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 Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma (NCT00808639), a na phase 2 study. The primary outcome is Number of Patients Achieving Pathologic Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00808639 |
| Phase | Phase 2 |
| Condition | Bladder Cancer, Muscle-invasive Bladder Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 39 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Dana-Farber Cancer Institute |
| Results posted | Yes |
2. Clinical Question
Population
The registry describes subjects with muscle-invasive urothelial carcinoma, including muscle-invasive bladder cancer. The analysis population for the primary outcome is stated to consist of all enrolled patients. Enrollment was 39.
Intervention
The study evaluated neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, identified as ddMVAC, with pegfilgrastim support. The registry describes chemotherapy followed by radical surgery. The primary endpoint was assessed after completion of 4 chemotherapy cycles with pegfilgrastim support; the cycle length was 2 weeks.
Comparator
There was no concurrent comparison group: the design is listed as single group, with allocation recorded as NA. The study was unmasked. Consequently, the registry record does not establish a randomized or like-for-like comparison against another treatment or control group.
Primary question
The primary question was how many enrolled patients achieved a pathologic response after the chemotherapy regimen. Response was defined as down-staging to at or below pT1, N0 after chemotherapy with pegfilgrastim support. The registry identifies the outcome as a number of patients and gives a percentage of pathologic responders as its unit. The observed response count, percentage, and 90% confidence interval are not reported in the registry record.
This is a question about the frequency of a defined pathologic finding in the studied group, not a randomized estimate of the regimen's effect relative to an alternative. The registry also lists febrile neutropenia and surgery-related toxicity as secondary outcomes. Their outcome values are not reported in the registry record. Without those results, the available record describes the intended clinical question and endpoint definition, but it does not provide enough information to quantify the primary response or secondary outcomes.
3. Trial Design
The registry identifies NCT00808639 as a completed Phase II trial sponsored by Dana-Farber Cancer Institute. Its title concerns dose-dense MVAC with pegfilgrastim support in subjects with muscle-invasive urothelial carcinoma. The listed enrollment is 39. The registry records the study start as 2008-12 and primary completion as 2013-12.
The design is single group, and allocation is recorded as NA. Masking is listed as none. These details mean the record describes one treatment group without a concurrent randomized comparator. The arm is called Dose Dense MVAC and is described as chemotherapy with methotrexate, vinblastine, Adriamycin, and cisplatin. The brief summary identifies the regimen as neoadjuvant ddMVAC in combination with pegfilgrastim, followed by radical surgery. The listed drug interventions are methotrexate, doxorubicin, vinblastine, cisplatin, and pegfilgrastim.
The primary endpoint is assessed after completion of 4 cycles of chemotherapy with pegfilgrastim support, with a cycle length of 2 weeks. The record defines a pathologic response by down-staging to at or below pT1, N0 after chemotherapy. It states that the analysis population consists of all enrolled patients. The registry also names febrile neutropenia and surgery-related toxicity as secondary outcomes.
A single-group design can describe outcomes observed among people receiving the regimen, but it does not by itself separate a treatment effect from other explanations for the observed outcome. Without a randomized comparison, differences from an external or historical group would require additional information and assumptions; such a comparison is not described in the registry record. The record does not report the protocol details, treatment completion, surgery timing, or follow-up beyond the primary endpoint timeframe. It also does not report the outcome results.
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 | Dose Dense MVAC |
|---|---|
| STARTED | 39 |
| COMPLETED | 38 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Dose Dense MVAC |
|---|---|
| Disease progression before surgery. | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis population consists of all enrolled patients.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Dose Dense MVAC |
|---|---|---|
| Participants analysed | 39 | |
| Age, Continuous | years | 57 (43 to 76) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 28 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 39 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 39 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Achieving Pathologic Response, measured over After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 90% Confidence Interval |
| Unit | percentage of pathologic responders |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of patients achieving pathologic response, expressed as a percentage of pathologic responders. The registry defines response as down-staging to at or below pT1, N0 after chemotherapy with pegfilgrastim support. Assessment is specified after completion of 4 cycles, each with a length of 2 weeks. The stated analysis population consists of all enrolled patients.
Pathologic response is based on the disease stage recorded from tissue assessment after treatment, rather than on a symptom score or a time-to-event measure. In general, a prespecified pathologic threshold makes the outcome interpretable as whether a patient meets a defined classification after treatment. The endpoint can therefore describe the proportion of the stated analysis population meeting that threshold, if the count and denominator are available.
The registry record does not report the observed number meeting the response definition, the corresponding percentage, or the 90% confidence interval. It also does not provide details about how patients without an assessment were handled. Those omissions prevent a reader from determining the observed response frequency or its precision from the registry record alone. The endpoint definition identifies what was intended to be counted; it is not itself evidence of the result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives a clearly stated primary outcome definition and timeframe, but it does not report the primary outcome result. There is no reported response count, percentage, or 90% confidence interval. Therefore, the recorded information cannot establish how frequently the defined pathologic response occurred among the stated analysis population, nor how precisely that frequency was estimated.
The design context is important when interpreting any outcome that might be reported elsewhere. This was a single-group study with no allocation to a comparator and no masking. A proportion observed in a single group describes the outcome in that group under the study conditions. By itself, it does not estimate the difference between the regimen and another treatment, nor can it show what would have happened to the same patients under a different approach. The registry's completed status does not substitute for reporting the measured results.
The primary endpoint concerns pathologic down-staging after treatment, not a direct measure of long-term disease control or survival. The registry specifies the assessment after 4 cycles of chemotherapy with pegfilgrastim support. It does not report later clinical outcomes or the duration of follow-up for such outcomes. It would therefore be inappropriate to infer longer-term benefit or harm from this endpoint definition alone.
The registry identifies febrile neutropenia and surgery-related toxicity as secondary outcomes, but their outcome values are not reported. Serious and other adverse-event counts are listed separately for the Dose Dense MVAC group. Those counts provide safety reporting within the group; without a comparator, they do not quantify excess risk attributable to the regimen. The record's listed serious-event terms and percentages should be read as reported categories, not as a complete description of every possible event or a comparison with another group.
The primary endpoint includes a stated 90% confidence interval as its dispersion measure, but the interval limits are not reported in the registry record. In general, a confidence interval communicates uncertainty around an estimated quantity; its width depends on the estimate and the information available. Without the limits, the precision of the primary response estimate cannot be assessed. The sample-size assumptions describe a planning illustration based on an observed effect, but the record does not report the observed primary effect or numerical planning results. That illustration should not be treated as evidence about the trial's actual design or as observed power.
Overall, the registry supports description of the study question, design, endpoint definition, and selected safety counts. It does not support a numerical conclusion about the primary response, a comparative treatment effect, or the precision of the response estimate. Those distinctions are essential: a completed study and a specified endpoint do not reveal an unreported result.
9. Statistical Methods Explained
The registry characterizes the primary outcome as a number of patients achieving pathologic response, with a percentage of pathologic responders as the unit and a 90% confidence interval as the dispersion measure. The endpoint is assessed after 4 cycles of chemotherapy with pegfilgrastim support, with a cycle length of 2 weeks. The stated analysis population is all enrolled patients. These details specify the intended outcome, assessment time, and population, but the response estimate and interval limits are not reported in the registry record.
What does a confidence interval describe?
In general, a confidence interval expresses the uncertainty around an estimated quantity under the statistical method used to construct it. For a response percentage, the interval gives a range of values compatible with the observed information under that method. It is not a range containing a fixed share of individual patient outcomes, and it does not account automatically for every source of bias or uncertainty in the design. The registry names a 90% confidence interval but does not report its bounds or the method used to calculate it. Its actual width and the resulting precision therefore cannot be assessed from the registry record.
What does a single-group result estimate?
In general, a single-group outcome rate describes the observed frequency of an outcome in the group studied. The design listed for this trial is single group, with allocation recorded as NA and masking listed as none. There is no concurrent control group in the registry description. Thus, even if a response percentage were reported, it would be a description of the studied group rather than a randomized estimate of the difference between treatments. A causal comparison would require a suitable comparator and a design or analysis that supports that comparison. Neither is described in this record.
How should the endpoint definition be read?
The registry defines response as down-staging to at or below pT1, N0 after chemotherapy with pegfilgrastim support. This is a threshold-based outcome: each assessed patient either meets the stated classification or does not, according to the recorded definition. In general, using a prespecified threshold helps make the outcome more consistent to interpret. However, the registry record does not report the pathology assessment procedures, any adjudication process, or how a missing assessment would be classified. It also does not report the actual number of patients meeting the threshold.
What does the planning illustration mean?
The registry's sample-size assumptions describe a planning illustration computed from an observed effect, not the trial's own design. The listed assumptions are 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 outcomes, the assumptions refer to a total number of events; for other outcomes, they refer to participants per arm. These are planning concepts, not observed trial outcomes.
This trial is recorded as a single-group study, whereas the planning illustration assumes equal allocation between two arms. The illustration should therefore not be mistaken for a description of the actual allocation or enrollment plan. A planning calculation asks what sample size would be needed under specified assumptions; it does not show that the study had that size, that the assumptions were met, or that a result has a particular probability of being significant. It is not observed power. The numerical planning outputs and the observed effect used for the illustration are not reported in the registry record.
Why does over-dispersion matter in general?
For count outcomes, a simple statistical model may assume that variability follows a specified distribution. Over-dispersion means the observed variability is greater than that model assumes. In general, failing to account for excess variability can make uncertainty estimates too small and statistical evidence appear more precise than warranted. This trial's primary outcome is described as a number of patients achieving a response, with a percentage as the unit. The registry does not report an over-dispersion assessment or a model for the primary endpoint, so no claim about its relevance to this analysis can be made.
The registry lists one analysis and three outcome measures. It does not report a detailed statistical analysis plan, a method for constructing the primary confidence interval, or procedures for handling missing outcome assessments. Those omissions limit independent assessment of how the endpoint was analyzed. General statistical principles can explain the role of intervals and design, but they cannot supply the missing numerical result or analysis details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures: the primary pathologic-response outcome and secondary outcomes concerning febrile neutropenia and surgery-related toxicity. It also lists one analysis. The record does not report a multiplicity strategy, such as whether any adjustment was planned for evaluating more than one outcome or how secondary outcomes were intended to be interpreted. Without such information, the record does not establish whether reported tests, if any, were treated as confirmatory or exploratory.
The primary analysis population is described as all enrolled patients. This identifies the intended population for the pathologic-response outcome, but the registry record does not report how many patients had an evaluable pathology assessment or how missing assessments were handled. It does not say whether patients who did not complete chemotherapy, did not proceed to surgery, or lacked a response assessment were included in a particular way. These details matter because the percentage depends on the analysis population and the outcome classification rules. No particular handling rule should be assumed.
The record does not report imputation methods, sensitivity analyses, exclusions from the primary analysis, or a detailed plan for missing data. It also does not report whether the listed secondary outcomes were analyzed for all enrolled patients or another population. These absences do not prove that such procedures were not used; they mean the procedures are not reported in the registry record. The stated all-enrolled population is the only explicit population definition for the primary outcome.
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 |
|---|---|---|---|
| Dose Dense MVAC | 4 | 39 | 10.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Dense MVAC | 32 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Dense MVAC |
|---|---|---|
| Muco/stomatitis by exam, oral cavity | Gastrointestinal disorders | 1 of 39 |
| Infection w/ gr3-4 neut, urinary tract | Infections and infestations | 1 of 39 |
| Hypokalemia | Metabolism and nutrition disorders | 1 of 39 |
| Hand-foot reaction | Skin and subcutaneous tissue disorders | 1 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Dense MVAC |
|---|---|---|
| Fatigue | General disorders | 27 of 39 |
| Nausea | Gastrointestinal disorders | 15 of 39 |
| Constipation | Gastrointestinal disorders | 9 of 39 |
| Muco/stomatitis (symptom) oral cavity | Gastrointestinal disorders | 9 of 39 |
| Anorexia | Metabolism and nutrition disorders | 8 of 39 |
| Taste disturbance | Nervous system disorders | 7 of 39 |
| Head/headache | Nervous system disorders | 5 of 39 |
| Muco/stomatitis by exam, oral cavity | Gastrointestinal disorders | 4 of 39 |
| Vomiting | Gastrointestinal disorders | 4 of 39 |
| Tinnitus | Ear and labyrinth disorders | 3 of 39 |
Serious events with the highest arm-level rate: muco/stomatitis by exam, oral cavity (2.6%), infection w/ gr3-4 neut, urinary tract (2.6%), hypokalemia (2.6%), hand-foot reaction (2.6%).
The registry lists serious and other adverse-event counts for the Dose Dense MVAC group. For serious adverse events, 39 were listed as at risk and 4 as affected. For other adverse events, 39 were listed as at risk and 32 as affected. These are separate registry categories and should not be combined or treated as a comparative estimate. The death count is not reported in the registry record.
The listed serious-event terms are Muco/stomatitis by exam, oral cavity; Infection w/ gr3-4 neut, urinary tract; Hypokalemia; and Hand-foot reaction. Each is accompanied by 2.6%. The registry does not provide event-level narratives or enough detail to determine severity beyond the listed classifications, timing, duration, recurrence, or relationship to treatment. These categories and percentages describe the registry's reported safety entries; they do not establish that every event in the group is represented by the listed terms.
In general, adverse-event counts describe events or affected participants according to the reporting framework. Without a concurrent control group, they cannot quantify how the frequency compares with another treatment or what would have occurred without the regimen. The registry record does not provide a comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The record describes a completed Phase II, single-group study of neoadjuvant dose-dense MVAC with pegfilgrastim support in subjects with muscle-invasive urothelial carcinoma. It specifies a primary pathologic-response definition, an assessment after 4 cycles, and an analysis population consisting of all enrolled patients. It also lists safety counts and named secondary outcomes. These details clarify what the trial set out to study and how the primary outcome was framed.
However, the primary response count, percentage, and 90% confidence interval are not reported in the registry record. Without those results, the frequency of response and its precision cannot be evaluated. The listed secondary outcomes also lack reported results in the registry record. A study's completion status and its planned endpoint do not disclose the measured findings.
Even if the response estimate were available, the single-group design would support description of outcomes in the treated group, not a randomized comparison with another treatment. The registry lists no concurrent comparator, and masking is listed as none. The design therefore does not, on its own, isolate the effect of the regimen from other explanations for outcomes. The pathologic-response endpoint is also not the same as a reported long-term clinical outcome; the registry record does not provide such outcome results.
The serious and other adverse-event counts describe events recorded in the treatment group. They should not be read as excess risk relative to a control group, because no such group is described. The registry's adverse-event entries do not establish the complete safety profile or the causal relationship of each event to treatment.
The appropriate conclusion is limited: the registry documents the study design, regimen, endpoint definition, and selected safety entries, while leaving the primary efficacy result and several analysis details unreported. No numerical efficacy conclusion or comparative benefit-harm conclusion can be drawn from the registry record alone.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how study design determines what an outcome can answer. A single-group design can estimate an outcome frequency within the studied group, provided the outcome data and analysis are reported. It cannot provide the same direct treatment comparison as a randomized study with a concurrent comparator. The registry identifies this study as single group, with allocation listed as NA and no masking.
The pathologic-response endpoint is defined using a specific staging threshold and assessment timeframe. Such definition is central to interpretation: readers need to know what counts as a response, when it is assessed, and which patients belong in the analysis. The registry states that response means down-staging to at or below pT1, N0 after chemotherapy with pegfilgrastim support, and that the analysis population consists of all enrolled patients. Yet the response count, percentage, and confidence interval are not reported in the registry record. This makes the gap between a well-specified question and an interpretable numerical answer especially clear.
The listed safety counts also illustrate why event frequencies need design context. Counts within one group describe recorded events, but without a comparison group they cannot show how those frequencies differ from another option. The same principle applies to efficacy: an outcome frequency is not itself a comparative treatment effect.
Finally, the planning assumptions should be kept separate from the trial design. The record describes an equal-allocation, two-arm planning illustration, while the study itself is listed as single group. Planning calculations are conditional on assumptions and are not observed power or trial results. Together, these features underscore the importance of reporting outcome estimates, uncertainty, analysis populations, and analysis methods alongside a trial's design.
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 for interpreting the registry record is that the primary outcome result is not reported. Although the response definition, assessment timeframe, analysis population, and confidence-interval level are stated, the response count, percentage, and interval limits are absent. The endpoint's precision and observed frequency therefore cannot be evaluated from the registry record.
The single-group design has no concurrent comparator in the registry description. Outcomes in the treated group cannot, by themselves, establish a comparative effect. The record also lists no masking. These design features should be considered when interpreting any reported outcome, including the serious and other adverse-event counts.
Important analysis details are not reported in the registry record. These include the method used to calculate the confidence interval, the handling of missing pathology assessments, whether all enrolled patients had an evaluable primary outcome, and any sensitivity analyses. The record states that the primary analysis population consists of all enrolled patients, but does not explain how patients without an assessment would be handled.
The registry names febrile neutropenia and surgery-related toxicity as secondary outcomes, but does not report their results or a multiplicity strategy. It also does not report longer-term clinical outcomes or follow-up details beyond the primary endpoint timeframe. The planning illustration's observed effect and numerical planning results are not reported in the registry record, and its two-arm assumptions do not describe the listed single-group design. These limitations restrict what can be concluded from the record; they do not establish what analyses or procedures may have been conducted outside the reported information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma — NCT00808639.
- Registry record last updated 2016-10-24; status last verified 2016-09.
- Results first posted 2014-05-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00808639 is a completed Phase II, single-group study sponsored by Dana-Farber Cancer Institute. The registry lists enrollment of 39 and describes neoadjuvant dose-dense MVAC with pegfilgrastim support for subjects with muscle-invasive urothelial carcinoma, followed by radical surgery. Allocation is listed as NA, and masking as none.
The primary outcome is the number of patients achieving pathologic response, defined as down-staging to at or below pT1, N0 after chemotherapy with pegfilgrastim support. Assessment is specified after 4 cycles, with a cycle length of 2 weeks; the analysis population is all enrolled patients. The registry names febrile neutropenia and surgery-related toxicity as secondary outcomes. It reports serious and other adverse-event counts, but the primary response result and its 90% confidence interval are not reported in the registry record.