Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (NCT00084682), a na phase 2 study. The primary outcome is Disease Control (i.e., Achievement of Complete Response, Partial Response, or Stable Disease).

2. Clinical Question

This is a question about the proportion of participants meeting a defined tumor-status criterion in a treated group. Complete response means disappearance of all target lesions. Partial response means at least a 30% decrease in the sum of the longest diameters of target lesions. Stable disease requires neither a response as the best response nor disease progression at 8 weeks. The record defines overall response separately as complete response plus partial response; stable disease is included in the broader disease-control endpoint, not in that definition of overall response.

The clinical question is not whether romidepsin performs better than another option. With no comparator group, the study can describe outcomes among its participants but cannot isolate a treatment effect from other explanations for those outcomes. The posted record also lists duration of response, time to progression, and overall survival as secondary outcomes. Their observed results are not reported in the registry record.

3. Trial Design

This was a phase II study sponsored by the National Cancer Institute (NCI), with a single-group model and no masking. Allocation is recorded as not applicable. The registry lists enrollment of 14 and status as completed. The study start is recorded as 2005-06, and primary completion as 2008-11. The record does not give further detail on the dates of individual participants’ treatment or follow-up.

The treatment group is described as receiving romidepsin, also referred to as FR901228 or depsipeptide. The planned regimen in the arm description is intravenous administration over 4 hours on days 1, 8, and 15. Courses were to repeat every 28 days while disease progression or unacceptable toxicity was absent. This describes the regimen, not the number of courses actually received by participants; that information is not reported in the registry record.

The study’s primary outcome is disease control, defined as achievement of complete response, partial response, or stable disease. The outcome description says tumor response was assessed every eight weeks using RECIST v1.0 for target lesions assessed by MRI. The primary-outcome timeframe is up to 2 years. The record also names duration of response, time to progression, and overall survival as secondary outcomes. It does not report their estimates or the methods used to analyze them.

The single-group structure is important when interpreting all outcomes. There is no concurrent control group whose outcomes could help distinguish treatment-associated changes from the natural course of disease, participant selection, or other influences. The study’s enrollment is 14, but the record does not state how many participants contributed data to each outcome or whether all enrolled participants received treatment. Those analysis-population details are not reported in the registry record.

The record does not report a sample-size justification, a prespecified statistical analysis plan, interim analyses, or further details about the trial’s design. The study’s phase and stated outcomes do not by themselves establish what methods were planned or whether the posted outcome descriptions fully capture the original protocol.

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 Disease Control (i.e., Achievement of Complete Response, Partial Response, or Stable Disease), measured over Up to 2 years.

The primary endpoint is the number of participants with disease control: complete response, partial response, or stable disease, assessed for up to 2 years. This combines tumor shrinkage with a category in which neither response nor progression has been observed according to the registry’s definitions. The endpoint therefore addresses whether participants met a defined disease-status criterion, rather than measuring tumor change as a continuous quantity.

The response categories are based on RECIST v1.0. Complete response means all target lesions disappear; partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. Stable disease is defined by the absence of a best response and the absence of progression at 8 weeks. The record says MRI was used to assess target lesions and that assessments took place every eight weeks.

Combining these categories can give a count of participants who met the study’s disease-control definition. It is not the same as counting only complete or partial responses: stable disease also qualifies. The record separately defines overall response as complete response plus partial response.

A disease-control count can be useful as a summary of tumor status under prespecified response categories. Its meaning depends on the definitions, assessment timing, and follow-up period. The registry record does not report the observed count, the number assessed, or the stated 95% confidence interval for this endpoint. Consequently, the magnitude and precision of the primary result cannot be described from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants meeting a binary classification: disease control or no disease control under the registry’s definition. A binary outcome places each assessed participant into one of two categories for that particular endpoint. The record describes the qualifying categories but does not state the observed count, the denominator used for analysis, or the resulting estimate. Those omissions prevent a numerical description of the primary result.

What does a confidence interval describe?

In general, a confidence interval expresses the statistical uncertainty around an estimate. For a proportion, it gives a range of values compatible with the observed data under the interval method’s assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The primary outcome lists a 95% confidence interval as its dispersion measure, but the numerical interval is not reported in the registry record. The interval-construction method is also not reported, so it is not possible to determine whether a particular method was used or to assess its suitability for the observed count.

For a binary endpoint in a single group, an estimate commonly summarizes the share of analyzed participants who met the definition. Its interpretation depends on both the number meeting the definition and the denominator. In a relatively small study, each participant’s classification can have a noticeable influence on the estimated proportion. This is a general statistical consideration, not a claim about the unreported disease-control result in this study.

How does the endpoint definition affect the result?

The disease-control definition combines complete response, partial response, and stable disease. These categories are not interchangeable: complete and partial response describe tumor response under RECIST criteria, whereas stable disease describes the absence of response and progression at the specified assessment. A combined endpoint can be useful when the question concerns any of those states, but it does not reveal how many participants fell into each category unless category-specific counts are reported. Those counts are not reported in the registry record.

The assessment schedule also matters. The record says response was assessed every eight weeks, and stable disease is defined with reference to 8 weeks. Assessment timing determines when a status is evaluated and may affect which category is assigned. The record does not describe how assessments that were missed, delayed, or unevaluable were treated. That handling is not reported in the registry record.

What can a single-group design estimate?

A single-group study can describe the outcomes observed in its participants. It does not supply a concurrent control outcome. General statistical interpretation therefore distinguishes a within-group estimate from a comparison of treatment strategies. Without a control group, observed disease control cannot by itself establish what would have happened to similar participants without the study treatment or under another treatment. This is a design limitation, not a calculation that can be repaired by a confidence interval.

Allocation is recorded as not applicable, and masking as none. These details indicate that the registry does not describe a randomized, masked comparison. The record does not provide additional information about how participants entered the study, whether outcome assessors were masked, or whether any analysis adjusted for participant characteristics. Such details are not reported in the registry record.

What do the planning illustrations mean?

In general, sample-size calculations are planning tools. They describe how many participants might be needed under stated assumptions about the effect to detect, the significance level, allocation, and statistical method. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the assumption concerns total events using the Schoenfeld method; other calculations are expressed as participants per arm.

These assumptions describe an illustrative calculation, not the design of this single-group trial. The record does not report that the trial used those assumptions to determine enrollment, and it does not report a sample-size justification. Planning illustrations are not observed power. Because the primary outcome estimate is not reported, the registry information does not support interpretation of an effect-based planning illustration as a measure of the trial’s ability to detect its actual result.

Other statistical features that could matter include over-dispersion, which in general means that observed variation exceeds what a model assumes. It can make standard errors too small if the model does not account for that extra variability. The endpoint is a participant count for a binary classification, but no model or analysis method is reported. There is no basis to say that over-dispersion was assessed or relevant to the sponsor’s analysis; the model and its assumptions are not reported in the registry record.

Finally, a posted estimate and a sponsor’s analysis may differ if they use different populations, adjustments, or methods. The registry record does not provide a sponsor analysis or a recalculated result for the primary endpoint. Therefore, no such comparison can be made. The numerical result and its precision remain unknown in the posted record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists disease control as the primary outcome and duration of response, time to progression, and overall survival as secondary outcomes. Considering several outcomes raises a general statistical issue: if many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. The registry record does not report whether tests were performed, whether any adjustment was planned, or how outcomes were prioritized beyond the primary and secondary labels. No multiplicity procedure is reported.

The record does not report a statistical analysis plan or detailed analysis populations. It is therefore not possible to determine whether analyses were intended for all enrolled participants, all treated participants, or a subset with evaluable assessments. The enrollment is 14, but the number contributing to each outcome is not reported in the registry record.

Missing-data handling is also not reported. The record does not explain how missing, incomplete, or unevaluable tumor assessments were classified, whether follow-up was censored for time-to-event outcomes, or how participants who stopped treatment were handled in analyses. These details can affect both the denominator and the interpretation of an estimate. No specific approach should be inferred from the endpoint definitions alone.

The record lists no analyses for the outcomes. This does not establish that no analyses were conducted; it means that analysis results and methods are not reported in the registry record. Interim analyses, stopping rules, and any prespecified treatment of multiple looks at accumulating data are likewise not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (35.7%), lung infection (21.4%), anemia (14.3%), thrombocytopenia (14.3%), anorexia (14.3%).

The safety summary is for the treatment group, with 14 participants at risk. The record lists 12 participants affected by serious adverse events and 11 affected by other adverse events. These are participant-level summary counts as recorded; the registry does not provide further detail about event counts per participant, timing, duration, or overlap between the serious and other adverse-event categories.

The listed top serious-event terms are fatigue at 35.7%, lung infection at 21.4%, and anemia, thrombocytopenia, anorexia, and vomiting at 14.3% each. These percentages are registry entries for the listed serious-event terms. They should not be combined or summed: a participant may have experienced more than one event, and the record does not specify the overlap. The record does not provide additional event-level detail that would support a more granular interpretation.

A serious adverse event is a safety classification, not proof that the treatment caused the event. The posted summary does not establish causation, and the listed terms should be read as events recorded in the study rather than as confirmed treatment effects. Deaths are not reported in the registry record; that absence of a reported value does not mean there were no deaths.

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

The record establishes that a phase II, single-group study evaluated romidepsin in patients with unresectable recurrent or metastatic squamous cell carcinoma of the head and neck. It defines disease control as complete response, partial response, or stable disease and describes the response criteria and assessment schedule. It also records selected safety summaries for the treatment group.

The posted information does not establish how many participants achieved disease control or how precise that estimate was. The observed primary-endpoint count and 95% confidence interval are not reported in the registry record. Results for the listed secondary outcomes are also not reported. As a result, no quantitative description of tumor response, duration of response, time to progression, or overall survival can be drawn from the posted outcome information.

The design also limits what any within-group result could establish. Without a comparator group, the study cannot directly quantify how outcomes differ from those under another treatment or a control condition. A within-group observation, even if available, would not by itself identify the cause of an outcome. This is a general limitation of single-group studies and does not depend on the direction of the observed result.

The safety figures describe reported events in the study group. They do not establish that treatment caused those events, and the record does not include enough detail to determine event timing, participant-level overlap, or the basis for any causal assessment. The unreported death information should not be interpreted as zero deaths.

Thus, the registry record is informative about the trial’s design, the endpoint definitions, and selected adverse-event summaries, but it is incomplete for assessing the primary efficacy outcome. It does not support a conclusion about the size of disease control, the precision of that result, or comparative treatment effects. The missing analysis details also prevent assessment of the handling of missing data, analysis populations, and multiplicity.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result need to be distinguished. The registry provides a detailed definition of disease control, including the response categories and assessment schedule, but does not report the observed count or confidence interval. Readers can understand what the study intended to measure without being able to evaluate the magnitude or precision of the result.

It also highlights the limits of a single-group design. An outcome observed in a treated group is descriptive of that group; without a concurrent comparator, it is not a direct estimate of the difference between treatment strategies. Statistical precision around a group estimate cannot remove that design limitation.

The listed enrollment of 14 makes transparent the scale of the study, while the absence of an outcome denominator leaves a further interpretive gap. A count is meaningful only alongside the population from which it was calculated and the rules used to classify participants. The registry does not report those analysis details for the primary endpoint.

Finally, the record shows why registry reporting matters beyond naming outcomes. Safety summaries are posted, but selected event terms do not by themselves describe causality or the full clinical context. The record also does not report the analysis plan, missing-data methods, or multiplicity procedures. These gaps matter because readers need methods as well as outcome definitions to assess how results were produced and how much confidence to place in them. The available record supports careful description, not a comparative efficacy conclusion.

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 most direct limitation is that the primary outcome is described but its observed result is not reported. The number achieving disease control, the analysis denominator, and the numerical 95% confidence interval are absent. The registry record therefore does not allow assessment of the endpoint’s observed magnitude or statistical precision.

The trial is single-group, with no comparator. This prevents a randomized, like-for-like comparison and limits interpretation of any within-group outcome. The record does not report whether participants received all planned treatment courses, how many were assessable at each follow-up, or how outcome assessments were handled when incomplete.

The registry lists three secondary outcomes but does not report their results. It also does not report analysis populations, missing-data methods, multiplicity procedures, an analysis plan, or interim analyses. The original sample-size justification is not reported in the registry record. These omissions leave uncertainty about how the registered outcomes were to be analyzed and how the reported enrollment relates to the intended analyses.

Safety information is limited to participant counts and selected serious-event terms with percentages. Event timing, duration, overlap, and causal attribution are not described. Deaths are not reported in the registry record, which should not be read as a report of zero deaths. These limitations are specific to the information posted for this trial and do not establish that further details are unavailable elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck — NCT00084682.
• Registry record last updated 2021-03-05; status last verified 2021-02.
• Results first posted 2015-05-19.
• 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

This completed phase II trial evaluated single-agent romidepsin, also called FR901228 or depsipeptide, in unresectable recurrent or metastatic squamous cell carcinoma of the head and neck. The National Cancer Institute (NCI) is listed as sponsor. Enrollment was 14; the study start is recorded as 2005-06 and primary completion as 2008-11. The design is single-group, allocation is not applicable, and masking is none.

The primary outcome is disease control—complete response, partial response, or stable disease—with tumor assessments described as occurring every eight weeks using RECIST v1.0 and MRI, for up to 2 years. Duration of response, time to progression, and overall survival are listed as secondary outcomes. The registry record does not report the observed primary or secondary outcome results.

The safety summary lists 12 participants affected by serious adverse events and 11 affected by other adverse events among 14 at risk. The listed top serious-event terms include fatigue, lung infection, anemia, thrombocytopenia, anorexia, and vomiting. Deaths are not reported in the registry record.