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 Re-expression of ER in Triple Negative Breast Cancers (NCT01194908), a na phase 1, phase 2 study. The primary outcome is To Determine the Maximum Tolerated Dose of Decitabine and LBH589 Given in Combination in Patients With Metastatic or Locally Advanced Metastatic Breast Cancers.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01194908 |
| Phase | Phase 1, Phase 2 |
| Condition | Breast Cancer, Breast Tumors, Breast Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with triple negative metastatic breast cancer were the intended population. The primary outcome description also refers to patients with metastatic or locally advanced metastatic breast cancers. The registry record describes triple negative disease as not expressing estrogen receptor, progesterone receptor or HER2.
Intervention
The intervention was decitabine and LBH589, drugs intended to reactivate estrogen receptor expression. The registry describes tamoxifen as a potential subsequent treatment if estrogen receptor was reactivated. The arm description identifies patients treated with decitabine and LBH589; whether tamoxifen was administered is not reported in the registry record.
Comparator
This was a single-group study, with no comparator group identified. The registry lists allocation as not applicable and masking as none. The study therefore does not provide a like-for-like comparison between the intervention and another treatment or control condition.
Primary question
The stated primary objective was to determine the maximum tolerated dose of decitabine and LBH589 given in combination. The broader study rationale was to assess whether estrogen receptor could be reactivated and, if so, whether tamoxifen could decrease cancer growth. The registry record says no data were analyzed for the primary outcome, so it does not provide an estimate addressing that question.
3. Trial Design
NCT01194908 is recorded as a Phase I/II trial sponsored by Emory University. It was a single-group, unmasked study with allocation listed as not applicable. The registry identifies one arm: patients treated with decitabine and LBH589. Although the intervention listing names tamoxifen as well, the study summary describes tamoxifen as a possible treatment after estrogen receptor reactivation. The record does not establish whether participants received tamoxifen.
The intended population was patients with triple negative metastatic breast cancer. The registry's primary outcome description also includes metastatic or locally advanced metastatic breast cancers. The study rationale was that estrogen receptor might be present but silenced in some triple negative cancers, and that decitabine and LBH589 might reactivate it. The researchers then intended to determine whether tamoxifen could decrease cancer growth if reactivation occurred. These are stated aims and rationale, not findings from analyzed participant data.
Enrollment was 5. The recorded start was 2010-07, and primary completion was 2014-01. The trial status is terminated. The reason for termination is not reported in the registry record. No randomized comparison is available, and the single-group structure does not isolate the effects of the drugs from other explanations for any observed change. In addition, the registry reports no analyzed primary outcome data. Details such as the planned dose-escalation procedure, treatment duration, eligibility criteria beyond the described cancer population, and reasons for stopping 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
| Stage | Arm A |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: No data were analyzed due to trial termination.
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 | Arm A |
|---|---|---|
| Participants analysed | 5 | |
| Age, Customized: 30-39 years | participants | 1 |
| Age, Customized: 40-49 years | participants | 2 |
| Age, Customized: 50-59 years | participants | 2 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 5 |
6. Primary Endpoint
The registry lists the primary outcome as To Determine the Maximum Tolerated Dose of Decitabine and LBH589 Given in Combination in Patients With Metastatic or Locally Advanced Metastatic Breast Cancers, measured over Estrogen receptor status checked 5 days after treatment. Staging is done every 8 weeks..
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was intended to determine the maximum tolerated dose of decitabine and LBH589 given in combination. A maximum tolerated dose is a dose-finding endpoint: in general, it is used in early-phase research to identify a dose level that can be taken forward while considering treatment-related toxicity. It is not an endpoint that directly measures whether a treatment controls cancer or improves a patient-centered outcome.
The registry's timeframe says estrogen receptor status was checked 5 days after treatment and staging was done every 8 weeks. Those monitoring details do not replace the stated primary endpoint, and the record does not report analyzed endpoint values. It states that no data were analyzed due to trial termination. The endpoint's unit, parameter, and dispersion are not reported in the registry record. The record also does not describe the dose-limiting toxicity definition, the rules used to choose a dose, or how the maximum tolerated dose would be calculated.
In general, dose-finding results depend on the observed safety experience at each dose and on how doses are assigned. Without analyzed participant data or the trial's dose-selection rules, the intended endpoint cannot be reconstructed from the registry entry. No maximum tolerated dose estimate can be inferred from enrollment or the safety entries alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical feature is that the registry reports no analyzed primary outcome data because the trial was terminated. There is therefore no reported maximum tolerated dose estimate and no reported analysis of whether estrogen receptor was reactivated. The registry's scientific rationale also included a possible subsequent role for tamoxifen, but no analyzed result about cancer growth or tamoxifen is reported. The absence of an analyzed result is not evidence for or against the proposed biological effect.
The study enrolled 5 participants and used a single-group design. Without a comparator group, the design cannot make a direct treatment-versus-control estimate. Even if outcome changes had been reported, a single-group result would need to be interpreted as a description of the enrolled participants, not as a randomized estimate of treatment effect. For this record, the primary outcome is explicitly reported as unanalyzed, so there is no such estimate to interpret.
The safety entries describe a limited set of counts: in Arm A, 5 participants were at risk for serious adverse events and 4 were recorded as affected; 5 were at risk for other adverse events and 0 were recorded as affected. The top serious adverse event term is Death at 80.0%. A separate death count is not reported in the registry record. The record does not supply further detail about event timing, severity grading, relatedness, or how the term-level percentage was defined. These entries should be read as registry safety reporting, not as a complete causal assessment.
Precision is also constrained. With enrollment of 5 and no analyzed primary outcome, the registry cannot support a stable estimate of a dose-response pattern or the frequency of less common events. A confidence interval, in general, expresses uncertainty around an estimate; no primary endpoint estimate or interval is reported. The registry provides no statistical analysis results, and the number of analyses is recorded as 0. Statistical significance, effect size, and uncertainty for the primary question are therefore not available.
Termination is an important part of the interpretation, but its reason is not reported in the registry record. It should not be attributed to toxicity, lack of activity, recruitment, or any other cause without documentation. The posted record supports conclusions about the study's stated aims, design, enrollment, status, and reported safety counts; it does not support a conclusion about efficacy or an identified tolerable dose.
9. Statistical Methods Explained
The registry describes a Phase I/II, single-group study. In general, an early-phase dose-finding study asks how participants tolerate different dose levels and uses safety information to guide dose selection. The stated primary objective was to determine the maximum tolerated dose of decitabine and LBH589 in combination. However, the dose levels, dose-escalation rules, dose-limiting toxicity criteria, and statistical dose-selection method are not reported in the registry record. Without these details, the intended statistical procedure cannot be assessed or reproduced.
What does a single-group design estimate?
In general, a single-group study describes outcomes among participants who received the study intervention. It has no concurrent control group to distinguish intervention effects from the natural course of disease, other care, or other influences. The registry lists allocation as not applicable, masking as none, and the model as single group. Its arm description names patients treated with decitabine and LBH589. The registry does not identify a like-for-like control comparison. It is therefore important not to treat the design as a randomized comparison or as a controlled estimate of benefit.
That design point is separate from whether outcomes were analyzed. The primary outcome population is explicitly described as having no data analyzed due to trial termination. The registry lists 0 analyses. Thus, even a descriptive primary-outcome estimate is unavailable in the posted record. The observed enrollment of 5 is not a substitute for an endpoint result.
How should precision be understood?
In general, an estimate is more informative when its uncertainty is made explicit. A confidence interval gives a range of values compatible with the data and analysis under its assumptions; it is not a guarantee that the true value lies in that range. The registry does not report a primary endpoint estimate, confidence interval, or other measure of precision. As a result, readers cannot assess the uncertainty of a maximum tolerated dose estimate from this record.
Small studies also tend to provide limited information about uncommon events and about patterns across dose levels. This is a general limitation, not a numerical estimate of precision for this trial. The record reports enrollment of 5 but does not provide outcome data by dose or a dose allocation description. A numerical precision calculation cannot be recovered from the listed enrollment alone.
What is the role of the monitoring schedule?
The registry says estrogen receptor status was checked 5 days after treatment and staging was done every 8 weeks. These are monitoring timeframes, not statistical analysis methods. The record does not report the assay procedure, the criteria for classifying reactivation, the timing of all assessments, or how repeated observations would be analyzed. It also does not report a statistical model for tumor staging or cancer growth.
In general, repeated measurements from one participant may be correlated; treating them as independent observations can make uncertainty appear smaller than it is. A suitable analysis would need to account for how measurements are collected and related over time. The registry record does not describe whether or how this issue would be addressed. Because no primary outcome data were analyzed, there are no repeated-measure results to evaluate in this case.
What can safety counts establish?
The registry reports participants at risk and affected for serious and other adverse events. Counts are descriptive: they show the number recorded in the categories listed, but do not by themselves establish that the intervention caused an event. In general, causal attribution requires consideration of timing, alternative causes, event definitions, and the study design. Those details are not reported in the registry record. The safety counts also do not constitute an analysis of the stated maximum tolerated dose because the dose-specific information and dose-selection rules are absent.
The record lists a planning illustration framework based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect set as a stated fraction of an observed effect. It specifies that time-to-event illustrations would use total events and other illustrations would use participants per arm. Those are general planning assumptions, not evidence of the trial's own design. The registry identifies a single-group study, reports no analyzed primary outcome, and provides no observed effect for a planning illustration to use. A sample-size illustration cannot be interpreted as observed power or as a result from this trial. The trial's own sample-size justification and statistical plan are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures and identifies the primary objective as determining the maximum tolerated dose of decitabine and LBH589. It also lists a secondary objective concerning the safety of tamoxifen in combination with decitabine and LBH589. The record does not provide the full outcome definitions, analysis methods, or results for the secondary objective. The specific treatment sequence and whether tamoxifen was given are not reported in the registry record.
Multiplicity concerns arise in general when several outcomes, treatment contrasts, time points, or subgroup analyses are tested. If many hypotheses are examined, the chance of a false-positive finding can increase unless the analysis plan accounts for that. Here, the registry reports 0 analyses and no primary outcome data analyzed. It does not report a multiplicity adjustment strategy, a hierarchy of outcome tests, or planned subgroup analyses. There are no reported hypothesis-test results for which a multiplicity adjustment can be evaluated.
The primary outcome population is described as having no data analyzed due to trial termination. The registry does not report an analysis population definition, such as who would be included in a safety or dose-finding analysis, nor does it describe how participants with missing assessments would be handled. The amount, timing, and reasons for missing outcome data are not reported in the registry record. In general, missing data can affect an estimate when the likelihood of missingness is related to participant status or outcome; assessing that possibility requires information about which observations are missing and why.
Enrollment was 5, but the record does not state how many participants had each planned assessment or whether all enrolled participants received study treatment. No imputation method, sensitivity analysis, or missing-data assumption is reported. The absence of analyzed primary outcome data means that no claim about the consequences of missingness or the robustness of a result can be made.
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 |
|---|---|---|---|
| Arm A | 4 | 5 | 80.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A | 0 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A |
|---|---|---|
| Death | General disorders | 4 of 5 |
Serious events with the highest arm-level rate: death (80.0%).
The registry records Arm A with 5 participants at risk for serious adverse events and 4 affected. For other adverse events, it records 5 at risk and 0 affected. These are counts as entered in the registry; they do not provide event timing, severity grades, or a causal assessment. The record's top serious adverse event term is Death at 80.0%. The denominator and the method used to calculate that percentage are not reported in the registry record. A separate count of deaths is also not reported.
The serious-event count and the term-level percentage should not be combined to infer an unreported death count. The record does not explain how the listed term relates to the affected-participant count, whether events were assessed as related to treatment, or whether multiple events could be recorded for one participant. In general, adverse event reporting describes events observed or recorded during a study; it does not by itself establish that the intervention caused them. The single-group design offers no control-group rate for comparison.
These safety entries are especially limited in scope because enrollment was 5 and the trial was terminated. The registry does not give dose-specific adverse event counts or the rules used to judge dose-limiting toxicity. The reported counts therefore cannot be used to reconstruct the maximum tolerated dose or to characterize the full safety profile of the regimen.
12. What the Result Does, and Does Not, Mean
The registry record documents an intended early-phase investigation of decitabine and LBH589 in triple negative metastatic breast cancer. Its main stated objective was to determine the maximum tolerated dose of the combination. The rationale described possible reactivation of estrogen receptor and a subsequent role for tamoxifen if reactivation occurred. Those aims explain what the study sought to investigate; they are not evidence that receptor reactivation or cancer growth reduction occurred.
The trial enrolled 5 participants and was terminated. The primary outcome entry states that no data were analyzed. Consequently, the record does not establish a maximum tolerated dose, the frequency of estrogen receptor reactivation, or a change in cancer growth. It also does not report an analyzed comparison of tamoxifen with another treatment. A statistical conclusion about efficacy, lack of efficacy, or dose-related benefit cannot be drawn from the listed information.
The record does report limited safety counts: 4 of 5 participants in Arm A were recorded as affected in the serious adverse event category, while 0 of 5 were recorded as affected for other adverse events. It lists Death at 80.0% among the top serious terms, but provides no separate death count or denominator explanation. These entries warrant careful reading as registry reporting, not as proof of causation or a complete account of events.
In general, a study's result is most useful when its endpoint, analysis population, statistical method, and uncertainty are all reported. Those details are not available for the primary endpoint in this record. Its single-group design also lacks a concurrent comparator, which limits causal interpretation even when descriptive outcomes are available. The appropriate conclusion is that the registry records the study's purpose, design, status, enrollment, and some safety information, but does not provide analyzed primary outcome evidence.
13. Why This Trial Matters Statistically
This trial illustrates a distinction between a scientific hypothesis and a statistical result. The registry presents a rationale for trying to reactivate estrogen receptor in triple negative breast cancer and then considering tamoxifen. It separately defines a primary objective focused on the maximum tolerated dose of decitabine and LBH589. Neither the biological rationale nor the treatment sequence is itself a measured result.
The record also demonstrates why early-phase study design details matter. A dose-finding conclusion depends on which doses were used, how participants were assigned to dose levels, which toxicities counted as dose-limiting, and what rule guided escalation or selection. Those methods are not reported in the registry record. The primary outcome is explicitly recorded as unanalyzed, so there is no reported dose estimate to interpret.
Another statistical lesson concerns comparison. A single-group design can describe the experience of enrolled participants, but it does not provide a concurrent control rate. In general, a control group helps separate an intervention-associated change from changes that could occur for other reasons. No such comparison is identified in this trial. The absence of analyzed primary data adds a further limit: even descriptive evidence for the primary question is unavailable.
Finally, safety counts and a term-level percentage should not be treated as interchangeable measures. The registry records 4 serious adverse event-affected participants among 5 at risk and lists Death at 80.0%, while the separate death count is not reported. Without denominator definitions and event-level context, those entries cannot support a fuller safety interpretation. This case shows why transparent outcome definitions, analysis methods, missing-data information, and reasons for termination are important for readers assessing an early-phase study.
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 record has several trial-specific limitations for statistical interpretation. It reports enrollment of 5 and a terminated status, but does not report the reason for termination. The primary outcome population is explicitly described as having no data analyzed due to termination. As a result, the central dose-finding question has no reported estimate or uncertainty measure.
The design is single group, with allocation listed as not applicable and masking as none. A comparator group is not identified. Even had descriptive outcomes been reported, the design would not provide a like-for-like controlled comparison. The registry also does not report the dose levels, assignment process across dose levels, stopping criteria, toxicity definitions, or dose-selection method needed to evaluate a maximum tolerated dose analysis.
The relationship between the listed intervention and the intended treatment sequence is not fully documented. The intervention listing includes decitabine, LBH589, and tamoxifen, while the arm description names decitabine and LBH589 and the summary describes tamoxifen as conditional on estrogen receptor reactivation. Whether tamoxifen was administered is not reported in the registry record. The timing and definitions for receptor status and staging are only partially described.
Safety reporting is also limited. The record provides at-risk and affected counts and a serious event term percentage, but not the separate death count, percentage denominator, event timing, dose-specific events, or relatedness assessments. Missing outcome data, analysis populations, statistical methods, and multiplicity procedures are not reported. These gaps prevent reconstruction of the intended analyses and restrict interpretation to the recorded design, status, enrollment, and safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Re-expression of ER in Triple Negative Breast Cancers — NCT01194908.
- Registry record last updated 2015-01-26; status last verified 2015-01.
- Results first posted 2015-01-26.
- 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.
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18. Record Summary
NCT01194908 is a Phase I/II, single-group study sponsored by Emory University, with a recorded start of 2010-07 and primary completion of 2014-01. It was terminated and enrolled 5 participants. The stated primary objective was to determine the maximum tolerated dose of decitabine and LBH589 in patients with metastatic or locally advanced metastatic breast cancers.
The registry describes a rationale involving possible estrogen receptor reactivation and subsequent tamoxifen use, but whether tamoxifen was administered is not reported. No primary outcome data were analyzed due to trial termination. The safety record lists 4 serious adverse event-affected participants among 5 at risk, 0 affected for other adverse events among 5 at risk, and Death at 80.0% among the top serious terms. A separate death count and the reason for termination are not reported in the registry record.