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 Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611) (NCT00461591), a randomized phase 3 study. The primary outcome is Recurrence Rate at 2 Years.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00461591 |
| Phase | Phase 3 |
| Condition | Bladder Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 802 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Spectrum Pharmaceuticals, Inc |
| Results posted | Yes |
2. Clinical Question
Population
The primary endpoint population was the Target Ta, G1-G2 population: patients with no more than 4 tumors, each no larger than 3.5 cm at randomization, whose resected tumors were subsequently confirmed by the central pathology lab as Ta, Grade 1 or 2. The condition listed in the registry record is bladder cancer.
Intervention
Participants received TURBT followed by a single intravesical dose of apaziquone. The arm description specifies 4mg in 40ml instilled into the bladder post-TURBT.
Comparator
The comparison group received TURBT followed by a single intravesical dose of placebo instilled into the bladder post-TURBT. The trial was randomized and placebo-controlled.
Primary question
The stated primary question was whether the 2-year recurrence rate differed between the apaziquone and placebo groups. Recurrence was defined as histologically confirmed bladder tumor recurrence after randomization and on or before year 2. The registry record does not report a single arm-to-arm estimate or test for this endpoint, so the direction and precision of the primary comparison cannot be assessed from the posted primary outcome information.
3. Trial Design
This was a phase 3, randomized, placebo-controlled, double-blind, parallel-group trial. The official title describes it as multicenter, and the registry lists quadruple masking. Those labels indicate that masking was part of the design; the registry record does not specify which roles were included in the masking designation or describe how masking was maintained.
The registry lists enrollment of 802. This is the recorded enrollment figure; it should not be treated as an arm-specific analysis population or as the number contributing data to every endpoint. The adverse-event record separately lists participants at risk in each group. The registry record does not provide an account of participant flow, withdrawals, exclusions, or the number included in the primary endpoint analysis.
Both groups underwent transurethral resection of bladder tumor, or TURBT. The experimental group received a single intravesical apaziquone dose after the procedure, while the control group received a single intravesical placebo dose. The primary endpoint description focuses on recurrence by year 2 in a restricted Ta, G1-G2 population, with central pathology confirmation and limits on tumor number and size at randomization. The record does not explain how this target population related to all enrolled participants or how eligibility and pathology confirmation were handled in the analysis.
The study is marked completed. The registry lists a start of 2007-04 and primary completion of 2012-01. These registry dates describe the study record and do not establish when every participant completed follow-up. Secondary outcomes included time to recurrence, progression measures, recurrence counts, disease-free outcomes, and overall survival. The primary endpoint result itself is not reported as a single comparison in the registry record.
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 | Apaziquone | Placebo |
|---|---|---|
| STARTED | 406 | 396 |
| COMPLETED | 317 | 311 |
| NOT COMPLETED | 89 | 85 |
Analysis population for the primary outcome, as defined in the registry: Target Ta, G1-G2 Population: patients who had 4 or fewer tumors that were ≤ 3.5 cm each at the time of randomization and who had subsequent histological confirmation from the central pathology lab that the tumors resected at the time of randomization were Ta, Grade 1 or 2.
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: Safety/ITT Population
| Characteristic | Unit | Apaziquone | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 406 | 396 | 802 | |
| Age, Continuous | years | 67.5 (SD 10.92) | 68.2 (SD 10.72) | 67.8 (SD 10.82) |
| Age, Customized: Age – <65 | Participants | 159 | 146 | 305 |
| Age, Customized: Age – 65-75 | Participants | 140 | 139 | 279 |
| Age, Customized: Age – >75 | Participants | 107 | 111 | 218 |
| Sex: Female, Male: Female | Participants | 108 | 102 | 210 |
| Sex: Female, Male: Male | Participants | 298 | 294 | 592 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 13 | 17 | 30 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 393 | 379 | 772 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 11 | 9 | 20 |
| Race (NIH/OMB): White | Participants | 392 | 383 | 775 |
| Race (NIH/OMB): More than one race | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 381 | 375 | 756 |
| Region of Enrollment: Poland | participants | 25 | 21 | 46 |
6. Primary Endpoint
The registry lists the primary outcome as Recurrence Rate at 2 Years, measured over 2 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was recurrence rate at 2 years, measured as the number of participants with a qualifying recurrence. A recurrence counted if bladder tumor recurrence was histologically confirmed at any time after randomization and on or before year 2. The endpoint is therefore a participant-level binary outcome over a stated follow-up window: each participant either had a qualifying recurrence or did not, provided the outcome was assessed.
A fixed-time recurrence endpoint is used to compare the proportion of participants experiencing the event by a defined time. The time limit matters: an event outside the specified window is not part of this endpoint, even though it could be relevant to a separate time-to-event outcome. The registry also lists time to recurrence as a secondary outcome, which asks a different question by incorporating when an event occurs rather than only whether it occurred within the fixed period.
The endpoint was defined for the Target Ta, G1-G2 population, restricted to participants with no more than 4 tumors, each no larger than 3.5 cm at randomization, and central pathology confirmation of Ta, Grade 1 or 2. These criteria identify the population to which the stated primary question applies. The registry record does not report the arm-specific recurrence counts, percentages, effect estimate, confidence interval, or test result as one primary comparison. Thus the endpoint definition is available, but the magnitude and precision of the between-group result cannot be evaluated from that primary outcome entry.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives a clear primary endpoint definition but does not provide a single apaziquone-versus-placebo estimate for recurrence at 2 years. It therefore does not establish, from the posted primary outcome information, how the groups compared, how large any difference was, or how uncertain the comparison was. No conclusion about the direction or statistical strength of the primary result can be drawn from the endpoint description alone.
This distinction is important because a planned question and an observed result are not interchangeable. The trial was designed to evaluate recurrence after TURBT with apaziquone versus placebo, but the record’s stated objective is not itself evidence of a treatment effect. The registry describes the outcome as a count of participants with histologically confirmed recurrence within the specified period. It does not give a single pair of arm-specific values or an inferential result for that population and time window.
The posted safety information contains group-specific adverse-event counts and selected serious adverse-event terms. Those data address safety reporting, not the primary recurrence comparison. Counts of participants with adverse events cannot substitute for recurrence outcomes, and the listed serious terms do not establish whether an event was caused by treatment. The registry also lists several secondary outcomes, including time to recurrence and progression measures. Their presence indicates additional outcome domains, but their names alone do not supply results.
Confidence intervals, when reported, describe the range of estimates compatible with the data under the analysis assumptions; their width conveys precision. A p-value addresses compatibility with a specified null hypothesis under an analysis model, rather than the clinical importance of an effect. Neither a primary confidence interval nor a primary p-value is reported in the registry entry. The statistical evidence for the primary comparison therefore cannot be characterized as precise, imprecise, statistically significant, or non-significant on the basis of the available primary outcome record.
The enrollment figure and the adverse-event denominators should also be interpreted in context. Enrollment is not necessarily identical to the population analyzed for a particular endpoint. The registry record does not report the primary analysis population or missing-outcome handling. Any reading of the primary endpoint would require those details alongside the arm-specific result. Without them, the defensible interpretation is limited: the registry records the design and endpoint definition, but not a consolidated primary estimate.
9. Statistical Methods Explained
The trial design used random allocation to compare TURBT plus apaziquone with TURBT plus placebo. Randomization is intended, in general, to make treatment groups comparable at the start of a trial with respect to both measured and unmeasured characteristics. This supports an interpretable treatment comparison when allocation is implemented as planned and participants are analyzed appropriately. The registry record does not describe the randomization procedure, allocation concealment, or the analysis method used for the primary endpoint, so those details cannot be assessed.
What a fixed-time binary endpoint represents
The primary outcome was recorded as participants with a recurrence by year 2. This is a binary endpoint at the participant level: recurrence meeting the stated definition within the time window is counted as an event, while no qualifying event is counted as no event, subject to outcome ascertainment. In general, a comparison of binary outcomes can be expressed using group-specific event proportions and an effect measure such as a risk difference, risk ratio, or odds ratio. The choice of effect measure and its statistical model should be reported because they affect interpretation. The registry record does not identify a primary effect measure or provide a single arm-to-arm calculation for this endpoint.
The time boundary is part of the endpoint definition. Recurrence had to be histologically confirmed after randomization and on or before year 2. A fixed-time outcome does not describe the exact timing of events within the window. Time-to-event analysis, listed as a secondary outcome, generally uses event timing and can account for differing follow-up times under its assumptions. The registry record does not provide the time-to-event analysis method or its results.
Precision and statistical uncertainty
A confidence interval is a general statistical tool for expressing uncertainty around an estimated effect. A narrower interval indicates greater precision under the model and assumptions used; an interval spanning effects in different directions can leave the direction uncertain. Statistical significance is not a measure of effect size, and a p-value does not describe the probability that a treatment effect is true. These concepts are relevant when interpreting a primary comparison, but the registry record does not report a primary confidence interval, p-value, or effect estimate. Precision and statistical significance therefore cannot be assessed for the primary endpoint from this record.
Observed event counts and denominators are also essential to interpreting a binary outcome. They show the data from which a proportion is estimated and allow readers to understand how much information contributes to the comparison. The primary outcome entry does not give the required arm-specific recurrence values as one comparison. The adverse-event group counts are not recurrence data and must not be substituted for them.
Planning calculations and trial analysis
The accompanying planning illustrations are described as calculations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. They consider the effect to detect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not proof that the original trial was planned using those assumptions. The registry record does not report the trial’s sample-size justification, the effect assumed for its original design, or whether the planning-illustration assumptions match the protocol.
General sample-size calculations depend on assumptions about the outcome rate, target effect, variability, allocation, significance level, and desired power. If the true effect is smaller than the effect used for planning, a trial may have less ability to distinguish it from random variation. If an effect estimate from completed data is used to generate a planning illustration, that is a different exercise from documenting the original design rationale. The illustrations should therefore be read as hypothetical planning information, not as an outcome of the randomized comparison.
Over-dispersion and model choice
Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. It can make standard errors too small if ignored, which can make confidence intervals too narrow and tests overly optimistic. This concept is more directly relevant to outcomes such as counts than to a simple participant-level binary endpoint. The registry record does not state that over-dispersion was assessed, that a count model was used for the primary outcome, or which model was used for secondary recurrence counts. No claim about model adequacy can therefore be made.
Good interpretation also depends on prespecification and implementation: which outcome was primary, which participants were included, how missing observations were handled, and what statistical test or model was used. The endpoint definition and trial design are recorded, but the statistical analysis plan and these implementation details are not reported in the registry record. The posted information supports a description of the intended comparison, not a reconstruction of the analysis.
10. Multiplicity, Missing Data and Analysis Populations
The record lists one primary endpoint and several secondary outcomes, including time to recurrence, progression rate at 2 years, time to progression, number of recurrences per patient, disease-free interval, disease-free survival, and overall survival. Testing multiple outcomes can increase the chance of finding at least one apparently unusual result by chance if each is interpreted as a separate confirmatory test. General approaches to multiplicity include prespecifying a testing hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, testing hierarchy, or whether secondary outcomes were intended as confirmatory.
The primary outcome entry is not reduced to a single comparison, and the record does not report a consolidated arm-to-arm estimate for recurrence at 2 years. The registry record also does not report the statistical analysis plan, the primary hypothesis test, a primary confidence interval, or the handling of multiple analyses. Without those details, the inferential status of any outcome should not be inferred from its listing alone.
Missing data can affect a fixed-time recurrence analysis if participants lack sufficient follow-up or outcome assessment. General methods may include assumptions about the missingness process, censoring, or imputation, and different choices can produce different estimates. The registry record does not report how missing recurrence assessments were handled, the extent of missing primary outcome data, or sensitivity analyses. It also does not identify the analysis population for the primary endpoint, such as whether all randomized participants were included or whether eligibility confirmation affected inclusion. The amount and potential impact of missing data therefore cannot be evaluated from the record.
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 |
|---|---|---|---|
| Apaziquone | 93 | 406 | 22.9% |
| Placebo | 98 | 396 | 24.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Apaziquone | 11 of 406 |
| Placebo | 13 of 396 |
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 |
|---|---|
| Apaziquone | 312 of 406 |
| Placebo | 285 of 396 |
Most frequent serious adverse event terms
| Event term | Organ system | Apaziquone | Placebo |
|---|---|---|---|
| Hematuria | Renal and urinary disorders | 6 of 406 | 8 of 396 |
| Pneumonia | Infections and infestations | 5 of 406 | 7 of 396 |
| Cardiac Failure Congestive | Cardiac disorders | 5 of 406 | 6 of 396 |
| Chest Pain | General disorders | 5 of 406 | 4 of 396 |
| Chronic Obstructive Pulmonary Disease | Respiratory, thoracic and mediastinal disorders | 5 of 406 | 4 of 396 |
| Coronary Artery Disease | Cardiac disorders | 3 of 406 | 6 of 396 |
| Cellulitis | Infections and infestations | 5 of 406 | 3 of 396 |
| Knee Arthroplasty | Surgical and medical procedures | 3 of 406 | 4 of 396 |
| Urinary Tract Infection | Infections and infestations | 2 of 406 | 5 of 396 |
| Atrial Fibrillation | Cardiac disorders | 6 of 406 | 0 of 396 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Apaziquone | Placebo |
|---|---|---|---|
| Dysuria | Renal and urinary disorders | 74 of 406 | 67 of 396 |
| Urinary tract infection | Infections and infestations | 70 of 406 | 58 of 396 |
| Haematuria | Renal and urinary disorders | 38 of 406 | 57 of 396 |
| Pollakiuria | Renal and urinary disorders | 39 of 406 | 46 of 396 |
| Micturition urgency | Renal and urinary disorders | 31 of 406 | 37 of 396 |
| Procedural pain | Injury, poisoning and procedural complications | 31 of 406 | 27 of 396 |
| Bladder spasm | Renal and urinary disorders | 29 of 406 | 23 of 396 |
| Urinary retention | Renal and urinary disorders | 17 of 406 | 30 of 396 |
| Bladder pain | Renal and urinary disorders | 22 of 406 | 18 of 396 |
| Nausea | Gastrointestinal disorders | 16 of 406 | 19 of 396 |
Serious events with the highest arm-level rate: hematuria (2.0%), pneumonia (1.8%), cardiac failure congestive (1.5%), coronary artery disease (1.5%), atrial fibrillation (1.5%).
The registry lists adverse-event information separately for the apaziquone and placebo groups. For serious adverse events, the recorded at-risk counts are 406 for apaziquone and 396 for placebo; the affected-participant counts are 93 and 98, respectively. For other adverse events, the recorded at-risk counts are 406 and 396, and the affected-participant counts are 312 and 285. These are counts of participants, not rates calculated for comparison. Deaths are listed as 11 and 13, respectively; the record does not state in this entry whether these deaths were considered treatment-related.
The registry also lists selected serious adverse-event terms with percentages: Hematuria, 2.0%; Pneumonia, 1.8%; Cardiac Failure Congestive, 1.5%; Coronary Artery Disease, 1.5%; Atrial Fibrillation, 1.5%; and Urinary Tract Infection, 1.3%. These listed terms describe reported events and do not by themselves establish causation or a between-group difference. The record does not provide the event-specific group breakdown in this list, nor does it explain whether participants could contribute more than one event. Serious-event counts, other-event counts, selected terms, and deaths are distinct summaries and should not be combined as though they measure the same outcome.
12. What the Result Does, and Does Not, Mean
The record establishes the clinical question, intervention, comparator, trial design, and definition of the primary recurrence outcome. It identifies a randomized, placebo-controlled, double-blind phase 3 comparison of a single intravesical dose of apaziquone after TURBT against placebo after TURBT. It also specifies that the primary question concerns histologically confirmed recurrence by year 2 in a defined Ta, G1-G2 population.
What the record does not establish is the primary treatment effect. It does not provide a single arm-to-arm recurrence estimate, the corresponding event counts, a confidence interval, or a test result for the primary comparison. Accordingly, it cannot support a conclusion about whether recurrence was more or less frequent in either group, nor about the size or precision of any difference. The stated purpose of the study should not be mistaken for a finding.
The safety summaries provide counts of participants with serious and other adverse events, deaths, and selected serious-event terms. They are useful descriptions of what the registry lists, but they do not establish that an event was caused by apaziquone or that the groups differed. Such conclusions would require suitable comparative analyses and fuller event context, neither of which is provided in these summaries.
Statistical interpretation also depends on who contributed primary outcome data, how missing assessments were handled, which effect measure and model were used, and whether analyses were prespecified. These details are not reported in the registry record. The study’s completed status and enrollment figure do not fill those gaps. The sound interpretation is therefore limited to what is documented: a well-defined randomized comparison was undertaken, while the primary numerical result and key analysis details are unavailable in the registry entry.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its registry record separates the existence of a clearly framed clinical question from the availability of an interpretable numerical answer. A randomized comparison, a defined control group, masking, and a prespecified-looking fixed-time endpoint are important components of a trial design. Yet those features do not substitute for arm-specific outcome data and an estimate of the treatment contrast.
The primary outcome definition also illustrates why endpoint details matter. The event required histological confirmation, was limited to a stated follow-up window, and applied to a defined Ta, G1-G2 population with restrictions on tumor number and size. Those conditions determine what counts as a primary event and who belongs to the target population. A result for a broader group or a different time window would not automatically answer the same question.
The record further illustrates the distinction between outcome domains. A fixed-time recurrence measure, time to recurrence, progression outcomes, and safety summaries each address different questions. Their existence in the registry does not make their results interchangeable. In particular, adverse-event counts cannot stand in for recurrence results, and a list of secondary outcomes cannot reveal whether multiplicity was addressed.
Finally, planning illustrations based on an observed effect should be kept separate from the trial’s original design rationale and from observed treatment evidence. They can help show how assumptions about effect size and design relate to planning, but they are not observed power and do not replace the primary estimate. The record is a reminder that statistical interpretation requires both a defined question and transparent reporting of the analysis and its uncertainty.
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 this trial statistically is that the registry record does not report a single primary comparison for recurrence at 2 years. The endpoint definition is detailed, but arm-specific recurrence counts, an effect estimate, an uncertainty interval, and a test result are not reported in the primary outcome entry. This prevents assessment of the magnitude, direction, and precision of the primary result.
The primary analysis population is not described. The registry defines a Target Ta, G1-G2 population with limits on tumor number and size and central pathology confirmation, but does not report how many participants met those conditions or how eligibility confirmation was incorporated into analysis. Enrollment of 802 does not establish the number contributing to the endpoint. The record also does not report participant flow, exclusions, withdrawals, or outcome completeness.
Methods that affect interpretation are not reported in the registry record, including the primary effect measure, statistical model or test, missing-data approach, and sensitivity analyses. The record also does not describe the multiplicity strategy across the listed secondary outcomes. These omissions make it impossible to evaluate robustness or determine how the reported analysis, if any, addressed uncertainty and multiple comparisons.
The safety information is presented as group counts and selected serious-event terms, without enough detail to assess event-specific comparative risks or causal attribution. The registry record does not provide the protocol’s sample-size justification or explain whether the planning illustrations reflect original design assumptions. These limitations are specific to the information recorded and do not establish that analyses or documentation were absent elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Single Dose Intravesical Apaziquone Postoperative in Patients Undergoing TURBT for Noninvasive Bladder Cancer (SPI-611) — NCT00461591.
- Registry record last updated 2021-03-30; status last verified 2021-03.
- Results first posted 2017-08-15.
- 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.
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
The registry record describes a completed, randomized, placebo-controlled, double-blind phase 3 parallel-group trial of TURBT plus a single intravesical apaziquone dose versus TURBT plus placebo for noninvasive bladder cancer. The listed enrollment is 802. The primary outcome is histologically confirmed recurrence by year 2 in the Target Ta, G1-G2 population, with limits on tumor number and size and central pathology confirmation.
Secondary outcomes include recurrence timing, progression, recurrence counts, disease-free outcomes, and overall survival. The registry lists adverse-event counts, deaths, and selected serious adverse-event terms. However, it does not report a single arm-to-arm primary recurrence estimate or the analysis details needed to assess its precision. The record therefore supports a description of the trial question and design, but not a statistical conclusion about the primary comparison.