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 Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer (NCT03498196), a na phase 1, phase 2 study. The primary outcome is Change in T Cell Subpopulations.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03498196 |
| Phase | Phase 1, Phase 2 |
| Condition | Bladder Cancer, Metastatic Bladder Cancer, Invasive Bladder Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Baylor College of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Patients with non-metastatic, muscle invasive bladder cancer who were eligible for radical cystectomy but ineligible for cisplatin-based neoadjuvant therapy. The study enrolled one patient; its target was 10 evaluable patients.
Intervention
Avelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days, before surgery.
Comparator
There was no concurrent comparator group. The study is recorded as single-group and non-randomized, so its design does not support a like-for-like treatment comparison.
Primary question
The planned primary outcome was the change in tumor T-cell subpopulations, including CD8, CD4 and/or CD3, between pre-study tissue and tissue collected after the operation. No assay was done.
This was described as a window of opportunity pilot study. In this type of setting, treatment is given during the period before planned surgery, and paired tumor specimens are intended to permit measurement before and after treatment. The registry describes the pre-study specimen as tissue from transurethral resection of the bladder tumor and the post-operation specimen as tissue from radical cystectomy. The primary outcome timeframe is pre-study time and 2-3 week post-operation.
The clinical question was therefore about a tumor-tissue measurement after avelumab exposure, not a comparison of clinical outcomes between treatment groups. Secondary outcomes listed in the record were pathological response rate, 2 Year Disease Free Survival (DFS), and rate of high grade (Grade 3-4) adverse events. The record does not provide results for these outcomes. With one patient enrolled and no primary assay performed, the registry record cannot establish a group-level change in T-cell subpopulations or characterize clinical outcomes across the intended population.
3. Trial Design
The registry classifies this as a phase 1 and phase 2, single-group study with no masking and no randomized allocation. It lists avelumab as the intervention. The planned treatment was avelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days. The study was intended for patients with non-metastatic, muscle invasive bladder cancer who could undergo radical cystectomy but were ineligible for cisplatin-based neoadjuvant therapy.
The study began on 2018-12-14, had a primary completion date of 2019-12-09, and is recorded as terminated. Enrollment was 1. The brief summary states that the target recruitment was 10 evaluable patients. The difference between the intended target and the recorded enrollment means that the planned pilot did not accrue the target number of evaluable patients. The registry does not report why the study was terminated or why enrollment stopped.
The planned primary assessment used tumor tissue from transurethral resection before treatment and tissue from radical cystectomy after treatment. The recorded post-operation timeframe is 2-3 week post-operation. However, the registry states that the assay was planned after enrolling several patients and collecting specimens, but only one patient was enrolled and no assay was done. Thus, the intended paired-tissue design did not yield a primary outcome measurement.
There was no control arm, so the trial was not designed to separate a treatment-associated change from other explanations through a concurrent comparison. The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or details of how planned outcomes would be analyzed. Its enrollment target is reported in the study summary, but no rationale for that target is reported 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 | Avelumab |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The assay for the outcome measure was planned to do after enrolling several patients and collecting specimen but only one patient was enrolled for this study. No assay was done.
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 | Avelumab |
|---|---|---|
| Participants analysed | 1 | |
| Age, Continuous | years | 58 (SD NA) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| 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 | 1 |
| Race (NIH/OMB): White | Participants | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
| Current Smoking | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change in T Cell Subpopulations, measured over pre-study time and 2-3 week post-operation.
| 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 outcome was change in T-cell subpopulations in tumor samples. The record names CD8, CD4 and/or CD3 and specifies that the specimens were formalin-fixed, paraffin-embedded tissue. Tissue from the pre-study time point came from transurethral resection of the bladder tumor; tissue from the post-operation time point came from radical cystectomy. The stated timeframe was pre-study time and 2-3 week post-operation.
In general, measuring immune-cell populations in tumor tissue can describe the cellular composition of a tumor sample and whether that composition differs between sampled time points. A before-and-after measurement is intended to characterize within-patient change. Such a measurement is a biological endpoint; it is not by itself a direct estimate of a treatment effect, especially when no concurrent comparator is included.
The registry explicitly states that the assay was planned after enrolling several patients and collecting specimens, but only one patient was enrolled and no assay was done. Therefore, no value, direction, or magnitude of change in T-cell subpopulations is reported. The record also does not provide the assay procedure, a quantitative definition of the endpoint, or a prespecified rule for combining or interpreting the named cell populations. Those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the primary endpoint was not measured. The registry records one patient enrolled and states that no assay was done for the planned change in T-cell subpopulations. There is consequently no observed primary endpoint estimate, no measure of variability for that endpoint, and no inferential result describing a before-and-after change. The intended target of 10 evaluable patients was not reached according to the recorded enrollment.
The absence of a primary result should not be confused with a result showing no change. A finding of no change would require an actual measurement and a defined analysis; neither is reported. The record therefore cannot tell readers whether the T-cell populations increased, decreased, or remained similar after treatment. It also cannot establish the precision of any such change.
The study had a single group and no randomized allocation. As a general statistical principle, an uncontrolled before-and-after comparison can describe changes over time if both measurements are collected, but it cannot isolate the contribution of treatment from other influences as a controlled comparison can. In this case, even that descriptive paired comparison is unavailable because no assay was performed.
The registry lists pathological response rate, 2 Year Disease Free Survival (DFS), and rate of high grade (Grade 3-4) adverse events as secondary outcomes. It does not report outcome analyses for these endpoints. The absence of reported results should not be converted into a claim that an event did or did not occur, except where the adverse-event figures are specifically recorded. Nor can the listed outcome names establish that complete assessments were available.
The safety summary records one patient at risk and one affected for serious adverse events, other adverse events, and deaths in the Avelumab group. It also lists Sepsis and Urinary tract obstruction among the top serious terms, each reported as 100.0%. These are registry entries from a group with one patient, not stable estimates of event frequency in a broader patient population. The record does not establish the cause of death or provide enough information to make a causal attribution to treatment.
Overall, the posted data describe a study that stopped with limited enrollment and without its planned primary assay. The information is useful for understanding what the study intended to measure and what was recorded, but it does not support an estimate of the primary biological outcome or comparative treatment effects.
9. Statistical Methods Explained
General: what an endpoint estimate would represent. An endpoint estimate is a numerical summary of the outcome measured in the study population. For this trial, the primary endpoint was intended to summarize change in selected T-cell subpopulations between pre-study tumor tissue and post-operation tumor tissue. A paired analysis would use measurements from the same patient at both time points. The exact measurement scale and statistical summary are not reported in the registry record, so the intended estimate cannot be specified more precisely.
The registry says no assay was done. Without endpoint measurements, there is no observed change to summarize and no sample variability from which to estimate uncertainty. A confidence interval, in general, describes a range of values compatible with an estimate under the assumptions of a statistical model. It does not repair the absence of an observed endpoint. No confidence interval for the primary outcome is reported.
General: why a comparator matters. A single-group study can describe observations among participants who received the intervention. If it includes measurements before and after treatment, it may also describe within-person change. But a change over time can have explanations other than the intervention. A concurrent comparator can help distinguish treatment-associated differences from changes that might also occur without the intervention, although the strength of that inference depends on design and analysis. This study is recorded as single-group, with no randomized allocation and no masking. There is no like-for-like control comparison.
The absence of a comparator is particularly important when interpreting any proposed treatment effect. The primary outcome would have been a biological change in tissue, and the secondary outcomes include clinical and safety outcomes. The registry does not report an analysis comparing avelumab with another treatment or with no treatment. No causal contrast between groups is therefore available from the record.
General: precision and small samples. Precision concerns how much uncertainty surrounds an estimate. A small number of observations generally limits the ability to characterize variation, while a missing outcome leaves no estimate at all. Enrollment was 1, whereas the study summary described a target of 10 evaluable patients. This does not provide a basis for estimating the planned population-level endpoint or its precision. It is not appropriate to treat the target as if those participants had been enrolled or measured.
The record includes planning assumptions for illustrative sample-size calculations: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of an observed effect. Time-to-event illustrations use a total number of events, while other illustrations use participants per arm. These assumptions describe planning illustrations, not the study's own design. Since there is no reported primary endpoint result from which to obtain an observed effect, such illustrations cannot be read as evidence about this trial's power or as observed outcomes. The registry record does not report the study's own sample-size justification.
General: over-dispersion and model choice. In count outcomes, over-dispersion means that observed variation exceeds what a simple model assumes. If present, it can make conventional uncertainty estimates too narrow unless the analysis accounts for it. The registry does not report a count-data model or an analysis of over-dispersion for this study. More broadly, the listed primary endpoint concerns tissue subpopulations, but the record does not specify whether those populations would be analyzed as counts, proportions, continuous measurements, or another form. It would be inappropriate to assume a particular model or variance structure.
General: missing outcome data. Missing measurements reduce the information available for analysis. The stated reason the primary assay was not done is that the plan was to perform it after enrolling several patients and collecting specimens, while only one patient was enrolled. The record does not state whether paired specimens were collected from that patient, whether they were adequate for an assay, or whether any other planned endpoint information was available. No imputation method or missing-data sensitivity analysis is reported. Because there is no primary assay result, there is no basis for choosing among statistical methods for handling missing primary measurements.
General: multiplicity. Multiplicity arises when several outcomes or statistical tests are evaluated, increasing the chance that at least one result appears noteworthy by chance if each test is interpreted without adjustment. The registry lists multiple secondary outcomes and names several T-cell subpopulations in the primary outcome description. It does not report a hierarchy of tests, an adjustment for multiple comparisons, or how the primary measures would be combined. This means the planned approach to multiplicity is not reported in the registry record; no claim about whether multiplicity was controlled is warranted.
There are no analyses reported in the registry. In practical terms, readers have study design and outcome definitions, but not an inferential analysis of the planned primary endpoint. The registry does not report an analysis population definition, a statistical plan, or estimates with uncertainty for the listed outcomes. The correct interpretation is therefore descriptive of the study's conduct and reporting status, not a reanalysis of a completed endpoint dataset.
10. Multiplicity, Missing Data and Analysis Populations
The record names a primary outcome involving CD8, CD4 and/or CD3 T-cell subpopulations, as well as secondary outcomes of pathological response rate, 2 Year Disease Free Survival (DFS), and rate of high grade (Grade 3-4) adverse events. Evaluating several outcomes or several components of an outcome raises multiplicity questions. In general, multiplicity matters because repeated statistical testing can increase the chance of an apparently unusual result when no adjustment or prespecified hierarchy is used.
The registry does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment across tests. It also does not report how the named T-cell subpopulations would be combined or evaluated separately. As no assay or outcome analyses are reported, there are no results for which an adjustment could be assessed.
The primary assay was not done. The registry explains that assay work was planned after enrolling several patients and collecting specimens, but only one patient was enrolled. The record does not state whether specimens were collected or usable, and it does not describe imputation, sensitivity analyses, or another method for addressing missing measurements. An unperformed assay is not a measured zero and cannot be interpreted as no biological change.
The record does not report definitions of the analysis populations, such as which participants would be included in each endpoint analysis, or a statistical analysis plan. Enrollment is recorded as 1, but the intended target was 10 evaluable patients. These registry entries do not establish which participants would have been considered evaluable or how incomplete observations would have been handled. The analytic approach to missing data and the analysis populations are not reported in the registry 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 |
|---|---|---|---|
| Avelumab | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Avelumab | 1 of 1 |
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 |
|---|---|
| Avelumab | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Avelumab |
|---|---|---|
| Sepsis | Infections and infestations | 1 of 1 |
| Urinary tract obstruction | Renal and urinary disorders | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Avelumab |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 1 of 1 |
| Creatinine increased | Investigations | 1 of 1 |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | 1 of 1 |
Serious events with the highest arm-level rate: sepsis (100.0%), urinary tract obstruction (100.0%).
The Avelumab group safety summary records one patient at risk for serious adverse events and one affected. It also records one at risk and one affected for other adverse events, and one at risk and one death. The top serious-event terms are Sepsis and Urinary tract obstruction, each listed as 100.0%.
These figures should be read in the context of the recorded enrollment of one patient. The listed percentages are not precise estimates of event frequency in a larger population; a single patient's experience has a large influence on any percentage calculated from such a small group. The registry does not provide further detail in the registry record reported about event timing, severity beyond the serious-event classification, or the relationship of each event to treatment.
The death entry does not establish that avelumab caused the death, and the record does not state the cause of death. Similarly, the serious-event terms should be reported as recorded rather than interpreted as evidence of a causal relationship. These safety entries describe the registry's recorded counts; they do not support a comparative safety assessment because there was no control group.
12. What the Result Does, and Does Not, Mean
The main result is a limitation of the available evidence: the trial enrolled one patient, and the planned primary assay was not done. Therefore, the registry record contains no measured change in tumor T-cell subpopulations. It does not show that the T-cell populations changed, and it does not show that they did not change. The intended primary biological question remains unanswered in the reported record.
The study was designed as a single-group window of opportunity pilot. Its goal was to examine tumor tissue before and after avelumab in patients proceeding to radical cystectomy who were ineligible for cisplatin-based neoadjuvant therapy. That design describes the setting and intended measurement, but without a comparator it would not, by itself, distinguish treatment effects from other explanations for a before-and-after difference.
The secondary outcomes are listed, but the registry does not report results for them in the registry record for this analysis. The safety summary records adverse events and a death for the one-patient group, but it does not establish causation or allow a stable estimate of risk. Neither the absence of a reported efficacy result nor the limited safety summary should be treated as a general conclusion about avelumab.
In general, a pilot study can be informative about feasibility and can generate data for later research, but interpreting outcomes requires measured endpoints and enough information to assess uncertainty. Here, the planned T-cell assay was not performed, and enrollment did not reach the stated target. The record does not report why the trial terminated, a statistical analysis plan, or a sample-size justification. The evidence therefore supports describing the study's intended question and its limited recorded results, not making claims about treatment benefit, lack of benefit, or comparative safety.
13. Why This Trial Matters Statistically
This study illustrates why registry status and outcome measurement need to be considered together. The record describes a clearly specified biological question: whether tumor T-cell subpopulations would differ between tissue collected before treatment and tissue collected after operation. But because the assay was not done, the question has no reported endpoint estimate. A detailed outcome definition cannot substitute for measured data.
It also highlights the distinction between a recruitment target and actual enrollment. The study summary states a target of 10 evaluable patients, while the recorded enrollment is 1. That gap matters statistically because the intended descriptive and inferential summaries depend on observed participants and measurements, not the planned target. The target does not establish that the study had a particular level of precision or that an analysis could be completed.
The single-group design is another important feature. Without a comparator, any completed before-and-after analysis would have described change within participants rather than a randomized contrast. General causal interpretation would therefore have required caution even if the primary assay had been performed. In this record, the absence of assay results makes even the within-patient description unavailable.
Finally, the safety counts show why percentages from a very small group must be interpreted in context. A percentage can look definitive while representing very few observations. Reporting counts, denominator context, and uncertainty is important for avoiding overstatement. The record offers a useful example of how a trial can document its intended design and outcomes while still leaving its main statistical question unanswered.
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 primary limitation is that the assay for the primary outcome was not done. Consequently, there is no reported measurement of change in T-cell subpopulations and no estimate or uncertainty interval for that outcome. Enrollment was 1, below the target of 10 evaluable patients stated in the study summary.
The registry records a single-group, non-randomized design with no masking and no comparator. Even if the planned tissue measurements had been completed, this design would not provide a randomized comparison against another group. The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or the rationale for termination.
The primary outcome description names CD8, CD4 and/or CD3, but does not provide a quantitative definition or assay details. The record does not state whether paired specimens were collected from the enrolled patient or whether they were adequate for analysis. It also does not report results for the listed secondary outcomes. The safety figures are based on a one-patient group and do not support broad frequency estimates or causal attribution.
The recorded dates and status indicate that the trial was terminated, but the reason for termination is not reported in the registry record. Taken together, low enrollment, absent primary measurement, lack of a control group, and limited reporting constrain the interpretation to the study's intended design and the recorded safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Window of Opportunity Trial: Avelumab in Non-metastatic Muscle Invasive Bladder Cancer — NCT03498196.
- Registry record last updated 2020-08-24; status last verified 2020-08.
- Results first posted 2020-08-24.
- 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
The registry record describes a phase 1 and phase 2, single-group, non-masked study of avelumab in patients with non-metastatic, muscle invasive bladder cancer who were eligible for radical cystectomy but ineligible for cisplatin-based neoadjuvant therapy. The planned intervention was avelumab 10 mg/kg intravenously, over 60 minutes every 2 weeks for 3 cycles or 42 days.
The study began on 2018-12-14 and had a primary completion date of 2019-12-09. It is recorded as terminated, with enrollment of 1 and a stated target of 10 evaluable patients. The primary outcome was change in tumor T-cell subpopulations between pre-study tissue and tissue collected after operation. The registry states that no assay was done. Secondary outcomes were listed, but their results are not reported in the registry record.
The safety summary records serious adverse events, other adverse events, and a death for the one-patient group. The record does not report a comparator, a statistical analysis plan, a sample-size justification, or the reason for termination.