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 Phase 1 Trial of Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer (NCT02555397), a na phase 1 study. The primary outcome is Dose-dependent Toxicity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02555397 |
| Phase | Phase 1 |
| Condition | Prostate Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Henry Ford Health System |
| Results posted | Yes |
2. Clinical Question
The study asks whether toxicity varies with dose of an oncolytic adenovirus-mediated gene therapy in men with locally recurrent prostate cancer after definitive radiotherapy, and what dose may be tolerated. Its stated primary purpose is to determine dose-dependent toxicity and the maximum tolerated dose. The primary outcome records participants with adverse events, with the stated observation period running 30 days from the adenovirus injection, defined as day 1.
Population
Men with locally recurrent prostate cancer after definitive radiotherapy. The registry record reports an enrollment of 15.
Intervention
A single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 adenovirus. Listed dose groups range from 1 x 10e10 to 1 x 10e12 viral particles.
Comparator
There is no separate control group. The registry record describes a single-group study and cautions that the dose groups are not a like-for-like control comparison.
Primary question
What dose-dependent toxicity is recorded within the stated 30-day period, and what does that information indicate about the maximum tolerated dose?
The record also names PSA response, freedom from biochemical or clinical failure, PSA doubling time, disease-specific and overall survival, and quality of life as secondary outcomes. Their results are not reported in the registry record, so the available posted results address safety counts rather than those broader clinical questions.
3. Trial Design
This is a completed phase 1, single-group study sponsored by Henry Ford Health System. The registry record lists an enrollment of 15, a start date of 2015-08, and a primary completion date of 2019-06-16. Allocation is listed as not applicable, masking as none, and the study model as single group. The record explicitly cautions that the dose groups are not a randomized comparison and should not be treated as like-for-like controls.
The intervention is Ad5-yCD/mutTKSR39rep-hIL12, described as an oncolytic adenovirus-mediated cytotoxic and interleukin 12 gene therapy. The arm description specifies a single intraprostatic injection at a dose ranging from 1 x 10e10 to 1 x 10e12 viral particles. The adverse-event results are separated into dose groups labelled 1X10e10 vp, 3x10e10 vp, 1x10e11 vp, 3x10e11 vp, and 1x10e12 vp. Each dose group has 3 participants listed as at risk for the adverse-event measures.
Because the study has no control group, differences among dose groups cannot be interpreted as if participants had been randomly assigned to comparable treatment and control conditions. The registry record does not report the allocation process among dose groups, a dose-escalation protocol, or other operational details of how doses were assigned. Those details should not be inferred from the ordered dose labels.
The primary outcome is dose-dependent toxicity, recorded as the number of participants with adverse events during 30 days from the injection, defined as day 1. The registry record lists seven outcome measures, but records no analyses. It names several secondary outcomes, while their numerical results are not 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 | AdV Dose: 1X10e10 vp | AdV Dose: 3x10e10 vp | AdV Dose: 1x10e11 vp | AdV Dose: 3x10e11 vp | AdV Dose: 1x10e12 vp |
|---|---|---|---|---|---|
| STARTED | 3 | 3 | 3 | 3 | 3 |
| COMPLETED | 2 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | AdV Dose: 1X10e10 vp | AdV Dose: 3x10e10 vp | AdV Dose: 1x10e11 vp | AdV Dose: 3x10e11 vp | AdV Dose: 1x10e12 vp |
|---|---|---|---|---|---|
| Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Arm specific adverse events
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 | AdV Dose: 1X10e10 vp | AdV Dose: 3x10e10 vp | AdV Dose: 1x10e11 vp | AdV Dose: 3x10e11 vp | AdV Dose: 1x10e12 vp | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 3 | 3 | 3 | 15 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 3 | 3 | 3 | 3 | 3 | 15 |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 3 | 3 | 3 | 3 | 3 | 15 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 2 | 2 | 3 | 2 | 9 |
| Race (NIH/OMB): White | Participants | 3 | 1 | 0 | 0 | 1 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Tumor Stage: T1c | Participants | 3 | 2 | 2 | 1 | 3 | 11 |
| Tumor Stage: T2 | Participants | 0 | 1 | 1 | 1 | 0 | 3 |
| Tumor Stage: Not Detected | Participants | 0 | 0 | 0 | 1 | 0 | 1 |
| Gleason Score: 6 | participants | 0 | 0 | 0 | 0 | 1 | 1 |
| Gleason Score: 7 | participants | 0 | 2 | 1 | 0 | 1 | 4 |
| Gleason Score: 8 | participants | 2 | 0 | 2 | 0 | 0 | 4 |
| Gleason Score: 9 | participants | 0 | 1 | 0 | 2 | 0 | 3 |
| Gleason Score: 10 | participants | 1 | 0 | 0 | 0 | 0 | 1 |
| Gleason Score: Not assessed | participants | 0 | 0 | 0 | 1 | 1 | 2 |
| Pre-T PSA (ng/ml): <4 ng/mL | Participants | 2 | 2 | 1 | 1 | 0 | 6 |
| Pre-T PSA (ng/ml): >=4 and <10 ng/mL | Participants | 0 | 0 | 1 | 1 | 2 | 4 |
| Pre-T PSA (ng/ml): >=10 ng/mL | Participants | 1 | 1 | 1 | 1 | 1 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Dose-dependent Toxicity, measured over 30 days from date of adenovirus injection (defined as day 1).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is dose-dependent toxicity, expressed as the number of participants with an adverse event in each dose group. The registry record defines the observation window as 30 days from the date of adenovirus injection, with the injection date designated day 1. This short-term safety focus fits the stated phase 1 purpose: characterizing toxicity across dose groups and informing assessment of the maximum tolerated dose.
Counting affected participants gives a direct description of how many people in each group had an event, but it does not by itself describe the event type, timing, duration, intensity, or clinical consequences. The record separates serious adverse events from other adverse events in its posted results. It does not report the adverse-event grading system, criteria for attributing an event to treatment, or a definition of dose-limiting toxicity. Those details are not reported in the registry record.
The endpoint is not an efficacy measure. Although the registry record lists PSA response, biochemical or clinical failure, PSA doubling time, survival, and quality of life as secondary outcomes, their results are not reported in the registry record. Therefore, the available endpoint data support a limited description of recorded short-term adverse events, not a conclusion about tumor response or longer-term outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted adverse-event results show no serious adverse events recorded in any listed dose group during the reported observation period: each group has 0 serious events among 3 participants at risk. The death count is also 0 in each group. These are counts within the registry record; they are not estimates demonstrating that serious harms cannot occur.
For other adverse events, the affected-participant counts are 3 among 3 at risk at 1X10e10 vp, 2 among 3 at risk at 3x10e10 vp, 2 among 3 at risk at 1x10e11 vp, 3 among 3 at risk at 3x10e11 vp, and 3 among 3 at risk at 1x10e12 vp. These counts do not form a steadily increasing pattern across the listed doses. With so few participants listed in each group, the counts are descriptive and do not establish a dose-response relationship. The registry record does not provide event-level details that would explain which kinds of events account for these counts.
The groups are not randomized controls. Differences in their counts could reflect chance, differences between the people in the groups, dose, or other factors; the posted results do not separate these possibilities. A direct causal comparison between dose groups is therefore not justified by the design information in the registry record.
No statistical analyses are recorded, and the registry record does not report confidence intervals, p-values, adjusted estimates, or a formal dose-response analysis. A confidence interval, in general, conveys the precision and range of values compatible with an estimate under a specified statistical method. Without reported intervals or model-based results, readers cannot assess precision beyond the small denominators and raw counts.
The study's stated purpose includes determining a maximum tolerated dose, but the posted results do not report a selected maximum tolerated dose or the decision rule used to select one. Nor are the secondary outcome results reported. The supported interpretation is therefore limited to the recorded adverse-event counts, not a definitive threshold for tolerability or an assessment of benefit.
9. Statistical Methods Explained
The registry record describes a single-group phase 1 study with results organized by adenovirus dose. The absence of a separate control group matters for interpretation: the dose groups are not randomized comparison arms, and the registry record expressly cautions against treating them as like-for-like controls. A difference in observed counts between dose groups is a descriptive difference, not by itself evidence that dose caused the difference.
What does a participant count describe?
The primary measure is a count of participants with an adverse event, rather than a rate per unit of follow-up or a model-adjusted effect. The listed risk denominator is 3 for each dose group. A count answers how many participants were recorded as affected within the group, but it does not indicate how many separate events occurred, whether one participant had multiple events, or how severe or long-lasting an event was. Those details are not reported in the registry record.
The record reports serious adverse events and other adverse events separately. These categories should be kept distinct when reading the results. The serious-event counts are 0 in each group; the other-event counts vary across the dose labels. The registry record does not give event terms or the criteria used to classify seriousness, so readers cannot use these totals to characterize particular symptoms or event types.
Why does the study design limit comparisons?
In a randomized controlled comparison, random allocation is intended to make groups comparable in expectation, allowing an estimate of the treatment contrast under the study design. Here, allocation is listed as not applicable, masking is listed as none, and the model is single group. There is no control arm against which to estimate an intervention effect. The available dose-specific counts can describe what was recorded in these groups, but the design information does not support a controlled causal contrast.
Even comparisons across dose groups require caution. Small group counts make the observed values sensitive to the experience of individual participants. In general, sparse binary data can produce unstable estimates and wide uncertainty; over-dispersion can also matter when participants' outcomes vary more than a simple binomial model assumes. The registry record does not report a model, an uncertainty estimate, or an analysis accounting for such variation. These are general statistical considerations, not additional analyses of this trial.
What uncertainty measures are available?
The registry record contains no analyses, and no confidence intervals or hypothesis-test results are reported. A confidence interval is a general way of expressing statistical uncertainty around an estimate, conditional on the method and assumptions used. A p-value, in general, assesses how compatible data are with a specified null model; it does not measure clinical importance or prove that a null hypothesis is true or false. Neither kind of inferential result is available in the registry record, so no such conclusion should be attributed to the posted counts.
The sample-size material associated with the results is a planning illustration, not a description of this study's observed power or its original design justification. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. That hypothetical two-arm setup differs from this single-group study organized by dose. The registry record does not report the trial's sample-size justification, a prospective power calculation, or an original statistical plan. Sample-size illustrations should therefore be read as planning scenarios rather than evidence about the trial's ability to detect an effect.
How should dose patterns be read?
A dose-response assessment would ordinarily require a prespecified definition of the outcome, an appropriate comparison or model, and a clear account of uncertainty and dose-selection rules. The registry record states that the study sought to determine dose-dependent toxicity and maximum tolerated dose, but it does not report a dose-response analysis, the dose-escalation procedure, or a maximum-tolerated-dose decision rule. The observed counts do not increase consistently across the listed dose groups. That pattern alone cannot establish the presence or absence of a dose relationship.
For outcomes measured over time, methods may need to account for follow-up duration and censoring. The registry record names survival and failure outcomes but does not report their results or analyses. No time-to-event conclusions can be drawn from the adverse-event counts. Statistical method descriptions in this explanation are general; the specific analysis methods used by the study are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists seven outcome measures, including the primary toxicity measure and secondary outcomes for PSA response, freedom from biochemical or clinical failure, PSA doubling time, disease-specific and overall survival, and quality of life. It records no analyses. The registry record does not report a statistical plan for prioritizing secondary outcomes, controlling multiplicity, or interpreting repeated tests. When several outcomes or comparisons are examined, the chance of a false-positive finding can increase unless the analysis plan addresses that issue. This is a general statistical concern; no multiplicity adjustment can be attributed to this study from the registry record.
Missing-data handling is not reported in the registry record. The posted adverse-event measures list 3 participants at risk in each dose group, but the record does not explain whether any participants had incomplete follow-up, how missing observations would be handled, or whether the listed risk group represents everyone treated at that dose. The counts should be read as recorded, not as evidence that no observations were missing.
The analysis populations are also not reported in the registry record. It does not say whether the adverse-event summaries include all enrolled participants, all participants who received an injection, or another defined population. The registry record reports an enrollment of 15, but that does not establish the population used for each outcome analysis.
These omissions limit reproducibility and the assessment of potential bias. Without definitions of the analysis populations, missing-data procedures, multiplicity strategy, and analysis plan, readers cannot determine how those choices might affect estimates or uncertainty. No additional assumptions about these methods should be made from the counts alone.
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 |
|---|---|---|---|
| AdV Dose: 1X10e10 vp | 0 | 3 | 0.0% |
| AdV Dose: 3x10e10 vp | 0 | 3 | 0.0% |
| AdV Dose: 1x10e11 vp | 0 | 3 | 0.0% |
| AdV Dose: 3x10e11 vp | 0 | 3 | 0.0% |
| AdV Dose: 1x10e12 vp | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| AdV Dose: 1X10e10 vp | 0 of 3 |
| AdV Dose: 3x10e10 vp | 0 of 3 |
| AdV Dose: 1x10e11 vp | 0 of 3 |
| AdV Dose: 3x10e11 vp | 0 of 3 |
| AdV Dose: 1x10e12 vp | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AdV Dose: 1X10e10 vp | 3 of 3 |
| AdV Dose: 3x10e10 vp | 2 of 3 |
| AdV Dose: 1x10e11 vp | 2 of 3 |
| AdV Dose: 3x10e11 vp | 3 of 3 |
| AdV Dose: 1x10e12 vp | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AdV Dose: 1X10e10 vp | AdV Dose: 3x10e10 vp | AdV Dose: 1x10e11 vp | AdV Dose: 3x10e11 vp | AdV Dose: 1x10e12 vp |
|---|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | 3 of 3 | 1 of 3 | 2 of 3 | 2 of 3 | 3 of 3 |
| Leukopenia | Blood and lymphatic system disorders | 0 of 3 | 2 of 3 | 2 of 3 | 1 of 3 | 3 of 3 |
| CPK increased | Blood and lymphatic system disorders | 1 of 3 | 1 of 3 | 2 of 3 | 3 of 3 | 1 of 3 |
| Fatigue | General disorders | 2 of 3 | 1 of 3 | 0 of 3 | 1 of 3 | 3 of 3 |
| Chills | General disorders | 0 of 3 | 2 of 3 | 0 of 3 | 2 of 3 | 3 of 3 |
| Fever | General disorders | 0 of 3 | 0 of 3 | 0 of 3 | 2 of 3 | 3 of 3 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 3 | 0 of 3 | 1 of 3 | 2 of 3 | 2 of 3 |
| ALT/SGPT increased | Blood and lymphatic system disorders | 1 of 3 | 1 of 3 | 1 of 3 | 1 of 3 | 1 of 3 |
| Hyponatremia | Blood and lymphatic system disorders | 1 of 3 | 0 of 3 | 1 of 3 | 1 of 3 | 2 of 3 |
| Diarrhea | General disorders | 0 of 3 | 1 of 3 | 0 of 3 | 0 of 3 | 3 of 3 |
The serious adverse-event counts are 0 among 3 participants at risk in each listed dose group: 1X10e10 vp, 3x10e10 vp, 1x10e11 vp, 3x10e11 vp, and 1x10e12 vp. Deaths are listed as 0 for each group. For other adverse events, the affected counts are 3, 2, 2, 3, and 3, respectively, with 3 participants at risk in each group.
These figures are participant counts, not counts of every event occurrence. They do not identify the event types, severity grades, timing, duration, or whether the events were considered related to the intervention. Such definitions and details are not reported in the registry record. The zero serious-event counts indicate only that none were recorded in these listed groups during the reported assessment; they do not demonstrate that serious events are impossible or rule out uncommon harms. The small group counts also mean the posted figures provide limited precision about the underlying frequency of adverse events.
12. What the Result Does, and Does Not, Mean
The posted data document short-term adverse-event counts by dose group in a completed phase 1 study of a gene-therapy intervention for locally recurrent prostate cancer after definitive radiotherapy. Within the 30-day observation window specified for the primary outcome, no serious adverse events or deaths are listed in the dose groups. Other adverse events are recorded for some or all participants in each group, with counts that do not rise consistently across the listed doses.
These observations do not establish that the intervention is safe, that a particular dose is safe, or that a maximum tolerated dose was identified. The registry record does not report the dose-selection rule, a formal dose-response analysis, or a selected maximum tolerated dose. Small groups and the lack of a randomized control group limit what can be inferred from differences in counts.
The results also do not answer whether the intervention affects PSA response, failure, PSA doubling time, survival, or quality of life. These are listed secondary outcomes, but their results are not reported in the registry record. No conclusions about clinical benefit can be drawn from the adverse-event counts.
In general, clinical interpretation depends on more than whether an event was recorded: event type, severity, duration, attribution, follow-up completeness, and uncertainty all matter. Those details are not available in the registry record. The appropriate reading is therefore narrow: these are the posted participant-level safety counts, with substantial limits on interpretation and no reported efficacy analysis.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the limits and role of early-phase safety data. Its stated purpose is dose-dependent toxicity assessment and determination of a maximum tolerated dose, rather than a randomized comparison of clinical effectiveness. Reporting adverse-event counts by dose makes the safety observations visible, while the single-group design and small groups require careful restraint in comparing those counts.
The distinction between a study question and the evidence posted for it is important. The study sought to characterize toxicity across dose levels, but the registry record does not report a dose-response model, a dose-selection rule, or a maximum tolerated dose. It also lists secondary clinical outcomes without reporting their results. Statistical interpretation should stay with the data actually recorded rather than treating the stated purpose as an achieved conclusion.
The record also illustrates why outcome definitions and analysis details matter. Counts of participants with events are straightforward to communicate, but without event terms, grading criteria, analysis populations, missing-data handling, or uncertainty estimates, they give only a partial account of safety. The planning illustrations associated with the results likewise need to be distinguished from the original study design: their stated assumptions concern a hypothetical two-arm planning scenario, whereas this study is single-group.
For biostatisticians and clinical researchers, the central lesson is to separate descriptive counts, inferential comparisons, and clinical decisions. Each requires a different evidential basis. In this record, the posted safety counts are useful as descriptive observations, but they do not independently establish a dose relationship, a tolerated-dose threshold, or treatment benefit.
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 safety results cover the 30-day period specified for the primary outcome; the registry record does not describe longer-term adverse-event follow-up. The small number at risk in each dose group limits precision, and a count of affected participants cannot convey event recurrence or severity. The record does not report event names, grading criteria, attribution rules, or a definition of dose-limiting toxicity.
The study has no randomized control group, and the registry record explicitly cautions against treating the dose groups as like-for-like controls. It does not report how participants were assigned to dose groups or the procedures for dose escalation. Consequently, observed differences in event counts cannot isolate a causal dose effect. The record does not report a dose-response analysis or the rule used to select a maximum tolerated dose.
Other limitations concern completeness and analysis. Missing-data procedures and analysis populations are not reported in the registry record. No confidence intervals, statistical tests, or adjusted estimates are recorded. The record lists secondary outcomes, but their results are not reported. Without those results, the safety counts cannot be combined with evidence about response, failure, survival, or quality of life.
The registry record reports an enrollment of 15, but the posted risk counts are organized by dose group and do not describe the participant flow or explain whether all enrolled participants contributed to each outcome. These limits should remain explicit when interpreting the posted results; unreported design and analysis details cannot be reconstructed from the counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 1 Trial of Interleukin 12 Gene Therapy for Locally Recurrent Prostate Cancer — NCT02555397.
- Registry record last updated 2024-10-10; status last verified 2024-07.
- Results first posted 2024-10-10.
- 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 completed phase 1, single-group study sponsored by Henry Ford Health System, with enrollment of 15. It evaluates a single intraprostatic injection of Ad5-yCD/mutTKSR39rep-hIL12 at listed doses from 1 x 10e10 to 1 x 10e12 viral particles in men with locally recurrent prostate cancer after definitive radiotherapy. The primary outcome is dose-dependent toxicity during 30 days from injection.
The posted serious adverse-event and death counts are 0 in each listed dose group; other adverse-event counts range from 2 to 3 affected participants among 3 at risk per group. The record cautions that the dose groups are not a randomized comparison. Although secondary outcomes are listed, their results are not reported in the registry record, and no analyses are recorded. A maximum tolerated dose and the methods used to select one are not reported in the registry record.