Study of Panobinostat in Patients With Neuroendocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Panobinostat in Patients With Neuroendocrine Tumors (NCT00985946), a na phase 2 study. The primary outcome is Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria..

2. Clinical Question

The study was intended to characterize tumor response to panobinostat and also to examine time to progression, overall survival, toxicity and tolerability, and changes in Notch 1 signaling. The registry describes response assessment every 8 weeks, up to 5 years. Participants were to be assigned a response category, including complete response, partial response, stable disease, progressive disease, several categories of early death, or unknown.

This is a descriptive question within a treated group, not a randomized comparison of panobinostat with another treatment or with no treatment. Without a concurrent control group, the study record cannot isolate the effect of treatment from the course of disease or other influences. The registry record does not report a primary response count, response rate, or analysis. Consequently, the clinical question is clear, but the posted results do not provide the endpoint result needed to quantify the observed response in this trial.

3. Trial Design

This is a phase II, single-group study sponsored by the University of Wisconsin, Madison. The condition is listed as neuroendocrine tumors, and the intervention is panobinostat (LBH589). The arm description states that all patients would take panobinostat. Enrollment is recorded as 15. The study started in 2010-05, had a primary completion date of 2015-04, and is listed as terminated.

The registry records allocation as not applicable and masking as none. These design features mean that the study does not provide a randomized, masked comparison between treatment groups. Its design can describe outcomes among participants receiving the study drug, but it cannot by itself provide the like-for-like contrast that a randomized control group is intended to support. No comparator arm is described in the record.

The primary endpoint is the number of participants in response categories determined using Response Evaluation Criteria in Solid Tumors (RECIST). Assessments were planned every 8 weeks, up to 5 years. The endpoint description says that all participants included in the study would be assessed, including those with protocol treatment deviations. It lists response categories ranging from complete response to progressive disease, as well as early death categories and unknown.

Secondary aims included toxicities, time to progression and overall survival in patients with gastrointestinal neuroendocrine tumors, and Notch 1 expression before and during treatment. The record also lists an outcome concerning the number of participants with toxicities. The reason for termination, detailed eligibility criteria, treatment schedule, and reasons for any treatment deviations are not reported in the registry record. The record does not establish why enrollment was 15 or whether that number was planned or determined by events during conduct.

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 of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria., measured over every 8 weeks, up to 5 years.

The primary endpoint is the number of participants in tumor response categories assessed using RECIST. The listed categories are complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of another cause, and unknown. The endpoint description says that a confirmed anti-tumor response would be validated by RECIST. Assessment was scheduled every 8 weeks, up to 5 years.

RECIST provides standardized criteria for classifying tumor response, helping make assessments more consistent than an informal description of whether a tumor appears to have changed. The endpoint is categorical: it distinguishes types of observed status rather than representing a continuous measurement. The registry does not state which RECIST version was used, how confirmation was operationalized, or how measurements were collected and reviewed.

The endpoint is intended to describe tumor status during the study, not to establish a causal treatment effect. In a single-group study, response categories can be reported for the treated participants, but there is no concurrent randomized group to show what would have happened under an alternative treatment. The record does not report the number of participants in any response category or a response-rate estimate. Thus, the endpoint definition is available, while its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study and a primary endpoint that counts participants in categorical tumor-response states. It does not report an analysis or statistical methods for the endpoint. The concepts below are general explanations of how such outcomes are commonly understood, not a claim about methods used in this study unless explicitly stated by the registry record.

What does a participant count represent?

A count is the number of participants assigned to a specified category. For this endpoint, categories include complete response, partial response, stable disease, progressive disease, several early-death classifications, and unknown. A count alone does not express the proportion of an assessed group in a category unless the denominator is also stated. The registry record does not report these category counts or the number assessed, so a response proportion cannot be recovered from the record.

Counts can be useful because they show how observations are distributed across clinically defined categories. They also require careful interpretation: the same count can have different implications depending on the number of participants assessed, how missing assessments are handled, and whether the population being counted matches the population named in the endpoint. The record's endpoint description says that all participants included in the study would be assessed even when protocol treatment deviations occurred. It does not report how this intention was implemented or how unknown response status was handled in any analysis.

Why is a single-group design different from a controlled comparison?

In general, a randomized controlled trial compares outcomes between groups formed by random assignment. Randomization is used to make the groups comparable, on average, with respect to factors that can affect outcome. A single-group study has no such concurrent comparison. Its observed outcomes can describe the participants in the group, but they cannot distinguish the treatment's contribution from other explanations, including disease course, participant selection, and changes in care over time. This study is listed as single-group, with allocation not applicable and masking absent. No control-group estimate is available in the registry record.

A response category observed after treatment is therefore not, by itself, a treatment-effect estimate. A treatment-effect estimate requires a defined contrast, such as the difference between outcomes under alternative assigned strategies. In this study record, no alternative arm is described. No adjusted or unadjusted treatment comparison, effect estimate, or uncertainty interval is reported.

What does a confidence interval communicate?

In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. It does not resolve limitations of design, measurement, or missing data, and it does not turn an uncontrolled observation into a randomized comparison. No confidence interval for the primary response endpoint is reported in the registry record, so its precision cannot be evaluated from the posted results.

How should the stated planning illustration be understood?

General sample-size planning asks how much information a future study might need to detect a chosen effect under stated assumptions. The planning assumptions associated with this record refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Those are planning assumptions, not evidence that this trial used a two-arm design. The actual trial is listed as a single-group study. Any sample-size figures based on those assumptions are planning illustrations, not observed power and not a retrospective assessment of the trial's ability to detect an effect.

In general, a planning result depends on the assumed effect, variability or event frequency, allocation, significance criterion, and analysis method. If an assumed effect is smaller, more information is generally needed to distinguish it from random variation. These are general relationships, not a reconstruction of this trial's design rationale. The protocol's sample-size justification and statistical plan are not reported in the registry record. No values for the planning illustrations or observed response effect are reported in the record.

Why do outcome definition and analysis population matter?

General statistical interpretation depends on a precise outcome definition and a clear population for analysis. The registry provides the response categories and states that participants with treatment deviations would still be assessed. It does not give a detailed analysis-population definition, participant flow, or rules for handling unassessed participants. An intention-to-treat analysis, for example, is a general approach that analyzes participants according to their randomized assignment; that concept does not map directly onto a study with no randomized allocation. The registry record does not identify a named analysis population.

Likewise, a stated assessment schedule does not establish how many assessments occurred for each participant or how follow-up ended. The endpoint timeframe is every 8 weeks, up to 5 years, but the record does not report the observed follow-up distribution or the timing of the last assessment. These details matter when interpreting categorical response, time to progression, and survival outcomes. No survival analysis method, censoring rule, or missing-data method is reported in the registry record.

Finally, a statistical plan would ordinarily clarify which outcomes were primary, how outcomes were summarized, what uncertainty measures were used, and whether adjustments were planned for multiple analyses. This record specifies the primary endpoint and lists additional outcomes, but does not report those analytic details. The absence of those details should be treated as missing information, not as evidence that a particular method was or was not used.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 5 outcome measures: a primary RECIST response endpoint and additional outcomes concerning toxicities, time to progression, Notch 1 expression, and overall survival. Testing or estimating several outcomes can raise multiplicity concerns. In general, when many hypotheses are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which results were intended to be confirmatory.

The record lists no analyses. It does not report a statistical analysis plan, hypothesis tests, confidence intervals, or methods for handling missing outcome data. Missing data can affect interpretation when participants without an observed outcome differ from those with one. General approaches may include explicit missingness rules or sensitivity analyses, but none is reported. The primary endpoint description includes an unknown category and says all included participants would be assessed despite protocol treatment deviations; it does not explain how unknown status would enter an analysis.

The record also does not define the analysis population in detail or report participant disposition. Enrollment is 15, but the number with evaluable tumor assessments is not reported in the registry record. These omissions prevent assessment of whether the intended assessment population and the population underlying any results were the same. No assumptions about interim analyses, multiplicity adjustment, missing-data handling, or analysis populations should be inferred.

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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: grade 3 diarrhea (13.3%), grade 3 pain (13.3%), grade 3 albumin, serum low (6.7%), grade 1 creatinine (6.7%), grade 3 febrile neutropenia (6.7%).

The safety record reports 6 participants with serious adverse events among 15 at risk. It separately reports other adverse events affecting 15 participants among 15 at risk. These counts describe events recorded in the panobinostat group; without a comparator group, they do not provide a comparative estimate of risk. The registry record does not report exposure time or a detailed account of event onset, duration, recurrence, or attribution.

The listed serious-event terms and percentages are Grade 3 diarrhea, 13.3%; Grade 3 pain, 13.3%; Grade 3 albumin, serum low, 6.7%; Grade 1 creatinine, 6.7%; Grade 3 febrile neutropenia, 6.7%; and Grade 1 glucose, serum-high (hyperglycemia), 6.7%. These are the terms and percentages recorded; the registry does not provide additional context in this record to explain their timing or relationship to treatment. The death count is not reported in the registry record.

Serious adverse events and other adverse events are separate summaries and should not be added together to infer a total number of affected participants. A participant may be represented in more than one event category, and the record does not give participant-level overlap. The listed safety data are descriptive and cannot establish whether panobinostat caused an event or how its safety compares with another treatment.

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

The study record describes a phase II investigation of panobinostat in patients with neuroendocrine tumors, with a RECIST-based tumor-response endpoint and additional aims related to toxicity, progression, survival, and Notch 1 expression. It also records serious and other adverse events in the treated group. These details show what the study set out to assess and what safety counts are posted.

The record does not report the primary response categories or a response-rate estimate. It therefore does not establish how many participants had complete response, partial response, stable disease, progressive disease, or another listed outcome. The number of participants assessed for response is also not reported. Without these results, the primary endpoint cannot be quantitatively interpreted from the registry record.

The study design also limits what could be inferred even if descriptive response results were available. Because there is no control group, outcomes among participants receiving panobinostat cannot by themselves establish what would have occurred under another treatment or without the study drug. The absence of a randomized comparison should not be replaced by assumptions about expected outcomes or historical benchmarks; none is reported in the registry record.

The listed safety counts are similarly descriptive. They do not establish causation, comparative safety, or a rate adjusted for time at risk. No conclusions about time to progression, overall survival, or Notch 1 expression can be drawn from the record because their results and analyses are not reported. The status is terminated, but the reason for termination is not reported, so the status alone does not explain the available results or imply why the study ended.

In short, the record supports a description of the design, intended outcomes, and recorded adverse-event counts. It does not report the efficacy outcomes or analyses needed to quantify tumor response or compare treatment strategies. The distinction between a defined research question and a reported result is central to interpreting this study.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between defining an endpoint and reporting evidence for that endpoint. The record specifies a clinically interpretable set of RECIST response categories and a planned assessment schedule. Yet it does not report category counts, an estimate of response, or an analysis. A clearly named endpoint is not itself an outcome result, and its presence should not be mistaken for evidence about the endpoint.

The single-group design also illustrates the distinction between describing outcomes and estimating comparative effects. A treated cohort can provide descriptive information, but without a concurrent control group it cannot separate treatment-associated outcomes from other influences. This is important when interpreting studies where the main question concerns whether an intervention changes outcomes, rather than merely what outcomes occurred during treatment.

Safety reporting raises a related interpretive issue. Counts of affected participants and lists of event terms can describe what was recorded, but comparison requires an appropriate reference group and clear information about ascertainment and time at risk. The registry provides some counts and event terms, but does not report exposure duration or comparative analyses. These limitations are relevant to statistical interpretation, not just to clinical judgment.

Finally, the record illustrates why analysis plans and missing-data rules matter. It identifies a primary endpoint and several additional outcomes, but does not report how those outcomes were analyzed, how multiple outcomes were handled, or how unobserved assessments were treated. Those details are needed to understand the statistical basis and precision of results. In this case, the absence of reported analyses means that the record can be read as a description of design and posted safety information, but not as a quantitative report of the primary efficacy endpoint.

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 has several limitations specific to interpretation of this trial. Although enrollment is recorded as 15, it does not report participant flow, the number who began treatment, the number assessed for tumor response, or the number included in any outcome analysis. The primary endpoint description says participants with treatment deviations would still be assessed, but does not say how many had deviations or how they were handled in practice.

The record does not give the primary response-category counts or an estimate of response. It also does not report results for time to progression, overall survival, toxicity outcomes beyond the posted adverse-event summary, or Notch 1 expression. The reason for termination is not reported. These gaps prevent interpretation of the planned efficacy outcomes and do not permit an explanation of the study's status.

Because this was a single-group study with no masking, there is no randomized control comparison in the record. The design cannot address treatment effects through a direct between-group contrast, and the record does not report methods for limiting assessment bias. Eligibility criteria, treatment dose and schedule, adherence, concomitant treatments, and detailed follow-up information are not reported in the registry record.

The registry also does not report the statistical analysis plan, a sample-size justification, missing-data rules, analysis-population definitions, or a multiplicity approach. No confidence intervals or hypothesis tests are listed. The posted safety counts lack event-level timing, exposure duration, and participant-level overlap. These omissions restrict what can be concluded from the record; they should not be filled by assumptions about the protocol or the conduct of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Panobinostat in Patients With Neuroendocrine Tumors — NCT00985946.
• Registry record last updated 2019-12-09; status last verified 2017-06.
• Results first posted 2017-07-17.
• 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

NCT00985946 is a phase II, single-group study of panobinostat (LBH589) in patients with neuroendocrine tumors, sponsored by the University of Wisconsin, Madison. Enrollment is recorded as 15. The study started in 2010-05, had a primary completion date of 2015-04, and is listed as terminated.

The primary endpoint is the number of participants in RECIST tumor-response categories, assessed every 8 weeks, up to 5 years. The record lists additional outcomes concerning toxicity, progression, survival, and Notch 1 expression. It reports serious adverse events affecting 6 participants among 15 at risk and other adverse events affecting 15 participants among 15 at risk.

The primary response result, outcome analyses, reason for termination, and detailed statistical plan are not reported in the registry record. The single-group design does not provide a randomized comparator.