Docetaxel, Androgen Ablation, and External-Beam Radiation Therapy in Patients With High-Risk Localized Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Docetaxel, Androgen Ablation, and External-Beam Radiation Therapy in Patients With High-Risk Localized Prostate Cancer (NCT00225420), a na phase 1, phase 2 study. The primary outcome is Number of Patients Experiencing Dose-Limiting Toxicities.

2. Clinical Question

This phase I/II study was intended to examine side effects and the best docetaxel dose when the drug was given with androgen ablation and external-beam radiation, as well as to assess how the treatment program performed in this population. Those aims do not make the study a comparative effectiveness trial: without a control group, differences from an alternative treatment cannot be estimated from this design. The record also lists biochemical progression-free survival as a secondary outcome, but does not report its results.

3. Trial Design

The registry identifies NCT00225420 as a completed phase I/II study sponsored by UNC Lineberger Comprehensive Cancer Center. It lists a start date of 2005-08, a primary completion date of 2010-06, and enrollment of 23 participants. The condition is prostate cancer. The title and study description specify high-risk localized prostate cancer.

The design is recorded as single-group, with allocation not applicable and no masking. All participants were assigned to the single arm described in the record; there is no randomized or concurrent control arm. Accordingly, the study can describe outcomes observed in its participants, but its design does not isolate the effect of the treatment program relative to another approach.

The intervention list names docetaxel, leuprolide acetate, and radiation therapy. The arm description says participants initially received leuprolide acetate and began adaptive external-beam radiation 2-3 months after hormonal therapy started. The available description ends before the full regimen is specified. Further scheduling, dose-level details, and treatment delivery information are not reported in the registry record.

The primary endpoint is the number of participants with dose-limiting toxicities, assessed at each dose level. The stated follow-up timeframe is an average of 2 years. The record lists two outcome measures and identifies biochemical progression-free survival as a secondary outcome. It lists zero analyses, and does not report the primary endpoint results, the secondary outcome results, or a statistical analysis plan. A protocol-level sample-size justification is 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.

Before assignment: Two patients were taken off the study due illness, two were removed because they were too large for the equipment, and one was removed due to CT screen failure.18 men with high-risk or locally advanced prostate cancer were enrolled. All 18 patients completed their radiation therapy and 16 completed all planned chemotherapy doses.

Overall 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: All patients included in this trial were high-risk localized (Gleason 8-10 or PSA level \>= 20 ng/mL) prostate cancer, or T3 disease.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Experiencing Dose-Limiting Toxicities, measured over Average follow up of 2 years.

The primary endpoint is a count: the number of participants experiencing a dose-limiting toxicity at each dose level. The record defines DLT as grade 3-4 non-haematological toxicity or grade 4 haematological toxicity, assessed using Common Terminology Criteria for Adverse Events version 3.0. The stated timeframe is an average follow up of 2 years.

A toxicity count is useful in a dose-finding study because it describes how often a prespecified level of toxicity occurred among participants receiving a dose. It can inform consideration of tolerability alongside other clinical and protocol considerations. The endpoint is not a direct measure of tumor response or disease control, and it does not by itself establish the comparative safety of a treatment program. Here, the record says the count was to be determined at each dose level, but does not report the number of participants treated at each dose or the DLT count for any dose. Therefore, the endpoint’s observed frequency and its precision cannot be assessed from the registry results listed in this record.

The record also lists biochemical progression-free survival as a secondary outcome. Its definition, event results, and analysis details are not reported in the registry record. No conclusions about that outcome can be drawn from its listing alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a phase I/II, single-group study. The statistical implications of that structure matter when reading the endpoint. Phase I/II identifies the study phase, but the label alone does not specify the dose-escalation method, rules for selecting a dose, or analysis plan. Those details are not reported in the registry record. It is therefore not possible to infer how dose levels were assigned or how a dose was chosen.

What does a count endpoint represent?

A count endpoint records the number of participants who meet a defined event criterion. For this study, the event is a DLT under the stated toxicity criteria. To interpret a count as a frequency, the count must be considered with its denominator: the number of participants who received the relevant dose and were assessed for the endpoint. A count without that denominator does not reveal how common the event was among exposed participants. The registry record does not report the dose-specific counts or denominators.

When a count is converted to a proportion, uncertainty depends on the number of participants and the number who experience the event. A confidence interval is a way to express the uncertainty around an estimate under specified statistical assumptions. It is not a guarantee that the true value lies in a particular interval, nor does it address problems such as incomplete outcome ascertainment or a biased study design. No DLT estimate or confidence interval is reported in the registry record, so the endpoint's uncertainty cannot be evaluated.

Why does the single-group design matter?

In a single-group study, outcomes can be described among participants who received the study regimen. There is no concurrent control group from which to estimate what would have happened under another treatment or no study treatment. A comparison with an external benchmark would require a clearly defined and appropriate reference, along with assumptions about how comparable the groups are. No such comparison or benchmark is reported in the registry record. Thus, the design is suited to describing observed events, but cannot on its own establish a causal treatment contrast.

The absence of masking means treatment assignment and treatment receipt were not masked, as recorded. For a toxicity endpoint, judgments about symptoms, clinical assessments, and event classification can be susceptible to knowledge of treatment. The defined grading criteria help specify what qualifies as a DLT, but the record does not say whether outcome assessment was independent or whether any additional safeguards were used. These details are not reported in the registry record.

How should the planning illustrations be understood?

The planning assumptions described for the site's sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustration is framed around detecting a stated fraction of an observed effect. Such assumptions are generic planning inputs, not evidence that this single-group trial was designed with two arms or that a particular analysis was conducted. They are not the trial's own design justification, and the registry record does not report the protocol's sample-size rationale. Any sample sizes generated under such assumptions are planning illustrations, not observed trial results or a measure of achieved power.

The normal approximation is a simplifying approach to estimating sampling variability. Its suitability depends on the data and design. For a binary event, sparse event counts or small denominators can make approximate methods less reliable; exact or other methods may be considered in general. The registry record does not identify which inferential method, if any, was planned for DLT, and it reports zero analyses. No particular method should therefore be attributed to the investigators.

Over-dispersion is a general issue when observed variation exceeds what a simple probability model assumes. It can arise when participants' event risks vary more than the model allows, and ignoring it may make uncertainty appear smaller than it is. This is a general statistical consideration, not a claim about the trial data. No model estimates or dispersion measures are reported in the registry record.

The registry also names biochemical progression-free survival as a secondary outcome. Time-to-event analysis generally accounts for the timing of events and for participants whose event status is not observed through the full follow-up period. Such analyses depend on definitions of the event, censoring rules, follow-up, and assumptions about missing outcomes. The record does not provide these analysis details or results, so no survival estimate or interpretation can be reconstructed.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Docetaxel at 10 mg/m2", "Docetaxel 15 mg/m2", "Docetaxel 20 mg/m2")
n      <- c(9, 6, 3)
events <- c(1, 1, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Docetaxel at 10 mg/m2  9  1  11.1  0.3  48.2  2.0  43.5  2.5  44.5
ARM  Docetaxel 15 mg/m2  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Docetaxel 20 mg/m2  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary count of participants experiencing DLT and the secondary outcome of biochemical progression-free survival. It does not report whether the study used a prespecified hierarchy, adjusted significance thresholds, or another strategy for interpreting multiple outcomes. A multiplicity plan is not reported in the registry record. Without such information, the outcome listing alone does not establish how any statistical findings were to be prioritized or interpreted.

The record lists zero analyses and does not report inferential results for either outcome. It therefore does not state which analysis populations were used, whether participants were analyzed as enrolled or according to treatment received, or how participants with incomplete outcome data were handled. The number assessed for each endpoint and the amount or pattern of missing data are not reported in the registry record.

Missingness can affect interpretation when the likelihood of having an observed outcome is related to participant characteristics or outcomes themselves. In general, a complete-case analysis describes participants with recorded outcomes and may not represent all enrolled participants if follow-up is incomplete in a systematic way. Other approaches make additional assumptions and require adequate information about missingness. The record does not identify an approach, so none can be attributed to the study.

The enrollment count is 23, while the safety summaries list 18 participants at risk in each of the serious and other adverse-event categories. The record does not explain the relation between these denominators and enrollment, nor does it describe exclusions, follow-up completeness, or endpoint-specific evaluability. The difference in the listed counts should not be interpreted as a particular reason for non-inclusion. A participant flow account and analysis-population definitions are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety record lists 18 participants at risk for serious adverse events, with 0 affected, and 18 at risk for other adverse events, with 18 affected. It also lists 0 deaths. These are counts within the categories recorded; they should be read as descriptive safety data rather than as comparative estimates, because the study has a single group and no control arm.

The record does not list serious adverse event terms, and does not explain the specific events included in the other-adverse-event category. The 18 participants with other adverse events therefore cannot be characterized further by event type or severity from the reported information. The record also does not clarify whether these safety denominators include all enrolled participants or how they relate to DLT assessment.

Serious adverse events and dose-limiting toxicities are not interchangeable endpoint labels. DLT has a specific definition in the record based on toxicity grade and type, while the safety summary uses serious and other event categories. The serious-event count of 0 does not establish that no DLTs occurred, and the other-event count does not establish how many met the DLT definition. The DLT results are not reported in the registry record.

13. What the Result Does, and Does Not, Mean

The study record documents a phase I/II evaluation of a combined treatment program in participants with high-risk localized prostate cancer. It specifies a primary safety-related question: the number of participants experiencing defined dose-limiting toxicities at each dose level. It also records enrollment of 23 participants and selected safety counts. These registry entries describe the study and the available registry data; they do not supply the missing primary endpoint results.

Because no dose-specific DLT counts or denominators are reported, the frequency of DLT cannot be determined from the record. The listed serious and other adverse-event figures do not fill that gap, because the record does not map those categories to the DLT definition. The listed secondary outcome, biochemical progression-free survival, also has no reported result. Thus, the data recorded do not permit a numerical conclusion about toxicity by dose or disease progression.

The single-group, unmasked design has further limits. It can describe outcomes in the treated group, but it cannot provide a randomized comparison with another treatment. Even if outcome results were available, observed outcomes would not by themselves establish that the treatment program caused a change in toxicity or disease course. No conclusion that the regimen works or does not work follows from the registry entries.

The safety data show 0 serious adverse events among 18 participants at risk and 18 participants with other adverse events among 18 at risk; deaths are listed as 0. These counts do not identify event types in the other category, and no serious-event terms are listed. They should not be generalized beyond the recorded categories and participants. Overall, the registry establishes what the study set out to assess and some aggregate safety information, but its missing endpoint results and analysis details preclude a fuller statistical assessment.

14. Why This Trial Matters Statistically

This study illustrates why a clear endpoint definition is necessary but not sufficient for statistical interpretation. The registry specifies which toxicity grades and types qualify as DLT and identifies the intended dose-level assessment. That definition gives a reader a framework for understanding what the primary outcome means. But without dose-specific event counts and denominators, the endpoint cannot be quantified or compared across dose levels.

It also demonstrates the distinction between a safety summary and the primary endpoint. Serious adverse events, other adverse events, and DLT are related safety concepts, but they are not interchangeable. A registry can report aggregate safety categories while omitting the details needed to evaluate a defined primary endpoint. Keeping those measures conceptually separate prevents the safety counts from being mistaken for the DLT result.

The single-group design is another important statistical feature. A study can document events among participants receiving a treatment program without providing a control-based estimate of what would have occurred under an alternative. Recognizing that distinction helps avoid causal claims that the design cannot support. The phase I/II designation signals the broad study stage, but does not reveal the dose-selection rules or analysis plan; those are not reported in the registry record.

Finally, this record highlights that enrollment alone does not establish the precision of an outcome estimate. The number assessed at each dose and the observed event count are needed to interpret a count endpoint, and analysis methods and missing-data handling are needed to understand how results were produced. When these details and the outcome results are absent, the statistically appropriate conclusion is limited: the question and definitions are recorded, but the primary answer cannot be assessed.

15. 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 most direct limitation is that the registry record does not report the primary DLT results. It gives the endpoint definition and timeframe, but no count by dose level, no corresponding dose-level denominators, and no uncertainty estimates. Therefore, the principal outcome cannot be interpreted quantitatively.

The record is single-group and unmasked, with no control arm. It cannot estimate a randomized contrast, and any descriptive outcome would not by itself establish a causal treatment effect. The available intervention description is incomplete, so the full regimen and dose details are not reported in the registry record. Dose-level assignment and selection procedures are also not reported.

Although enrollment is listed as 23, safety denominators are 18. The record does not explain how those denominators were determined or how they relate to endpoint assessment. Participant flow, the analysis populations, follow-up completeness, and missing-data handling are not reported in the registry record. This limits assessment of who contributed to each outcome and whether observed participants represent all enrolled participants.

The record lists biochemical progression-free survival as a secondary outcome but does not report its definition, result, follow-up details, or analysis. It also does not report a statistical analysis plan, multiplicity strategy, or protocol-level sample-size justification. No conclusions about outcome precision, dose selection, or comparative performance can be made from the available information. The safety categories do not provide event terms for other adverse events, and the relationship between those categories and the defined DLT endpoint is not specified.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Docetaxel, Androgen Ablation, and External-Beam Radiation Therapy in Patients With High-Risk Localized Prostate Cancer — NCT00225420.
• Registry record last updated 2017-06-01; status last verified 2017-04.
• Results first posted 2017-06-01.
• 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.

19. Record Summary

NCT00225420 is a completed phase I/II, single-group study sponsored by UNC Lineberger Comprehensive Cancer Center. The record lists 23 enrolled participants, a start date of 2005-08, and a primary completion date of 2010-06. The treatment program involved docetaxel, leuprolide acetate, and adaptive external-beam radiation therapy for high-risk localized prostate cancer.

The primary endpoint was the number of participants experiencing dose-limiting toxicities at each dose level, using the stated toxicity-grade definition and an average follow up of 2 years. The record lists biochemical progression-free survival as a secondary outcome. It does not report results for either outcome or a statistical analysis plan. Safety summaries list 0 serious adverse events among 18 participants at risk, 18 participants with other adverse events among 18 at risk, and 0 deaths. The single-group design does not provide a randomized treatment comparison.