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 A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT) (NCT02563561), a randomized phase 3 study. The primary outcome is Time to Recurrence.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02563561 |
| Phase | Phase 3 |
| Condition | Bladder Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 62 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Spectrum Pharmaceuticals, Inc |
| Results posted | Yes |
2. Clinical Question
Population
Participants had non-muscle invasive bladder cancer (NMIBC), with no more than 4 tumors and a maximum tumor diameter of 3.5 cm. All tumors had to be fully resected at transurethral resection of bladder tumor (TURBT). The registry summary also describes cystoscopic assessment for clinically apparent Ta, G1-G2 disease. Further eligibility details are not reported in the registry record.
Intervention
One arm received one 4 mg intravesical apaziquone dose after TURBT, followed by placebo. A second arm received two 4 mg intravesical apaziquone doses. The first dose was administered 60 ± 30 minutes after TURBT on Day 1. The registry record describes administration into the bladder.
Comparator
The comparator arm received matching placebo. Participants were randomized among the three arms in a 1:1:1 ratio. The record describes a multicenter, placebo-controlled trial.
Primary question
The trial planned to evaluate time to histologically confirmed bladder cancer recurrence after TURBT, comparing one apaziquone instillation and two instillations with placebo. The primary outcome was not collected because the study was terminated early. The registry record therefore does not report the comparative recurrence results needed to answer this question.
3. Trial Design
The registry identifies NCT02563561 as a Phase 3 randomized trial of intravesical apaziquone as a surgical adjuvant after TURBT for NMIBC. The official title describes a multicenter, multi-arm, randomized, multi-dose, placebo-controlled, double-blind study; the registry design fields identify triple masking and a parallel model. The record therefore uses both double-blind wording in its summary and a triple-masking classification in its design information.
Participants were randomized in a 1:1:1 ratio to one dose of apaziquone, two doses of apaziquone, or placebo. The one-dose arm received 4 mg apaziquone followed by placebo. The two-dose arm received 4 mg apaziquone twice. The comparator arm received matching placebo. The first administration was intravesical and scheduled 60 ± 30 minutes after TURBT on Day 1. The record describes the study as placebo controlled and parallel group, so the treatment arms were intended to be evaluated as separate groups rather than as a crossover sequence.
The registry reports enrollment of 62 and lists the study status as terminated. The recorded start date is 2015-10-09, and the primary completion date is 2017-03-10. The reason for termination is not reported in the registry record. The planned primary endpoint was time to recurrence, with a stated observation timeframe of up to 1.5 years. The registry explicitly says that data for this outcome were not collected because of early termination.
The record does not describe the randomization method, allocation concealment, the operational details of masking, treatment adherence, or the planned analysis population. Although the trial had three randomized arms and described comparisons with placebo, its primary recurrence results are unavailable in the registry record. This means the planned efficacy question cannot be evaluated from the posted primary outcome data.
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.
Before assignment: A total of 62 participants were randomized into the study, out of which 6 participants completed the study.
Overall Study
| Stage | 1 Dose Apaziquone | 2 Dose Apaziquone | Placebo |
|---|---|---|---|
| STARTED | 19 | 23 | 20 |
| Safety Population | 19 | 21 | 17 |
| COMPLETED | 1 | 2 | 3 |
| NOT COMPLETED | 18 | 21 | 17 |
Reasons for not completing this period:
| Reason | 1 Dose Apaziquone | 2 Dose Apaziquone | Placebo |
|---|---|---|---|
| Histology Other than Ta, G1-G2 | 3 | 6 | 6 |
| Withdrew of Consent | 1 | 1 | 2 |
| Lost to Follow-up | 1 | 1 | 0 |
| Participant Had Recurrence and Received Therapy | 4 | 2 | 1 |
| Investigator Decision | 3 | 4 | 2 |
| Sponsor Decision | 5 | 2 | 4 |
| Other | 1 | 5 | 2 |
Analysis population for the primary outcome, as defined in the registry: Data for this outcome measure was not collected due to early termination of study.
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 Population included all randomized participants classified according to the actual treatment received, regardless of random assignment.
| Characteristic | Unit | 1 Dose Apaziquone | 2 Dose Apaziquone | Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 19 | 21 | 17 | 57 | |
| Age, Continuous | years | 67.5 (SD 9.2) | 66.6 (SD 12.4) | 66.1 (SD 12.4) | 66.7 (SD 11.2) |
| Sex: Female, Male: Female | Participants | 5 | 7 | 6 | 18 |
| Sex: Female, Male: Male | Participants | 14 | 14 | 11 | 39 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 3 | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 18 | 21 | 14 | 53 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 0 | 2 |
| Race (NIH/OMB): White | Participants | 18 | 20 | 17 | 55 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Recurrence, measured over From randomization to the date of first histologically confirmed recurrence of bladder cancer (up to 1.5 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 time from randomization to the date of the first histologically confirmed recurrence of bladder cancer. Recurrence was defined as pathologically confirmed disease of ≥Ta tumor histology or carcinoma in situ (CIS) after treatment. The stated timeframe was up to 1.5 years.
Time-to-event endpoints retain information about when an event occurs, rather than recording only whether an event occurred by a selected follow-up point. In general, this can be useful when participants have different lengths of observation or when the timing of recurrence is clinically relevant. The interpretation depends on reliable event ascertainment and adequate follow-up, along with a specified approach to participants whose event status is not observed through the end of follow-up.
In this trial, the registry says the primary outcome was not collected because of early termination. It therefore reports no recurrence times, event counts, treatment effect estimate, confidence interval, or primary-outcome comparison. The planned endpoint definition clarifies what the trial intended to measure, but it does not establish what happened to participants or how the treatment arms compared.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the planned primary outcome is unavailable. The registry states that time-to-recurrence data were not collected because the study was terminated early. Without those data, there is no posted estimate of recurrence timing for any arm and no comparative estimate for one or two apaziquone doses versus placebo. The clinical question posed by the primary endpoint therefore remains unanswered by the registry results.
The record does include safety counts. Serious adverse events were reported for 0 of 19 participants in the one-dose apaziquone arm, 2 of 21 in the two-dose apaziquone arm, and 1 of 17 in the placebo arm. Other adverse events were reported for 10 of 19, 12 of 21, and 7 of 17, respectively. Deaths were reported as 0 in each arm. These are descriptive counts; they do not substitute for the missing recurrence outcome, nor do they by themselves establish that one arm is safer or less safe.
In general, observed counts reflect both the event experience and the amount of information available. Small groups can yield imprecise estimates, and a count alone does not communicate uncertainty. The registry record does not provide confidence intervals or comparative statistical tests for the adverse event summaries. No adjusted or unadjusted effect estimates for these safety outcomes are reported in the registry record. It would therefore be inappropriate to interpret the numerical differences between the posted counts as evidence of a treatment effect.
The serious-event term list includes Large Intestine Perforation at 5.9%, Large Intestinal Stenosis at 5.9%, Bladder Perforation at 4.8%, and Colitis Ischaemic at 4.8%. The registry does not specify in this listing which treatment arm each term belongs to or provide the denominator for these percentages. These term-level percentages should not be used to infer an arm-specific risk or to compare groups.
The trial is listed as terminated, but the reason for termination is not reported in the registry record. The record does not explain whether termination was related to recruitment, operational considerations, safety, efficacy, or another cause. No such explanation should be inferred from the absence of primary outcome data. Taken together, the posted information describes the design and some adverse-event counts, but it does not provide a basis for drawing a comparative conclusion about recurrence or treatment effects.
9. Statistical Methods Explained
Several statistical ideas help clarify what the record can and cannot establish. The explanations below are general; they describe concepts rather than analyses reported for this trial.
What does randomization contribute?
In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment, including differences that may not be measured. It does not guarantee that groups will be identical, particularly when group sizes are limited. A 1:1:1 allocation ratio was planned for this study, with assignment to one apaziquone dose, two apaziquone doses, or placebo. The exact randomization sequence and allocation-concealment procedures are not reported in the registry record.
Randomization supports a fair comparison when outcomes are collected and analyzed according to appropriate methods. It cannot compensate for an outcome that was not collected. Since the primary recurrence outcome is absent, randomization alone cannot yield an estimate of the effect on time to recurrence.
How is a time-to-event outcome interpreted?
In general, a time-to-event analysis uses both whether an event occurs and the time until it occurs. The planned event in this trial was first histologically confirmed recurrence, defined as disease of ≥Ta tumor histology or CIS after treatment. Time began at randomization. A time-to-event analysis can use information from participants who have not had a recorded event by their last observation, but that requires a clear record of follow-up and a specified censoring approach. Censoring means that the exact event time is not observed during the available follow-up; it does not mean that the event can be assumed never to occur.
The registry record does not report recurrence observations, censoring information, a survival curve, a hazard ratio, or another time-to-event estimate. It also does not report the planned statistical model or the assumptions that would have supported such a model. The endpoint definition and timeframe describe the intended measurement, not a completed time-to-event analysis.
What does a confidence interval communicate?
In general, a confidence interval describes the statistical uncertainty around an estimated quantity under a specified method. A narrow interval indicates greater precision than a wide interval, while an interval spanning a broad range of possible effects indicates that the estimate is less informative. An interval does not correct bias, make missing outcomes available, or prove that an effect is absent when a comparison is not statistically significant. No confidence interval for the primary outcome is reported in the registry record, because the primary outcome was not collected.
Why do event counts need context?
In general, counts are easiest to interpret when the event definition, observation period, denominator, and method of collection are clear. Counts can describe what was recorded but do not alone quantify a comparative effect or its uncertainty. This matters for the adverse-event information: the registry provides arm-level counts for serious and other adverse events, but it does not report comparative estimates or uncertainty intervals for them. The listed serious-event terms and percentages also lack an arm-specific attribution in the registry record.
Over-dispersion is a general statistical concern when event variability exceeds what a chosen model expects. If a model assumes less variability than is present, its uncertainty estimates may be too small and its conclusions too confident. No count model, dispersion assessment, or comparative adverse-event analysis is reported for this trial, so over-dispersion cannot be assessed from the registry entry.
What can planning calculations say?
In general, sample-size calculations are planning tools. They depend on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. They do not show that an effect was observed, and a planned sample size does not guarantee precise results if the study ends early or outcomes are unavailable. The registry's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These assumptions describe a planning illustration; they do not document the trial's own design justification.
The registry record does not report a sample-size justification for the trial or a completed primary-outcome estimate from which to interpret a recurrence effect. Any planning illustration must be distinguished from observed evidence. It is not observed power and cannot compensate for missing primary outcome data.
What do the design labels establish?
The record identifies the study as randomized, parallel, placebo controlled, and Phase 3. It also labels masking as triple, while the study summary uses double-blind wording. Those labels describe the recorded design but do not provide every operational detail. The registry record does not explain which people were masked, how masking was maintained, or whether it was assessed. Such details matter when considering possible influence on treatment delivery, outcome ascertainment, and reporting, but should not be guessed.
Overall, the methods-related information establishes the intended randomized comparison and the definition of the primary endpoint. It does not establish that a comparative efficacy analysis was completed. The distinction is important: a planned statistical method, a design label, or a planning assumption is not itself an observed treatment effect.
10. Multiplicity, Missing Data and Analysis Populations
The trial included three arms: one dose of apaziquone, two doses of apaziquone, and placebo. The registry summary describes the primary objective as evaluating each apaziquone regimen relative to placebo. When a study examines more than one treatment comparison or multiple outcomes, multiplicity can arise. In general, making several statistical comparisons can increase the chance of at least one apparently significant result if the analysis does not account for the number and structure of tests.
The registry record does not report a multiplicity adjustment, a hierarchy for testing the two apaziquone comparisons, or a detailed statistical analysis plan. It does not report outcome analyses for the primary endpoint. No conclusion about how multiplicity would have been handled can be drawn from the design description alone.
Missing data are central to interpretation because the registry states that the primary outcome was not collected due to early termination. It does not give participant-level follow-up, the amount or pattern of missing recurrence information, or any imputation or sensitivity-analysis approach. The reason for early termination is also not reported in the registry record. These gaps prevent assessment of whether missingness could have been related to prognosis, treatment assignment, or practical follow-up circumstances.
The registry record does not identify an intention-to-treat, per-protocol, or other analysis population for the primary endpoint. It also lists no outcome analyses. The arm-level adverse-event counts are available, but the record does not describe their analysis population or provide an inferential comparison. Accordingly, the available entry supports a description of design and recorded safety counts, not a reconstruction of the intended efficacy analysis or its handling of multiplicity and missing outcomes.
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 |
|---|---|---|---|
| 1 Dose Apaziquone | 0 | 19 | 0.0% |
| 2 Dose Apaziquone | 2 | 21 | 9.5% |
| Placebo | 1 | 17 | 5.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 1 Dose Apaziquone | 0 of 19 |
| 2 Dose Apaziquone | 0 of 21 |
| Placebo | 0 of 17 |
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 |
|---|---|
| 1 Dose Apaziquone | 10 of 19 |
| 2 Dose Apaziquone | 12 of 21 |
| Placebo | 7 of 17 |
Most frequent serious adverse event terms
| Event term | Organ system | 1 Dose Apaziquone | 2 Dose Apaziquone | Placebo |
|---|---|---|---|---|
| Bladder Perforation | Renal and urinary disorders | 0 of 19 | 1 of 21 | 0 of 17 |
| Colitis Ischaemic | Gastrointestinal disorders | 0 of 19 | 1 of 21 | 0 of 17 |
| Large Intestine Perforation | Gastrointestinal disorders | 0 of 19 | 0 of 21 | 1 of 17 |
| Large Intestinal Stenosis | Gastrointestinal disorders | 0 of 19 | 0 of 21 | 1 of 17 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 1 Dose Apaziquone | 2 Dose Apaziquone | Placebo |
|---|---|---|---|---|
| Dysuria | Renal and urinary disorders | 4 of 19 | 7 of 21 | 2 of 17 |
| Bladder Spasm | Renal and urinary disorders | 2 of 19 | 4 of 21 | 0 of 17 |
| Haematuria | Renal and urinary disorders | 1 of 19 | 3 of 21 | 1 of 17 |
| Bladder Pain | Renal and urinary disorders | 2 of 19 | 2 of 21 | 0 of 17 |
| Micturition Urgency | Renal and urinary disorders | 2 of 19 | 0 of 21 | 1 of 17 |
| Nocturia | Renal and urinary disorders | 0 of 19 | 2 of 21 | 1 of 17 |
| Adrenal Mass | Endocrine disorders | 1 of 19 | 1 of 21 | 0 of 17 |
| Nausea | Gastrointestinal disorders | 1 of 19 | 1 of 21 | 0 of 17 |
| Fatigue | General disorders | 0 of 19 | 1 of 21 | 1 of 17 |
| Headache | Nervous system disorders | 2 of 19 | 0 of 21 | 0 of 17 |
Serious events with the highest arm-level rate: large intestine perforation (5.9%), large intestinal stenosis (5.9%), bladder perforation (4.8%), colitis ischaemic (4.8%).
The registry reports serious adverse events in 0 of 19 participants in the 1 Dose Apaziquone arm, 2 of 21 in the 2 Dose Apaziquone arm, and 1 of 17 in the placebo arm. Other adverse events were reported in 10 of 19, 12 of 21, and 7 of 17, respectively. Deaths were reported as 0 in all three arms.
These figures are counts of participants reported as affected, not a complete description of the type, timing, duration, severity, or clinical course of every event. The registry record does not provide comparative confidence intervals or statistical tests for these summaries, and it does not explain whether follow-up was comparable across arms. The counts alone therefore do not establish that the regimens differ in safety.
The registry lists Large Intestine Perforation at 5.9%, Large Intestinal Stenosis at 5.9%, Bladder Perforation at 4.8%, and Colitis Ischaemic at 4.8% among the serious-event terms. The listing does not identify an arm-specific denominator or connect each term to a particular arm. These percentages should be read as registry-listed term figures, not as comparative risks. The reason for study termination is not reported in the registry record, so the termination should not be attributed to these events or to any other cause.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, placebo-controlled Phase 3 study was planned to compare one and two intravesical apaziquone doses with placebo after TURBT. It defines the primary endpoint as time from randomization to first histologically confirmed recurrence and supplies the recurrence definition. It also records arm-level safety counts and identifies the study as terminated.
The record does not establish whether either apaziquone regimen changed recurrence risk or delayed recurrence. The primary outcome was not collected because of early termination, and no treatment effect estimate, uncertainty interval, or comparative recurrence analysis is reported. The planned endpoint definition cannot be treated as an outcome result. The trial's randomized design also cannot answer the primary question without the corresponding outcome observations.
The adverse-event counts provide limited descriptive information. They are not a substitute for the missing efficacy endpoint and, without comparative estimates and further context, do not establish that one treatment regimen has a different safety profile from another. The registry-listed serious-event percentages are not assigned to treatment arms in the available record.
These limitations do not show that apaziquone was effective or ineffective, nor do they establish that it was safe or unsafe. They describe the limits of the posted record. The reason for termination, the statistical plan, the intended analysis population, and the handling of missing data are not reported in the registry record. Any interpretation should keep the distinction between an intended clinical question, descriptive safety information, and a completed comparative analysis clear.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction in clinical research: a well-defined design and endpoint are not the same as an analyzable result. The registry describes a randomized comparison of two apaziquone dosing strategies with placebo, and it specifies a time-to-recurrence endpoint with a histological definition. Yet it also states that the primary outcome was not collected because the study ended early. Consequently, the central comparative question cannot be answered from the posted results.
For biostatisticians and clinical researchers, this record highlights why outcome availability, follow-up, and analysis planning are essential to interpretation. Randomization is valuable because it is intended to support fair group comparisons, but it does not generate evidence when the planned endpoint is unavailable. Similarly, a stated timeframe and event definition describe what investigators intended to measure; they do not reveal event frequency or timing.
The record also demonstrates the limits of descriptive safety counts. Such counts can document events recorded in the study, but without context, uncertainty estimates, and a clear comparative analysis they should not be read as proof of a treatment difference. Term-level percentages without an arm attribution have still more limited comparative meaning.
Finally, the registry's termination status and missing primary outcome make transparent reporting especially consequential. The reason for termination and key analysis details are not reported in the registry record. Statistical interpretation must therefore remain bounded by the information that is available: the study design, the endpoint that was planned, the safety counts that were posted, and the absence of primary recurrence data.
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 trial-specific limitation is that the registry says the primary time-to-recurrence outcome was not collected because of early termination. There are no posted recurrence event times, arm-level recurrence results, or comparative effect estimates. The planned observation timeframe of up to 1.5 years cannot be assumed to describe the follow-up actually achieved.
The reason for termination is not reported in the registry record. The entry does not explain whether the reason was operational, related to recruitment, related to safety, related to efficacy, or otherwise. It also does not describe the randomization procedure, allocation concealment, operational masking details, treatment adherence, or the analysis population. The summary calls the study double blind, while the design field identifies triple masking; the registry does not explain the difference in terminology.
Important analysis details are also absent. The registry record does not report a detailed statistical plan, an approach to multiplicity, methods for missing data, or a primary-outcome analysis. It does not provide confidence intervals or inferential comparisons for the posted adverse-event counts. The serious-event term percentages are not linked to treatment arms or accompanied by denominators in the listing.
These limitations constrain interpretation but do not reveal why the study ended or what the missing recurrence results would have shown. The posted record supports description of the planned design and the available safety counts, but not a conclusion about comparative recurrence outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Intravesical Apaziquone as a Surgical Adjuvant in Participant Undergoing Transurethral Resection Bladder Tumor (TURBT) — NCT02563561.
- Registry record last updated 2021-10-27; status last verified 2021-10.
- Results first posted 2021-09-27.
- 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
NCT02563561 was a randomized, parallel, placebo-controlled Phase 3 study of intravesical apaziquone after TURBT for NMIBC. Participants were assigned to one apaziquone dose, two apaziquone doses, or placebo in a 1:1:1 ratio. The registry reports enrollment of 62 and lists the study as terminated.
The primary endpoint was time from randomization to first histologically confirmed recurrence, defined as disease of ≥Ta tumor histology or CIS after treatment. The registry states that this outcome was not collected because of early termination. The reason for termination and the planned analysis details are not reported in the registry record.
Arm-level counts for serious adverse events, other adverse events, and deaths are available, but comparative safety estimates are not reported. The record therefore describes the intended trial question and some safety information without providing the primary recurrence results required to assess the planned treatment comparisons.