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 FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma (NCT00104884), a na phase 2 study. The primary outcome is Proportion of Patients With Response to Depsipeptide.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00104884 |
| Phase | Phase 2 |
| Condition | Malignant Melanoma, Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ECOG-ACRIN Cancer Research Group |
| Results posted | Yes |
2. Clinical Question
Population
Patients with unresectable stage III or stage IV malignant melanoma were the intended population. The registry record reports that the trial ended early because of slow accrual, with final accrual of 4 patients. It does not give further participant characteristics in the outcome information.
Intervention
The intervention was depsipeptide, also called FR901228 in the trial title. The recorded regimen was a 4-hour IV infusion of 13 mg/m^2 weekly for 3 weeks, with the cycle repeated every 28 days until unacceptable toxicity or disease progression.
Comparator
This was a single-group trial, not a randomized comparison. No comparator arm is recorded. The study therefore does not provide a concurrent control group against which to compare response or adverse events.
Primary question
The primary question was the proportion of patients with a complete or partial response to depsipeptide, assessed using RECIST. The registry record gives the endpoint definition but says there are no plans for a formal analysis of any outcome measure. It therefore does not report a response estimate or a confidence interval.
3. Trial Design
This was a phase II, single-group trial of depsipeptide in patients with advanced malignant melanoma. The registry record identifies the intended population as patients with unresectable stage III or stage IV disease. It lists malignant melanoma and melanoma as the conditions under study.
Allocation is recorded as not applicable, and masking as none. These features fit the single-group design: the record does not describe random assignment or a control group. Consequently, there is no randomized between-group treatment contrast to interpret. Results, if they had been formally analyzed, would have described the treated group rather than estimating a comparison with a concurrent control.
The recorded treatment was a 4-hour IV infusion of 13 mg/m^2 weekly for 3 weeks. Cycles were to repeat every 28 days until unacceptable toxicity or disease progression. The registry gives no further treatment-delivery information, such as how many participants completed the planned regimen.
The study started on 2005-10-04, and primary completion is listed as 2006-05. Its status is terminated. The registry says it ended early because of slow accrual and reports final accrual of 4 patients. It does not report a formal analysis plan or a formal analysis for the outcome measure. The reason for termination is recorded, but details about the decision process are not reported in the registry record.
The sponsor is ECOG-ACRIN Cancer Research Group. The trial title refers to treating patients with unresectable stage III or stage IV malignant melanoma, while the official title describes a phase II trial of depsipeptide in advanced malignant melanoma. Those descriptions identify the disease setting and intervention, but do not establish any outcome result.
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 | Depsipeptide |
|---|---|
| STARTED | 4 |
| COMPLETED | 0 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Depsipeptide |
|---|---|
| Disease progression | 4 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated early due to slow accrual with final accrual of 4 patients. There are no plans to conduct a formal analysis for any outcome measure.
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.
Population: All enrolled patients
| Characteristic | Unit | Depsipeptide |
|---|---|---|
| Participants analysed | 4 | |
| Age, Continuous | years | 53.5 (51 to 66) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Patients With Response to Depsipeptide, measured over Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 3 years from study entry, up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the proportion of patients with a response to depsipeptide. A response is defined as either a complete response or a partial response according to RECIST. A complete response means disappearance of all target and nontarget lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions from baseline, together with persistence of one or more nontarget lesions and/or maintenance of a tumor marker level above normal limits.
A binary response endpoint classifies each assessed participant according to whether the defined response occurred. The proportion is intended to describe how often a response was observed in the trial population. As a general statistical point, this kind of endpoint can be clinically interpretable because it ties the outcome to prespecified criteria rather than an informal judgment. It also reduces a complex pattern of tumor measurements to a response classification, so details of changes that do not meet the response threshold are not captured by the proportion alone.
The registry specifies assessment every 3 months if a patient is less than 2 years from study entry, and every 6 months if a patient is 2 - 3 years from study entry, up to 3 years. However, the registry record says there are no plans to conduct a formal analysis for any outcome measure. It reports no response count, proportion, or confidence interval. Thus the endpoint definition is available, but its observed result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes what the primary outcome was intended to measure, but it does not provide an analyzed result. It reports no formal analysis for any outcome measure and lists 0 analyses. Although the endpoint is described as a percentage of participants and specifies a 95% confidence interval as its dispersion measure, no response proportion or interval is reported. The available information therefore does not establish how many participants met the response criteria or how uncertain an estimated response proportion would be.
The trial was terminated early because of slow accrual, with final accrual of 4 patients. That limited accrual is important context for reading the record: it leaves the study without a reported formal outcome analysis, and does not support a conclusion about the response rate. The record does not say whether any individual participant had a complete or partial response. Neither an absence of reported response nor the absence of a formal analysis should be interpreted as proof that responses did not occur.
The single-group design also limits what could be learned even if a response proportion had been reported. Without a concurrent control group, an observed response could be described in the treated participants, but the design would not by itself show what would have happened under another treatment or without depsipeptide. The record contains no randomized comparison and no like-for-like control arm.
Precision is likewise unavailable. In general, a confidence interval expresses the uncertainty around an estimate, with wider intervals indicating less precision and narrower intervals indicating greater precision under the method's assumptions. Since the registry record gives no estimate or confidence interval, there is no reported interval to interpret and no basis for describing the precision of the response outcome.
The status is terminated, and the registry attributes this to slow accrual. The record does not report a formal analysis for the primary endpoint, further analysis details, or a result for the endpoint. These omissions constrain interpretation; they do not establish a particular treatment effect, no effect, or a safety conclusion. The posted information supports a description of the design, endpoint, accrual, and termination, rather than a quantitative assessment of efficacy.
9. Statistical Methods Explained
The main statistical idea behind the primary endpoint is a proportion. For each participant with an assessment, the endpoint classifies response as present or absent using the stated RECIST criteria. The proportion is the share of assessed participants meeting those criteria. This is a general explanation of the endpoint type, not a calculation of the trial result: the registry record does not report the response count, denominator used for an analysis, or estimated proportion.
What does a confidence interval add?
The registry describes a 95% confidence interval as the dispersion measure for the primary outcome. In general, a confidence interval communicates the uncertainty associated with an estimated quantity under a statistical procedure. It is not a guarantee about the result for an individual participant, and it does not correct limitations in the study design or data collection. Its width depends on the amount of information available and the method used. Here, no confidence interval is reported, so its width and the precision of a response estimate cannot be assessed.
A proportion and its interval would need a defined analysis population and a clear rule for handling participants without an evaluable response assessment. Those details matter because the denominator determines how the estimate is interpreted. The registry describes final accrual of 4 patients but does not report an analyzed denominator or response count. It also states that no formal analysis is planned for any outcome measure. The record therefore does not permit reconstruction of the intended analysis.
Why does the single-group design matter?
In a single-group study, an outcome proportion describes what was observed in the treated group. General statistical interpretation distinguishes that description from a treatment comparison. A concurrent randomized comparator can help separate treatment differences from other influences, while a single-group result cannot provide that direct contrast. This trial is recorded as single group, with allocation not applicable and no masking. No comparator is reported. Even a precisely estimated proportion from such a design would not, on its own, answer how outcomes would differ under another treatment.
The response definition is based on tumor measurements and clinical criteria. Complete response requires disappearance of all target and nontarget lesions. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions from baseline, alongside the specified condition concerning nontarget lesions and/or tumor markers. Such criteria make the classification rule explicit. As a general point, categorizing measurements can aid consistent interpretation, but it also discards information about changes that do not cross the stated threshold.
How should planning illustrations be understood?
The registry's planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on a stated fraction of the observed effect; for non-time-to-event outcomes, its sample-size expression is participants per arm. Those assumptions do not describe this trial's recorded design, which is single group. The registry does not report a formal analysis or an observed effect estimate for the primary endpoint. Any planning illustration should therefore be read as hypothetical planning information, not as an observed result, evidence of power, or a feature of the trial's own design.
In general, sample-size planning asks how much information a future study might need to detect a specified effect under chosen assumptions. It cannot establish that the effect occurred in a completed study. A planning calculation based on an observed effect is especially dependent on the estimate used and the assumptions adopted; it is not a substitute for reporting the actual outcome estimate and its uncertainty. No planning output or response estimate is reported in the registry record.
Does over-dispersion apply?
Over-dispersion is a general concern when data vary more than a statistical model assumes, particularly in count or clustered-data settings. The primary endpoint is a binary response proportion, not a reported event-rate analysis. The registry does not state that an over-dispersion adjustment was used, and no formal analysis is reported. It would be inappropriate to infer a model or an adjustment from the endpoint definition alone.
Overall, the relevant methods are identifiable only at a broad level: a RECIST-defined binary response endpoint, with a 95% confidence interval specified as the intended dispersion measure. The registry record does not give an estimate, interval, analysis population, missing-data method, or formal statistical analysis. General explanations of proportion estimation and uncertainty clarify what such an analysis would mean, but cannot supply the missing trial result.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure and says that there are no plans to conduct a formal analysis for any outcome measure. It reports 0 analyses. A multiplicity procedure, such as an adjustment for testing several outcomes or comparisons, is not reported in the registry record. With no formal outcome analysis described, there is no reported multiplicity approach to evaluate. It would be inappropriate to infer that multiplicity was or was not addressed in an unreported analysis.
Missing-data handling is not reported in the registry record. The record does not describe how participants without a response assessment, incomplete follow-up, or other unavailable outcome information would be handled. It also does not state whether every accrued participant was assessable for the endpoint. Final accrual is reported as 4 patients, but that is not an analyzed denominator and cannot be used to infer response evaluability.
The analysis population is not reported in the registry record. No intention-to-treat, per-protocol, or evaluable-participant definition is given. The endpoint assessment schedule is described as every 3 months if a patient is less than 2 years from study entry and every 6 months if a patient is 2 - 3 years from study entry, up to 3 years. That schedule alone does not specify which assessments would contribute to an analysis or how assessments at different times would be combined.
Interim analysis plans and sample-size justification are not reported in the registry record. These details should not be inferred from the phase or the sample-size planning assumptions. The record's statement that no formal analysis is planned is the principal constraint: the outcome result, analysis population, and methods for missing data and multiplicity cannot be assessed.
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 |
|---|---|---|---|
| Depsipeptide | 1 | 4 | 25.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Depsipeptide | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Depsipeptide |
|---|---|---|
| Hypocalcemia | Metabolism and nutrition disorders | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Depsipeptide |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 3 of 4 |
| Fatigue | General disorders | 3 of 4 |
| Nausea | Gastrointestinal disorders | 3 of 4 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 3 of 4 |
| Creatinine increased | Investigations | 3 of 4 |
| Platelets decreased | Investigations | 2 of 4 |
| Vomiting | Gastrointestinal disorders | 2 of 4 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 4 |
| Hyperglycemia | Metabolism and nutrition disorders | 2 of 4 |
| Anorexia | Metabolism and nutrition disorders | 1 of 4 |
Serious events with the highest arm-level rate: hypocalcemia (25.0%).
The adverse-event summary lists a Depsipeptide group, with 4 at risk in the serious-event fields and 1 affected. For the other-event fields, it lists 4 at risk and 4 affected. The registry also lists hypocalcemia among the top serious terms at 25.0%. These are the posted figures; they do not provide a complete account of event severity, timing, duration, recurrence, or attribution.
A percentage attached to a serious-event term describes the recorded frequency in the registry's summary, not the probability of an event in a broader population. With final accrual of 4 patients and early termination for slow accrual, the safety figures should be read as limited descriptive information, not as a stable estimate of risk. The record does not provide enough detail to interpret how the listed term relates to all serious events or to determine whether other serious terms occurred.
Deaths are not reported in the registry record. This should not be read as evidence that no deaths occurred; it means the record does not provide a value for that item. Likewise, the adverse-event figures do not establish a causal relationship to depsipeptide. They are registry summaries, not a comparative safety analysis, because the trial has no control group and reports no formal outcome analysis.
12. What the Result Does, and Does Not, Mean
The record does establish the trial's intended question: whether patients receiving depsipeptide had a complete or partial response under the specified RECIST criteria. It also documents the treatment regimen, single-group design, early termination for slow accrual, and final accrual of 4 patients. These details describe what the study set out to do and the context in which it stopped.
The record does not establish the observed response proportion. It reports no response count, analyzed denominator, estimate, or confidence interval, and states that there are no plans for a formal analysis of any outcome measure. Therefore, the posted information cannot show how frequently the defined response occurred or how precisely that frequency could be estimated. Missing outcome reporting is not equivalent to a finding of no response.
Nor does the record establish a comparative treatment effect. The study is single group, with no randomized comparator. A response result from a single group, even if available, would describe observations among treated participants and would not by itself provide a randomized comparison with another approach. No causal conclusion follows from the design information alone.
The adverse-event summary provides limited descriptive counts and lists hypocalcemia at 25.0% among the top serious terms. It does not provide the detail needed to characterize the overall safety experience or compare it with another group. Deaths are not reported in the registry record. The safety summary should not be expanded into claims about causation or broader risk.
In short, the registry supports conclusions about the planned endpoint and trial conduct, but not a quantitative conclusion about response, precision, or comparative benefit. It also does not provide a complete basis for judging safety. The distinction is important: an endpoint definition, accrual figure, and adverse-event summary are not substitutes for a formal outcome analysis.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between registering an outcome and reporting an analyzed result. The registry defines a response endpoint in operational terms and gives an assessment schedule, but it states that no formal analysis is planned. A clearly specified endpoint can make the research question understandable; without a reported estimate and uncertainty, it does not answer that question quantitatively.
The record also shows why accrual and study status belong in statistical interpretation. The trial was terminated early because of slow accrual, with final accrual of 4 patients. Such context is essential when considering what evidence the record can support. Here, the absence of a formal outcome analysis means that neither response frequency nor precision can be evaluated.
The single-group design further clarifies the difference between describing outcomes and estimating a comparative effect. It has no randomized control arm, so the registered question is not a direct between-treatment comparison. This design feature is not repaired by a response definition or by a planning illustration based on two-arm assumptions.
For biostatisticians and clinical researchers, the record is a useful reminder to distinguish design specifications, planning assumptions, observed data, and inferential results. A protocol-style description can state the intended outcome and the method planned to express uncertainty. Only a reported analysis can show the estimate and its precision. When those results are absent, conclusions should remain limited to the information actually recorded.
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 principal limitation is that the registry record reports no formal outcome analysis. It does not provide a response count, analyzed denominator, response proportion, or confidence interval for the primary endpoint. The endpoint's stated 95% confidence interval is therefore a planned type of summary, not a reported result.
Accrual was limited: the record says the trial terminated early because of slow accrual and had final accrual of 4 patients. This limits the amount of outcome information available in the record. The analysis population and number of participants evaluable for response are not reported, so final accrual should not be mistaken for the endpoint denominator.
The single-group design has no concurrent comparator, and masking is recorded as none. The design cannot provide a randomized estimate of a difference between treatments. Also, the registry does not report participant-level characteristics, response assessments, treatment completion, or the handling of unavailable assessments. These omissions prevent a fuller assessment of the study population, follow-up, and endpoint implementation.
The registry lists a serious adverse-event term and other adverse-event counts, but does not report detailed event descriptions, timing, duration, or attribution. Deaths are not reported in the registry record. Multiplicity procedures, missing-data methods, analysis populations, interim analyses, and sample-size justification are also not reported. These limitations are specific to the available record and should not be replaced with assumptions about the original protocol or conduct.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: FR901228 in Treating Patients With Unresectable Stage III or Stage IV Malignant Melanoma — NCT00104884.
- Registry record last updated 2023-06-28; status last verified 2023-06.
- Results first posted 2016-03-02.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a phase II, single-group study of depsipeptide in unresectable stage III or stage IV malignant melanoma. The recorded regimen was a 4-hour IV infusion of 13 mg/m^2 weekly for 3 weeks, with cycles repeated every 28 days until unacceptable toxicity or disease progression.
The primary endpoint was the proportion of patients with complete or partial response by RECIST, with assessment scheduled at stated intervals up to 3 years. The trial was terminated early because of slow accrual, with final accrual of 4 patients. No formal analysis was planned for any outcome measure, and no response estimate or confidence interval is reported.
The adverse-event summary lists hypocalcemia at 25.0% among the top serious terms. Deaths, analysis population, missing-data methods, and a formal outcome analysis are not reported in the registry record. The available information supports a description of trial design and reporting status, but not a quantitative conclusion about response or comparative treatment effect.