatistical interpretation, the missing primary and secondary results are consequential. The record defines what investigators intended to measure, but without the observed estimates and their uncertainty, readers cannot assess the magnitude or precision of the dose-selection or response findings. A completed status does not supply those missing estimates.
The safety entries show another important distinction: descriptive event counts are not the same as comparative risk estimates or causal attribution. The listed group counts and selected serious-event percentages offer limited descriptive information, while the lack of denominators for the term percentages and the absence of a randomized comparator constrain interpretation.
Overall, the record is informative about the study’s structure and questions, but it does not provide the results needed to answer its central efficacy question. Keeping design, endpoint, and result separate helps prevent a stated trial purpose from being mistaken for evidence of an observed treatment effect.
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 registry record does not report the numerical recommended Phase II dose, despite defining that dose as the primary outcome. It also does not report the result for the listed pathological complete response outcome. This prevents interpretation of the primary dose-selection result and the secondary response finding from the record.
The study was single group, with allocation recorded as not applicable and no masking. There was no randomized control group, and the registry notes that the arms are not a like-for-like control comparison. Thus, any descriptive differences by dose level or disease stratum cannot be interpreted as randomized treatment effects.
The record does not report dose-escalation rules, the detailed definition of dose-limiting toxicity, criteria for selecting the recommended dose, or the observed toxicity information underlying that decision. It states that Stratum A and B participants contributed to the primary dose determination, but does not explain the exclusion of Stratum C from that determination.
Statistical analysis details are limited. The analysis model, uncertainty estimates, outcome-specific analysis populations, interim-analysis approach, and missing-data methods are not reported in the registry record. The safety term percentages are listed without their denominators in the registry record described, and the record does not establish causality for the reported events or deaths. These limitations restrict both the interpretation of safety patterns and the ability to assess the precision and robustness of the study’s results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trial for Locally Advanced Breast Cancer Using Vorinostat Plus Chemotherapy — NCT00574587.
- Registry record last updated 2020-10-14; status last verified 2020-09.
- Results first posted 2020-09-18.
- 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.
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18. Record Summary
NCT00574587 is a completed Phase I-II, single-group trial of vorinostat with weekly paclitaxel, with trastuzumab for HER2-positive disease, followed by doxorubicin-cyclophosphamide and surgery in locally advanced breast cancer. Enrollment was 55. The primary outcome was the recommended Phase II dose, based on dose-limiting toxicity in cycle 1 over a 3 weeks timeframe, with Stratum A and B participants used for the determination.
The registry lists pathological complete response rate in HER2/neu-positive locally advanced breast cancer as a secondary outcome. Neither the primary dose result nor the secondary outcome result is reported in the registry record. Safety counts are listed by group, but the single-group design does not support randomized comparisons, and the record does not establish event causality.