Trial of LBH589 in Metastatic Thyroid Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of LBH589 in Metastatic Thyroid Cancer (NCT01013597), a na phase 2 study. The primary outcome is Tumor Response Rate to LBH589..

2. Clinical Question

The study also set out to evaluate time to progression, overall survival, toxicity, tolerability, tumor markers, and Notch1 protein expression patterns. These are distinct questions: the primary endpoint classifies tumor response, while the other outcomes concern time to events, safety, tolerability, or biological measurements. Their results are not reported in the registry record in the information.

The clinical question is limited by the study’s single-group design. A response observed in this group could describe what happened during treatment, but this design does not supply a concurrent control group for separating treatment effects from other explanations. The registry record does not report the details needed to assess participant selection or the extent to which results apply beyond those enrolled.

3. Trial Design

This is a Phase II study with a single-group model and no masking recorded. The registry identifies LBH589 as the intervention and reports an enrollment of 13. Allocation is recorded as NA; there is no randomized arm assignment or like-for-like control comparison described. The absence of a comparator is central to interpreting the results: the design can describe outcomes in the treated group, but cannot directly compare them with outcomes under another intervention.

The study summary describes LBH589 at 20 mg by mouth, three times weekly. The arm description adds no further information. Details such as treatment duration, dose interruptions, dose reductions, adherence, and rules for stopping treatment are not reported in the registry record. They should not be inferred from the stated schedule.

The primary outcome is tumor response rate, recorded as a number of participants and assessed every 8 weeks. The registry describes RECIST v.1.0 criteria for target lesions assessed by CT or MRI. Other named outcomes concern Notch1 protein expression patterns, time to progression, overall survival, tumor markers, toxicity, and tolerability. The record lists 7 outcome measures and one analysis, but the statistical analysis methods and the results for the primary and secondary outcomes are not reported in the registry record.

The study start is listed as 2010-01, primary completion as 2013-08, and status as COMPLETED. The sponsor is the University of Wisconsin, Madison. These registry entries identify the study’s administrative context; they do not by themselves establish when participants were enrolled, how long each participant was followed, or whether every planned assessment was completed. Those details are not reported in the registry record.

The posted serious and other adverse event summary is for one LBH589 group, with 13 participants at risk in each summary. The reported serious adverse event figures therefore describe safety in the study group, not a contrast between treatments. The record does not provide a randomized comparison, and the adverse event entries should not be read as a comparative treatment effect.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

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 Tumor Response Rate to LBH589., measured over Every 8 weeks..

The primary endpoint is the number of participants classified as having a tumor response to LBH589. The registry specifies assessment every 8 weeks, with target lesions evaluated by CT or MRI using RECIST v.1.0. A response includes complete response, defined as disappearance of all target lesions, or partial response, defined as a 30% or greater decrease in the sum of the longest diameters of target lesions. Stable disease and progressive disease are categorized as no response. The registry defines progressive disease as a 20% or greater increase in the relevant sum, using the smallest sum recorded since baseline as the reference, or the appearance of one or more new lesions.

Response criteria turn imaging assessments into a consistent classification. In general, a prespecified rule helps make the outcome more reproducible and makes clear which changes count as response. It also means the classification is not the same as a measure of symptoms, function, or survival. The study listed time to progression and overall survival separately, so those outcomes should not be conflated with the primary response endpoint.

The registry reports the outcome definition and assessment interval, but the observed number classified as response is not reported in the registry record. The number of participants included in the primary endpoint analysis, the handling of unevaluable assessments, and any missing imaging data are also not reported in the registry record. Enrollment of 13 does not, on its own, establish the denominator used for the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry gives an outcome definition and some design information, but it does not report a detailed statistical analysis plan. The following explains general statistical ideas relevant to reading the posted information; it does not assert that a particular method was used in this study.

What does a participant count represent?

The primary outcome is a count of participants classified as having a response. For a binary outcome, each participant is assigned to one of two broad states for the purpose of that outcome: response or no response. In general, a count can be reported alongside the number assessed, and the corresponding proportion summarizes the share of that analysis group meeting the definition. Here, the registry provides the endpoint definition but not the response count or the number assessed for the primary endpoint. No response proportion can therefore be read from the registry record.

The enrollment of 13 is the number reported as enrolled; it should not automatically be treated as the analysis denominator. In general, participants may have missing or unevaluable endpoint assessments, and analysis populations can be defined in different ways. The registry record does not describe the primary endpoint analysis population or how missing and unevaluable imaging results were handled. Neither the count of enrolled participants nor the assessment schedule resolves those unanswered questions.

How does the response definition work?

RECIST v.1.0 provides the stated classification framework for target lesions measured on CT or MRI. The registry counts complete and partial responses as response. It groups stable and progressive disease under no response for this endpoint. These categories are determined by the definitions recorded for the trial, rather than by an informal judgment that a scan looks better or worse. In general, using stated criteria can support consistent assessment, although the record does not report who assessed scans, whether assessments were independently reviewed, or how disagreements were handled.

The response outcome is assessed every 8 weeks according to the registry. In general, a repeated assessment schedule describes planned or specified observation times; it does not tell readers whether all visits occurred, how assessments outside those times were handled, or how the final response classification was derived. Those operational and analysis details are not reported in the registry record.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. A narrower interval indicates greater precision under that method’s assumptions, while a wider interval indicates less precision. For a single-group binary outcome, an interval can describe uncertainty around a response proportion, but its interpretation depends on the chosen method and analysis denominator. The registry record does not report a response estimate or confidence interval, nor does it identify an interval method. There is therefore no trial-specific interval to interpret.

A hypothesis test and a confidence interval answer related but different questions. In general, a test evaluates compatibility with a stated null hypothesis under its assumptions; an interval displays a range of plausible values for the target quantity under its method. Neither can be reconstructed without the relevant result and analysis details. Although the record lists one analysis, its test, model, significance threshold, and handling of multiplicity are not reported in the registry record.

Why does the single-group design matter?

In general, a single-group study can estimate or describe outcomes within the observed group, subject to the quality of measurement, follow-up, and analysis. It does not include a concurrent control group that would directly describe outcomes under an alternative condition. A comparison with a historical or external group would require additional information and assumptions; no such comparison is described in the registry record. It would be inappropriate to present the study as a randomized comparison.

Consequently, even if a response result were posted, it would describe the observed group under the trial’s criteria, not by itself establish the difference attributable to treatment. Factors other than the intervention can influence observed outcomes in a single group. This general limitation applies independently of whether the observed response count is large or small.

What is over-dispersion, and does it apply?

In general, over-dispersion means that observed variability is greater than a model expects. It can matter for outcomes such as counts when the model’s variance assumptions do not fit the data, because standard errors and intervals may then be too optimistic. The primary outcome is defined as a participant count, but the registry does not report a count model or any assessment of over-dispersion. It is not possible to say from the record that over-dispersion was present, assessed, or relevant to the analysis. The concept is a general statistical consideration, not a reported finding from this study.

How should the planning illustration be read?

The accompanying sample-size section is described as a planning illustration computed from an observed effect, not as the trial’s own design calculation. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The illustration reports participants per arm for 80% power in non-time-to-event settings, while time-to-event planning uses a total number of events. These are planning quantities, not observed participant counts and not observed power.

There is an important distinction between that hypothetical planning setup and this trial’s registry design. This study is recorded as single-group, with allocation NA; it is not a two-arm randomized comparison. The planning illustration should therefore not be read as the actual design or sample-size justification for this trial. The registry record does not report the study’s own sample-size justification, and the primary observed effect needed to understand such an illustration is not reported in the registry record. No extra numerical result should be inferred from the assumptions alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary tumor response outcome and several other outcome areas, including Notch1 protein expression, time to progression, overall survival, tumor markers, toxicity, and tolerability. The record reports 7 outcome measures and one analysis. The presence of several outcomes raises a general multiplicity question: when many outcomes or tests are examined, the chance of at least one apparently unusual result can increase if results are interpreted without accounting for the number of comparisons. This is a general statistical concern, not evidence that a particular adjustment was needed or performed in this study.

Whether the study used a multiplicity adjustment, designated additional outcomes as exploratory, or applied a prespecified hierarchy is not reported in the registry record. The statistical plan, exact analysis methods, and any rules for interpreting multiple outcomes are also not reported. The outcome titles do not establish which analyses were conducted or how findings were selected for reporting.

Missing data and analysis populations also affect interpretation. The registry does not report how many participants had evaluable response assessments, whether any assessments were missing, how incomplete follow-up was handled, or what population was used for each outcome. The number enrolled is 13, but it is not necessarily the number analyzed for every endpoint. The record does not describe exclusions, withdrawals, or imputation methods; these details are not reported in the registry record.

In general, missingness can affect estimates when participants with unavailable measurements differ from those with observed measurements. The direction and size of any such effect depend on the circumstances and cannot be inferred without information about missingness and the analysis. No assumptions about missing data should be attributed to this study based on the registry information.

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 serious adverse event terms

Serious events with the highest arm-level rate: death, nos (23.1%), neutrophils/granulocytes (anc/agc) (7.7%), platelets (7.7%), hemorrhage/bleeding (7.7%), colitis, infectious (7.7%).

The registry’s LBH589 safety summary lists 13 participants at risk for serious adverse events and 6 affected. For other adverse events, it lists 13 participants at risk and 0 affected. These are descriptive figures for the single study group; there is no comparator group from which to calculate a treatment contrast. The record does not report a formal comparative safety analysis.

The registry also lists serious adverse event terms with percentages: Death, NOS at 23.1%; Neutrophils/granulocytes (ANC/AGC) at 7.7%; Platelets at 7.7%; Hemorrhage/bleeding at 7.7%; Colitis, infectious at 7.7%; and CNS cerebrovascular ischemia at 7.7%. The denominator and the precise counting basis for these term percentages are not reported in the registry record. The percentages should therefore be read as entries in the posted summary, not as independently reconstructed participant counts.

In particular, Death, NOS is listed as a serious adverse event term with a percentage, while the registry’s deaths entry is null. The term and its percentage should not be converted into a death count. The record does not provide enough information to determine event timing, duration, severity beyond the serious-event classification, relatedness to LBH589, or whether one participant had more than one event. Those details are not reported in the registry record.

In general, adverse event summaries describe events observed and recorded during a study; they do not by themselves show that treatment caused an event. The single-group design also prevents a direct comparison of these figures with a control-group rate.

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

This record documents a Phase II, single-group study of LBH589 in patients with metastatic MTC or radioactive iodine resistant DTC. It identifies a RECIST v.1.0 primary response endpoint, an assessment schedule of every 8 weeks, and a posted enrollment of 13. The registry also lists secondary outcome areas and descriptive safety figures. These details allow readers to understand the intended clinical question and some features of the posted record.

The record does not report the primary response result. It therefore does not show how many participants had complete or partial response, how many had stable or progressive disease, or what response proportion was observed. It also does not report a primary endpoint confidence interval or the endpoint analysis denominator. Without these, the primary outcome’s magnitude and precision cannot be assessed from the registry record.

The design does not include a concurrent comparator. In general, a single-group result can describe what was observed among participants in that group, but cannot by itself establish what would have happened under another treatment or condition. It cannot provide a randomized estimate of the difference between LBH589 and a comparator. The registry record does not report a comparative efficacy result.

The safety summary reports 6 participants affected by serious adverse events among 13 at risk and 0 affected by other adverse events among 13 at risk, as well as serious-event term percentages. These entries are descriptive, and the record does not report a control group or the details needed to attribute events to treatment. They should not be used to infer causation or to reconstruct missing death data.

The planned outcomes extend beyond tumor response, but their results are not reported in the registry record. Nor are the detailed statistical methods, missing-data handling, or analysis populations described. Accordingly, this registry information supports a careful account of the study design, endpoint definition, and posted safety summary. It does not support a conclusion about the magnitude or precision of the primary response outcome, or a comparative conclusion about treatment effects.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the difference between an outcome definition and a posted outcome result. The registry describes a specific response classification and imaging schedule, but does not report the response count. A clearly defined endpoint is essential for interpretation, yet it cannot substitute for an estimate, its denominator, or information about uncertainty. Readers need all of these elements to judge what the observed data show and how precisely they do so.

The single-group design makes the comparison question equally important. A single group can be described, but the absence of a concurrent comparator means that the record cannot provide a randomized contrast. This distinction is especially useful when reading clinical trial reports: the design determines which statistical questions can be answered, regardless of how clearly an endpoint is defined.

The record also separates safety description from causal inference. The serious and other adverse event summaries describe affected participants in the LBH589 group. They do not estimate a difference in safety between treatments. The listed adverse event terms and percentages are useful parts of the posted summary, but their interpretation is bounded by the lack of comparator information and by the unreported denominator and event details for those percentages.

Finally, the sample-size section is a planning illustration, not evidence of achieved power or the original design rationale. Its hypothetical assumptions differ from the registry’s single-group design. Recognizing that distinction prevents a planning calculation from being mistaken for an observed result or a justification used by the investigators. More broadly, this record shows why registry interpretation depends on separating what is defined, what is observed, what is estimated, and what remains unreported.

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.

Several trial-specific limitations constrain interpretation of the registry record. First, the primary response result is not reported. Although the outcome definition and assessment schedule are available, the response count, analysis denominator, and precision estimate are not. The central endpoint therefore cannot be quantified from this record.

Second, the design is single-group, with allocation recorded as NA and no masking. There is no like-for-like control comparison. This means the record cannot show a randomized between-group difference. The absence of a comparator also applies to interpretation of the safety summary.

Third, the registry does not report the analysis population, missing-data handling, or details of the imaging assessment process. It is not possible to determine from this record whether all enrolled participants had evaluable scans, how missing assessments were treated, or how response classifications were reviewed. These gaps limit assessment of potential measurement and analysis issues.

Fourth, the statistical analysis methods and sample-size justification are not reported in the registry record. The registry lists one analysis, but does not identify the model, interval method, hypothesis test, or any multiplicity procedure. The planning illustration is explicitly separate from the trial’s own design and should not be taken as its justification or as observed power.

Finally, the serious adverse event summary gives affected counts and term percentages, but the record does not report the percentage denominators, event timing, relatedness, or a non-null death count. Results for the other planned outcomes are also not reported in the registry record. These limitations arise from what is available in this record; they should not be filled by assuming methods or results that are not documented.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial of LBH589 in Metastatic Thyroid Cancer — NCT01013597.
• Registry record last updated 2019-11-29; status last verified 2017-03.
• Results first posted 2016-07-11.
• 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 record describes NCT01013597, a Phase II, single-group study titled Trial of LBH589 in Metastatic Thyroid Cancer. Its official title specifies metastatic medullary thyroid cancer and radioactive iodine resistant differentiated thyroid cancer. The study lists LBH589, described in the summary as 20 mg by mouth three times weekly, and an enrollment of 13. The sponsor is the University of Wisconsin, Madison.

The primary endpoint is tumor response under RECIST v.1.0, assessed by CT or MRI every 8 weeks. The response result is not reported in the registry record. The posted safety summary lists 6 participants affected by serious adverse events among 13 at risk and 0 affected by other adverse events among 13 at risk. The study is recorded as completed, with start 2010-01 and primary completion 2013-08. The record does not report the detailed statistical analysis methods, endpoint analysis population, or results for the other listed outcomes.