Sorafenib to Overcome Resistance to Systemic Chemotherapy in Androgen-independent Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sorafenib to Overcome Resistance to Systemic Chemotherapy in Androgen-independent Prostate Cancer (NCT00414388), a na phase 1, phase 2 study. The primary outcome is Percentage of Patients Needing a Dose Reduction..

2. Clinical Question

The primary question concerns treatment delivery and tolerability as expressed through dose modification. A dose reduction is a change in the amount of drug administered; the registry defines the endpoint as the number of patients requiring a reduction divided by the total number of patients, expressed as a percentage. It does not state the reasons for individual reductions or report how reductions were distributed over follow-up.

The brief study objective focuses on safety when sorafenib is combined with chemotherapy, naming mitoxantrone or docetaxel. However, the listed intervention and arm description specify single-agent sorafenib. The registry record does not explain this difference or provide further treatment-regimen details. The outcomes also include overall clinical benefit, described as the sum of complete response, partial response, and stable disease, and a PSA biochemical response. Their numerical results are not reported in the record.

3. Trial Design

This is a completed Phase I/II study with a single-group model. The registry lists enrollment of 22 participants, no masking, and allocation as NA. There is no listed control arm, so the study design does not provide a concurrent randomized comparison. The registry names Oncology Specialists, S.C. as sponsor, records the start as 2006-12, and gives 2011-09 as the primary completion date.

The study title and official title describe an investigation of sorafenib in overcoming resistance to systemic chemotherapy in androgen-independent prostate cancer. The brief objective is to evaluate the safety of combining sorafenib and chemotherapy, specifically mitoxantrone or docetaxel. In contrast, the intervention listing names sorafenib, and the arm description is “Oral Single agent Sorafenib 400mg twice daily.” The registry record does not clarify whether the listed arm description covers all treatment received or how the chemotherapy named in the objective relates to the arm.

The primary outcome is the percentage of patients needing a dose reduction. The outcome description says that the percentage is based on the number of patients requiring a reduction divided by the total number of patients. The record reports 15 patients requiring dose reductions and states that participants were followed for an average of 25 months. It does not report individual follow-up durations, the timing or reasons for reductions, or how the endpoint was handled for participants whose follow-up differed.

The registry also identifies overall clinical benefit and PSA biochemical response as secondary outcomes. Detailed definitions, assessment schedules, and numerical results for these outcomes are not reported in the registry record. The record lists no analyses, and it does not describe a prespecified statistical analysis plan or sample-size justification. The single-group design is important when interpreting any observed event frequency: it describes outcomes in this study group, without a randomized control group to distinguish treatment-related effects from other explanations.

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: Eligible patients were those who progressed while receiving chemotherapy (docetaxel or mitoxantrone)or within 12 weeks of stopping chemo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 15 patients required dose reductions.

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: Recruitment was from our clinic population. Eligible patients were those who progressed while receiving chemotherapy (docetaxel or mitoxantrone)or within 12 weeks of stopping chemo

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Needing a Dose Reduction., measured over participants were followed for an average of 25 months.

The primary endpoint is the percentage of patients needing a dose reduction. The registry describes its calculation as the number of patients requiring a dose reduction divided by the total number of patients, multiplied by 100%. It reports that 15 patients required dose reductions, but the resulting percentage is not reported in the registry record. The record also gives enrollment of 22; it does not separately state the endpoint denominator used in the calculation.

Dose reduction is a treatment-delivery measure. It captures whether participants required a lower dose during the study, which can be relevant to describing tolerability and the practical demands of a regimen. It is not itself a direct measure of tumor response, survival, or the severity of an adverse event. Nor does the endpoint description say why a reduction occurred. Without reasons, timing, and a clearly stated analysis population, the count cannot distinguish reductions prompted by adverse events from reductions for other reasons.

The stated average follow-up was 25 months. The registry record does not describe how long each participant was observed or whether dose reductions were assessed over a common time window. The endpoint should therefore be read as a descriptive record of patients requiring reductions, not as a time-to-event estimate. The registry does not report a confidence interval or an inferential comparison for this outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary outcome as a percentage and describes it as the number of patients requiring dose reduction divided by the total number of patients. It reports 15 patients requiring reductions. The record does not state the resulting percentage, the denominator used for that calculation, or an analysis population distinct from enrollment. These omissions matter because a percentage depends on both its numerator and denominator. Enrollment alone should not automatically be treated as the number analyzed when the record does not explicitly make that link.

What does a descriptive percentage tell the reader?

General explanation: a proportion summarizes how often an event was observed within a defined group. Its interpretation depends on how the event is defined, who was eligible to be counted, and whether participants had comparable opportunities for the event to occur. For a dose-reduction endpoint, readers also need to know which reductions qualify, whether repeated reductions count once per patient or in another way, and what observation period applies. The registry provides a patient-based description and an average follow-up of 25 months, but it does not report further operational details.

General explanation: a confidence interval describes statistical uncertainty around an estimate under specified assumptions. It is not a guarantee that the underlying value lies within a particular range, and its width depends on information such as the number analyzed and the event frequency. No confidence interval for the primary endpoint is reported in the registry record. Without an interval or another uncertainty measure, the precision of the reported result cannot be evaluated from the record.

Why does the study design affect interpretation?

The study is listed as single-group, with allocation NA and masking none. General explanation: a single-group study can describe what happened among participants who received the study regimen, but it does not create a contemporaneous control group. A comparison against another regimen would need suitable comparative data; none is listed. Observed outcomes may reflect the regimen, participant characteristics, clinical decisions, follow-up, or other factors. The design does not allow those possibilities to be separated through a randomized contrast.

The study is identified as Phase I/II. The registry's brief objective emphasizes safety for sorafenib combined with chemotherapy, naming mitoxantrone or docetaxel. Yet the listed intervention is sorafenib and the arm description specifies oral single-agent sorafenib at 400mg twice daily. The registry does not explain the relationship between these descriptions. This affects the clarity of the population-treatment context, rather than changing the arithmetic definition of the dose-reduction endpoint.

What can be inferred from the adverse-event summaries?

The serious-adverse-event summary gives 22 at risk and 12 affected for the listed group. It also supplies percentages for selected serious-event terms. General explanation: an event proportion is most interpretable when the record defines whether it counts participants or event episodes, provides the observation window, and explains coding and attribution. Those details are not reported for the listed terms. The summary therefore describes the registry's reported counts and percentages, but does not on its own establish causality or provide a complete account of event burden.

The record separately reports other adverse events for 22 at risk and 22 affected. It does not give a more detailed definition of this category in the registry record. The deaths entry is null, which means the record does not report a deaths value; it should not be read as a reported zero. General explanation: missing entries and explicit zero counts are different data states and should not be conflated.

What do the planning assumptions mean?

General explanation: a sample-size calculation is a planning exercise that estimates how much information a future study might need under stated assumptions. It is not a measure of the power achieved by an already completed study. The registry record does not report its own sample-size justification. The stated planning assumptions describe an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the stated illustration concerns a total number of events, while other illustrations are expressed as participants per arm. Such assumptions do not turn this single-group study into a randomized comparison, nor do they establish that the study used those planning methods.

The record lists no analyses. It therefore does not report an inferential model, adjustment variables, a method for handling repeated measurements, or a statistical procedure for the primary or secondary outcomes. General explanation: a statistical analysis plan specifies how endpoints, populations, missing observations, and comparisons will be treated. These choices can affect estimates and their interpretation. Where they are not reported, readers should avoid assuming that a particular method was used.

Overall, the available statistical information supports a descriptive reading of the reported counts and event summaries. It does not permit a reconstruction of unreported percentages, an assessment of interval-based precision, or verification of a formal comparative analysis.

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("Single Agent Sorafenib")
n      <- c(21)
events <- c(15)
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  Single Agent Sorafenib  21  15  71.4  47.8  88.7  50.0  86.2  49.8  86.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the dose-reduction percentage as the primary outcome and lists overall clinical benefit and PSA biochemical response as secondary outcomes. Overall clinical benefit is described as the sum of complete response, partial response, and stable disease. Numerical results for those secondary outcomes are not reported in the registry record. The record does not describe a hierarchy among secondary outcomes, prespecified hypotheses, or a method for accounting for multiple outcome assessments.

General explanation: when a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of a misleading positive finding can increase if each is interpreted independently. A prespecified outcome hierarchy or multiplicity adjustment can help define how findings are interpreted. The registry record does not state whether such procedures were planned or used. Because no analyses are listed, there are no reported tests or adjusted results to assess.

The record reports 15 patients requiring dose reductions and enrollment of 22, but does not state an explicit analysis population or the denominator used to calculate the percentage. It gives an average follow-up of 25 months without reporting individual follow-up or the handling of participants with incomplete observations. Missing-data methods, exclusions, and analysis-population definitions are not reported in the registry record.

These omissions do not demonstrate that data were missing, that participants were excluded, or that multiplicity procedures were absent in practice. They mean those details cannot be established from the registry record. General explanation: transparent reporting of who was analyzed, how missing outcomes were handled, and which comparisons were planned helps readers judge whether a result applies to the enrolled group and how much flexibility existed in selecting analyses.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary retention (9.1%), constipation (9.1%), adominal pain (9.1%), pneumonia (9.1%), anemia (4.5%).

The registry lists 22 participants at risk for serious adverse events and 12 affected in the single-agent sorafenib group. It lists 22 participants at risk and 22 affected for other adverse events. These are reported group summaries; the record does not describe the event-level counting rules or whether the categories overlap.

The top serious-event terms are urinary retention, constipation, Adominal Pain, and pneumonia, each reported as 9.1%. Anemia and hypoglycemia are each reported as 4.5%. “Adominal Pain” is the spelling used in the registry record. The record does not clarify the denominator or calculation basis for each listed term, and the percentages should be read as reported rather than used to infer additional counts.

These summaries do not establish that sorafenib caused the events. The registry record does not report attribution, event timing, duration, recurrence, or severity grading for the listed terms. The deaths field is not populated, so deaths are not reported in the registry record; this is not equivalent to a reported absence of deaths. The listed safety data describe the entries in the record, not a comparative safety estimate.

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

The results describe dose reductions and adverse-event summaries in a completed, single-group Phase I/II study. The registry reports 15 patients requiring dose reductions, but not the calculated percentage or its denominator. It also reports serious adverse events in 12 of 22 at risk and other adverse events in 22 of 22 at risk. These figures can be read as descriptive observations for the listed group, subject to the limits of the record's definitions and reporting.

The primary endpoint concerns the need for dose modification, not tumor response or survival. The registry lists overall clinical benefit and PSA biochemical response as secondary outcomes, but their numerical results are not reported in the registry record. The dose-reduction count alone therefore cannot answer those secondary questions. Nor does the record provide reasons for reductions, so it cannot show whether they followed adverse events or other circumstances.

The study has no listed comparator arm. Accordingly, the reported observations do not establish how the outcomes compare with another treatment or with a different treatment strategy. They also do not establish that the regimen caused the events recorded. The mismatch between the stated objective of combining sorafenib with chemotherapy and the arm description of single-agent sorafenib adds uncertainty about the treatment context represented by the listed results.

Statistical precision is also unclear. No confidence interval, hypothesis test, or analysis is listed, and the percentage endpoint is not reported. The stated average follow-up does not show how observation time varied among participants. These limits mean that the record supports a narrow descriptive account, rather than a precise comparative conclusion.

General explanation: a result's meaning depends on its endpoint, study design, completeness of reporting, and uncertainty. A numerical count can be informative about what the registry records, while still being insufficient to establish causation, comparative effects, or generalizability. The record does not report enough detail to resolve those broader questions.

14. Why This Trial Matters Statistically

This study raises several statistical interpretation issues that are common in clinical research. The primary outcome is a percentage, but the registry gives the count of patients requiring a dose reduction without reporting the resulting percentage or explicitly stating its analysis denominator. A percentage is not fully interpretable unless the counted event and the population in its denominator are clear. This distinction is especially important when a record lists enrollment separately from an outcome count.

The single-group design is another central feature. It allows a descriptive account of outcomes among participants in the study but does not provide a randomized control comparison. Readers should distinguish a frequency observed in a group from an estimate of a difference between treatment strategies. Those are different statistical questions and require different designs and data.

The record also illustrates why consistency in describing the intervention matters. The objective refers to sorafenib combined with chemotherapy, while the listed arm describes single-agent sorafenib. Without clarification, the clinical context for the outcome is less certain. Statistical interpretation depends not only on calculations but also on knowing which treatment and population those calculations describe.

Finally, reported event counts and percentages need context. The serious-adverse-event summary supplies affected and at-risk counts and selected term percentages, but lacks details on event definitions, attribution, timing, and the deaths entry. The registry lists secondary outcomes but not their numerical results, and it lists no analyses. These gaps do not prove that analyses or additional data did not exist; they limit what can be verified from the registry record. The case underscores the value of clearly reporting denominators, analysis populations, outcome definitions, uncertainty, and the relationship between study objectives and treatment arms.

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 single-group design is a major trial-specific limitation for comparative interpretation. No control arm is listed, so the registry results cannot establish a between-group difference. The record also gives allocation as NA and masking as none. These design features should be kept in view when interpreting the dose-reduction and adverse-event summaries.

The treatment description is not fully consistent across the record. The brief objective concerns combining sorafenib with chemotherapy and names mitoxantrone or docetaxel, while the listed arm describes oral single-agent sorafenib at 400mg twice daily. The registry record does not explain the discrepancy, specify chemotherapy administration in the arm, or clarify which treatment context applies to the reported outcomes.

For the primary endpoint, the registry reports 15 patients requiring dose reductions but not the resulting percentage or the explicit analysis denominator. It does not provide reasons, timing, or details on repeated reductions. Although average follow-up is stated as 25 months, individual observation times and the endpoint assessment window are not reported. The record therefore does not support a detailed account of when or why dose modifications occurred.

The adverse-event summary lacks reported definitions and event-level details for the listed terms. Attribution, timing, duration, severity grading, and the basis of the term percentages are not reported in the registry record. The deaths field is unpopulated. Secondary-outcome results, an analysis plan, confidence intervals, missing-data methods, and analysis-population definitions are also not reported. These omissions restrict assessment of precision and completeness; they should not be treated as evidence that an event, analysis, or procedure was absent in practice.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sorafenib to Overcome Resistance to Systemic Chemotherapy in Androgen-independent Prostate Cancer — NCT00414388.
• Registry record last updated 2014-04-07; status last verified 2014-02.
• Results first posted 2014-04-07.
• 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

The registry describes NCT00414388 as a completed Phase I/II study in androgen-independent prostate cancer, sponsored by Oncology Specialists, S.C. It records enrollment of 22 participants, a single-group design, no masking, and allocation as NA. The listed arm describes oral single-agent sorafenib at 400mg twice daily, while the study objective describes evaluating sorafenib combined with chemotherapy.

The primary outcome is the percentage of patients needing a dose reduction. The registry reports 15 patients requiring reductions and an average follow-up of 25 months, but does not report the resulting percentage. Serious adverse events are listed for 12 of 22 at risk; other adverse events are listed for 22 of 22 at risk. Secondary outcomes are named, but numerical results and statistical analyses are not reported in the registry record.