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 Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder (NCT01310803), a randomized phase 3 study. The primary outcome is To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01310803 |
| Phase | Phase 3 |
| Condition | Carcinoma in Situ, Transitional Cell Carcinoma, Non-muscle Invasive Bladder Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Endo USA Inc., a Keenova Therapeutics Company |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with carcinoma in situ (CIS) of the bladder who had received valrubicin induction. The registry also lists transitional cell carcinoma and non-muscle invasive bladder cancer among the conditions. The planned stratification distinguished CIS with papillary disease from CIS only, and considered time since the last BCG failure. The primary outcome record says no analysis was completed because enrollment was limited to 1 subject before termination.
Intervention
The intervention was maintenance therapy with valrubicin following valrubicin induction. The study description specifies 10 monthly intravesical administrations. The registry names the maintenance intervention as VALSTAR and identifies the study as a Phase 3b evaluation of efficacy and safety.
Comparator
The comparison was no maintenance, described as standard of care. Subjects assigned to this arm were not to receive additional intravesical therapy. Both groups had valrubicin induction; the contrast concerned whether maintenance treatment followed induction.
Primary question
The primary question was whether the time from randomization to a defined clinical event differed between maintenance therapy and no maintenance during the stated 2 years. An event included tumor recurrence, progression to muscle-invasive bladder cancer, metastatic bladder cancer, or death from any cause, whichever occurred first. Recurrence or progression required documentation by biopsy or transurethral resection. The registry record contains no completed efficacy comparison, so it does not answer whether the groups differed.
3. Trial Design
This was a Phase 3b, randomized, open-label, parallel-arm, multicenter study sponsored by Endo USA Inc., a Keenova Therapeutics Company. Its stated purpose was to evaluate maintenance valrubicin after valrubicin induction against induction alone in subjects with CIS of the bladder. Randomization was planned in a 1:1 allocation, with stratification by tumor type and time from the last BCG failure. The registry does not report the method used to generate the random sequence or how assignment was concealed.
The maintenance arm was assigned monthly intravesical valrubicin administrations; the comparator arm was no additional intravesical therapy. Because masking was listed as none, the trial was open-label. The record does not describe blinding of outcome assessors or other procedures to reduce the influence of knowledge of treatment assignment.
The registry lists a start date of 2011-05 and primary completion of 2012-01, and marks the study as terminated. Enrollment was 1. The primary outcome description explicitly states that no analysis was completed because of limited enrollment before termination. The reason for termination, the number screened or eligible, and the timing and treatment assignment of the enrolled subject are not reported in the registry record. The planned allocation and stratification describe the design, not evidence that the intended balance between groups was achieved.
The listed secondary outcome concerned the safety and tolerability of maintenance valrubicin after induction compared with induction alone. The record does not provide a completed comparative safety analysis. These design features establish what the trial set out to compare, but the very limited enrollment and absence of a primary efficacy analysis leave the clinical comparison unresolved.
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 | Maintenance Therapy | No Maintenance (Standard of Care) |
|---|---|---|
| STARTED | 1 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Maintenance Therapy | No Maintenance (Standard of Care) |
|---|---|---|
| Subject terminated by Sponsor | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: No analysis completed due to limited enrollment (1 subject) prior to study termination.
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 | Maintenance Therapy | No Maintenance (Standard of Care) | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 0 | 1 | |
| Age, Categorical: <=18 years | Participants | 0 | — | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | — | 0 |
| Age, Categorical: >=65 years | Participants | 1 | — | 1 |
| Sex: Female, Male: Female | Participants | 0 | — | 0 |
| Sex: Female, Male: Male | Participants | 1 | — | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | — | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | — | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | — | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | — | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | — | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | — | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | — | 0 |
| Race (NIH/OMB): White | Participants | 1 | — | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | — | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder., measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the interval from randomization to the first qualifying event, with a stated timeframe of 2 years. The event definition combined tumor recurrence at any stage or grade, progression to muscle-invasive bladder cancer, metastatic bladder cancer, and death from any cause. Whichever event occurred first counted, and tumor recurrence or progression had to be documented by biopsy or transurethral resection of bladder tumor.
A time-to-event endpoint can represent both whether an event occurs and how long participants remain event-free during follow-up. Combining events into a single endpoint can capture several clinically important ways that a participant's status may worsen. It also means the endpoint is not a measure of tumor recurrence alone: the components differ, and a composite result can be influenced by which component occurs. The registry does not report component-specific results.
In general, time-to-event analyses account for the fact that participants may have different follow-up durations, including cases where no event has been observed by the end of observation. The registry record does not report an analysis, event count, censoring details, or follow-up completeness for this endpoint. It therefore does not establish an estimated event rate, a comparison between arms, or the precision of any treatment-effect estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison but does not report a completed primary efficacy analysis. It gives enrollment as 1 and states that no analysis was completed because of limited enrollment before termination. Consequently, there is no reported treatment-effect estimate, confidence interval, or efficacy test to interpret. The record cannot establish whether maintenance valrubicin differed from no maintenance on the specified time-to-event endpoint.
The endpoint was intended to capture time from randomization to the earliest of recurrence, progression to muscle-invasive disease, metastatic disease, or death from any cause. That design question remains distinct from the findings: defining a measurable outcome does not create an estimate when the outcome analysis was not completed. Likewise, randomization and an intended 1:1 allocation describe the planned comparison, not evidence of a reliable group contrast in this record.
The registry labels the study terminated, but does not report why it was terminated. It also does not report a completed primary analysis, component-specific event results, a treatment-effect estimate, or measures of uncertainty. No inference about the direction or size of an efficacy difference is supported by the posted results. The absence of an efficacy analysis should not be recast as evidence that the treatments were equivalent or that either strategy had no effect.
The sample-size material describes planning illustrations based on stated assumptions, including two-sided significance level 0.05, equal allocation, and a normal approximation. Such illustrations are not observed power and do not substitute for a trial result. In this record, the primary outcome reports no completed analysis, and the displayed planning assumptions do not provide an efficacy estimate that can be interpreted as a finding.
The safety entries are similarly limited. The registry lists zero serious adverse events among 1 at risk in the maintenance group and zero among 0 at risk in the no-maintenance group. These entries do not support a meaningful comparative safety conclusion. The no-maintenance group has no participants listed at risk in these safety fields, and the registry provides no completed comparative safety analysis. The death fields are not reported in the registry record.
Overall, the record is informative about the planned question and the trial's termination status, but not about comparative efficacy or safety. A reader should distinguish the study's objective, its recorded enrollment and status, and the absence of analyzed outcome results. The main statistical conclusion is that the intended comparison remains unanswered in the registry record.
9. Statistical Methods Explained
Randomization is intended to assign treatment by chance rather than by clinical judgment or participant characteristics. In general, this can reduce systematic differences between treatment groups, although it cannot guarantee balance in every trial. The registry describes random assignment and a planned 1:1 allocation. It does not report the sequence-generation method, allocation concealment, or implementation details. With enrollment of 1, the record does not provide a basis for assessing whether randomization achieved comparable groups.
Stratification means that randomization is organized within prespecified categories, here tumor type and time from the last BCG failure. In general, this approach aims to help distribute those characteristics across treatment groups. The registry describes the categories but does not report the actual allocation within them or whether the stratification was implemented as planned. It also does not report an analysis adjusted for these factors.
The parallel-arm design assigns participants to one of the treatment strategies and follows the assigned groups. The open-label designation means masking was not used, according to the registry. In general, lack of masking can affect treatment delivery, reporting, or outcome assessment, especially when judgments are involved. Requiring biopsy or transurethral resection documentation for recurrence or progression specifies how those components were to be confirmed, but the registry does not report assessor blinding or the actual outcome-assessment procedures.
The primary outcome is a time-to-event measure. In general, a time-to-event analysis uses the time until an event and accounts for participants whose event status is not observed through the full follow-up period. Such participants may be censored, meaning their observed follow-up contributes information up to the point they are last known to be event-free, without treating that point as an event. This explanation is general; the registry record does not report its censoring rules, follow-up procedures, or a completed time-to-event analysis.
A confidence interval, in general, describes a range of estimates compatible with the data under the model and method used. Its width communicates precision: broader intervals indicate less precision than narrower intervals. No primary efficacy estimate or confidence interval is reported in this record, so there is no interval from which to assess precision or statistical compatibility with particular effects.
A significance test, in general, evaluates how compatible the observed data are with a specified null hypothesis under assumptions of the test. A p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. The registry record does not report a primary efficacy test or p-value. Therefore, there is no reported test result to classify as statistically significant or not statistically significant.
The sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. For time-to-event calculations, the assumptions refer to total events; other calculations refer to participants per arm. In general, a planning illustration estimates the information or enrollment that might be needed under its assumptions. It is not a study finding and is not observed power. The registry does not report the trial's own sample-size justification, and the stated primary outcome has no completed analysis. The actual numerical planning results should therefore not be interpreted as efficacy results.
Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If a model underestimates variability, standard errors and confidence intervals can be misleading, and tests may be poorly calibrated. The registry record does not report a count-based outcome analysis or a model in which over-dispersion could be assessed. No claim about an over-dispersion adjustment can be made for this trial.
Multiplicity arises in general when multiple outcomes, comparisons, subgroups, or time points are tested. Without an analysis plan, it is not possible to determine whether or how the chance of false-positive findings was controlled across analyses. The registry lists a primary efficacy objective and a secondary safety and tolerability objective, but does not report a statistical analysis plan or completed analyses. The record does not specify a multiplicity procedure.
These concepts describe how trial analyses are commonly interpreted; they do not establish what methods were used in this study. Apart from the stated design and planning assumptions, the statistical analysis plan is not reported in the registry record. No adjustment strategy, missing-data method, analysis population definition, or interim analysis is reported.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary efficacy objective and a secondary safety and tolerability objective. It does not report a statistical analysis plan that specifies how multiple outcomes, comparisons, or any subgroup analyses would be handled. In general, testing multiple hypotheses can increase the chance of a false-positive result unless the approach is prespecified and interpreted accordingly. No multiplicity adjustment or testing hierarchy is reported in the registry record. Since no primary efficacy analysis was completed, the record contains no collection of efficacy tests to evaluate for multiplicity.
The primary outcome states that no analysis was completed because enrollment was limited to 1 subject before termination. The registry does not describe an analysis population, such as an intention-to-treat or per-protocol population, or explain how participants would be included in a completed analysis. It also does not report a missing-data strategy, follow-up completeness, or rules for censoring in the time-to-event analysis. These omissions mean the handling of missing outcome information cannot be assessed.
Missing data and absent analysis results are not interchangeable. The record states that the primary analysis was not completed; it does not provide enough information to characterize the completeness of individual outcome data or to determine why analyses were unavailable. The reason for termination is also not reported in the registry record. No interim analysis or stopping rule is reported, and none should be inferred from the terminated status.
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 |
|---|---|---|---|
| Maintenance Therapy | 0 | 1 | 0.0% |
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 |
|---|---|
| Maintenance Therapy | 0 of 1 |
| No Maintenance (Standard of Care) | 0 of 0 |
The safety record lists serious adverse events for the maintenance and no-maintenance groups. For maintenance therapy, it reports 1 at risk and 0 affected. For no maintenance, it reports 0 at risk and 0 affected. These are descriptive registry entries, not a completed comparative safety analysis. In particular, zero participants listed at risk in the no-maintenance safety fields means that the zero affected entry cannot be read as evidence of no serious adverse events in an observed group.
The registry also reports zero other adverse events among 1 at risk for maintenance therapy and zero among 0 at risk for no maintenance. These small entries cannot establish comparative safety or rule out uncommon harms. The death fields are not reported in the registry record, and no serious adverse event terms are listed. The record does not describe follow-up duration for the safety entries or provide an analysis comparing groups.
In general, adverse-event counts need to be interpreted alongside the number of people observed, follow-up time, event definitions, and collection methods. Here, enrollment was 1 and the study was terminated without a completed primary analysis. The available safety entries are too limited to support a broad conclusion about tolerability or risk.
12. What the Result Does, and Does Not, Mean
The trial was designed to compare maintenance valrubicin after valrubicin induction with no maintenance after induction in subjects with bladder CIS. Its primary endpoint was time from randomization to a composite event over the stated 2 years. The registry record reports that the study was terminated and that enrollment was 1. It explicitly says no primary efficacy analysis was completed because of limited enrollment.
Accordingly, the record does not show whether maintenance was associated with a longer or shorter time to the defined event, or whether there was any difference between groups. It contains no completed effect estimate or precision measure for that comparison. The absence of a reported result is not evidence that the groups were the same, and it does not establish that either strategy did or did not affect the endpoint.
The safety entries also do not establish comparative safety. The number listed at risk differs between the arm records, and no participants are listed at risk in the no-maintenance safety fields. The registry does not report a completed comparative safety analysis or death results. The sparse entries should not be generalized beyond what is recorded.
The planning assumptions are not trial findings. Sample-size illustrations can help describe what a future or adequately analyzed study might require under specified assumptions, but they do not recover missing outcome information or demonstrate observed power. The registry does not report the trial's own sample-size justification, analysis plan, or reason for termination.
The appropriate interpretation is therefore narrow: the record documents a planned randomized comparison and its termination after limited enrollment, but leaves the efficacy and comparative safety questions unresolved. It does not support a claim of benefit, lack of benefit, equivalence, or absence of harm.
13. Why This Trial Matters Statistically
This trial is statistically important as an example of the distinction between a well-defined research question and an answer supported by analyzed data. The registry sets out a randomized comparison, describes the treatment strategies, and defines a time-to-event endpoint. Yet the record also reports enrollment of 1 and no completed primary efficacy analysis. A clear endpoint and planned allocation do not compensate for the absence of an analyzable comparison.
The record also illustrates why a termination label needs context. The study is marked terminated, but the reason is not reported in the registry record. The outcome description links the lack of analysis to limited enrollment; it does not establish the broader circumstances that led to termination. Separating reported details from possible explanations is essential when interpreting incomplete trials.
Another statistical lesson concerns planning calculations. Sample-size illustrations depend on assumptions about the effect and analysis method. They can inform planning, but they are not observed evidence and should not be described as power achieved by this trial. A planning result cannot replace an estimate, confidence interval, or analysis of outcomes actually observed.
Finally, the safety entries show why denominators matter. A zero event count alongside zero participants listed at risk cannot be read as reassurance about an unobserved group. Descriptive counts require context about who was observed and for how long. In this record, the safety information is too limited for a comparative 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 central limitation is the absence of a completed primary efficacy analysis. The registry attributes this to limited enrollment of 1 subject before termination. Without an analyzed comparison, there is no treatment-effect estimate or measure of uncertainty for the specified time-to-event endpoint. The registry does not report the reason for termination.
The intended 1:1 randomization and stratification are design descriptions. The record does not report the sequence-generation process, allocation concealment, actual implementation of stratification, or enough analyzed participants to assess group comparability. The study was open-label, and the registry does not report whether outcome assessors were masked.
The endpoint combines recurrence, progression, metastatic disease, and death. Component-specific results are not reported, and no event or censoring details are available for interpreting time-to-event outcomes. The registry also does not report follow-up completeness or how missing outcome information would have been handled.
The safety record is limited: it lists 1 at risk in the maintenance group and 0 at risk in the no-maintenance group, with zero affected in both entries. These fields do not provide a meaningful between-group comparison. Death results are not reported in the registry record. The sample-size material is described as planning illustration rather than the trial's own design justification, and no completed analysis is available to connect those calculations to a trial result.
Further limitations include the absence of a reported statistical analysis plan, defined analysis populations, multiplicity approach, or interim analysis information. These details are not reported in the registry record and should not be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Multi-center Study to Evaluate the Efficacy and Safety of Maintenance Therapy With Valrubicin Versus no Maintenance, in Subjects Treated With Valrubicin Induction for Carcinoma in Situ (CIS) of the Bladder — NCT01310803.
- Registry record last updated 2017-10-05; status last verified 2017-09.
- Results first posted 2014-10-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01310803 was a Phase 3b randomized, open-label, parallel-arm, multicenter study of valrubicin maintenance after valrubicin induction compared with no maintenance in subjects with CIS of the bladder. Randomization was planned in a 1:1 allocation, with stratification by tumor type and time from the last BCG failure.
The primary endpoint was time from randomization to recurrence, progression to muscle-invasive bladder cancer, metastatic bladder cancer, or death from any cause, with a stated timeframe of 2 years. The registry lists enrollment of 1, a status of terminated, and no completed primary efficacy analysis due to limited enrollment before termination. The reason for termination is not reported in the registry record. The available safety entries do not support a comparative conclusion.