Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (NCT03413995), a na phase 2 study. The primary outcome is Number of Participants With Prostate Specific Antigen (PSA) >=50 Response.

2. Clinical Question

The clinical question is about PSA response in a specific treatment setting: metastatic disease that remains hormone-sensitive, before androgen deprivation therapy, among men with inherited DNA-repair gene mutations. The registry describes the primary outcome as a count of participants meeting the PSA-response definition, rather than a comparison of response rates between treatment groups.

The study description also identifies safety and other outcomes, including PSA progression-free survival, progression-free survival, and objective response. However, the record does not report results for the primary PSA-response measure or those secondary outcomes. Therefore, the clinical question is identifiable, but the posted record does not establish how many participants met the response definition or how outcomes compared with any alternative treatment.

3. Trial Design

NCT03413995 is a completed phase II study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The record lists an enrollment of 12 and describes a single-group model. Allocation is recorded as NA, and masking is listed as none. No separate control arm is described, so the trial does not offer a randomized comparison between rucaparib and another treatment or a control condition.

The intervention is rucaparib, described as 600 mg by mouth twice daily with continuous dosing. The target population was men with metastatic hormone-sensitive prostate cancer and germline mutations in DNA-repair genes. The study description specifies that participants had not yet been treated with androgen deprivation therapy.

The registry lists the study start as 2018-09-10, primary completion as 2023-11-08, and overall status as completed. These dates describe the record’s trial timeline; they do not provide results or explain the timing of individual participants’ treatment or assessments.

The primary outcome is the number of participants with a PSA decline to at least 50% of baseline, confirmed by a second measurement at least 4 weeks apart. Its listed timeframe is 4 weeks. The record also names treatment-related adverse events, PSA progression-free survival, progression-free survival, and objective response as secondary outcomes. It does not report their outcome values or the detailed methods used to analyze them.

The design is suited to describing what occurred in this treated group, but without a comparator it cannot separate the effect of treatment from other explanations for observed changes. The registry record does not report a protocol-level statistical plan, a rationale for the enrollment target, or details of any interim analyses.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Prostate Specific Antigen (PSA) >=50 Response, measured over 4 weeks.

The primary endpoint counts participants who achieved a specified PSA response: a decline to at least 50% of baseline, confirmed by a second measurement at least 4 weeks apart. PSA is a blood marker used in prostate cancer assessment. A threshold-based response measure turns an individual’s change from baseline into a defined outcome that can be counted across the study group.

The requirement for confirmation means the response definition is not based solely on a single qualifying measurement. In general, confirmation can help distinguish a sustained change from a transient fluctuation or measurement variation. The registry describes the confirmation interval but does not provide further detail about measurement schedules, laboratory procedures, or how missing or unevaluable measurements were handled.

The record lists the endpoint timeframe as 4 weeks, while its description says that confirmation requires a second measurement at least 4 weeks apart. It does not explain how these two timing statements fit together. This leaves the exact assessment schedule unclear in the registry record.

The endpoint is a response count, not a time-to-event measure. It can describe how many participants met the stated PSA criterion, but on its own it does not describe how long a response lasted, whether cancer progressed, or how outcomes compare with an untreated or alternative-treatment group. The record gives the endpoint definition but does not report the number of participants who met it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group result describe?

The trial is listed as single-group, with no comparator described. A single-group analysis summarizes outcomes among people who received the study intervention. It can report how many met an endpoint, but there is no concurrent group in this record to show what would have happened under a different intervention or control condition.

General statistical explanation: a treatment comparison aims to distinguish differences associated with assigned interventions from background changes and other influences. Without a comparison group, those influences cannot be separated through a randomized contrast. This is why a response count in a single-group study is descriptive rather than a comparative estimate of treatment effect.

What does the primary endpoint count?

The primary endpoint is a participant count based on a PSA decline to at least 50% of baseline, with confirmation by a second measurement at least 4 weeks apart. It is a binary outcome at the participant level: a participant either meets the stated response definition or does not, assuming the necessary measurements are available. The registry record does not report the count meeting the definition, the number with evaluable measurements, or an estimate of the response proportion.

General statistical explanation: for a binary endpoint, a confidence interval expresses uncertainty around an estimated event frequency. Its width reflects the amount of information in the data as well as the observed frequency. No confidence interval or primary response estimate is reported in the registry record, so the precision of the endpoint cannot be judged from the posted results.

How should the timing language be read?

The endpoint timeframe is listed as 4 weeks, while the description requires a confirming measurement at least 4 weeks after the first qualifying measurement. The registry does not clarify whether the timeframe refers to the first assessment, the confirmation, or another convention. It also does not report the detailed schedule of PSA measurements. Interpretation of the endpoint timing should therefore remain limited to the wording in the record.

General statistical explanation: time-to-event endpoints account for both whether an event occurs and when it occurs. Their analysis often needs rules for censoring participants whose event time is not observed during follow-up. The registry names PSA progression-free survival and progression-free survival as secondary outcomes, but does not report definitions, follow-up summaries, censoring rules, estimates, or analyses for them.

What can the adverse-event counts tell readers?

The record lists counts of participants affected by serious and other adverse events and the number of deaths. These are descriptive safety figures for the listed group. It also names three top serious-event terms with percentages. The record does not provide treatment exposure duration, event onset or resolution, participant-level overlap between categories, or a comparison group. These omissions prevent interpretation of the counts as comparative rates.

General statistical explanation: event counts and event rates answer different questions. A rate incorporates the time participants are observed or exposed, while a simple count does not. If time at risk differs across participants, counts alone may not represent how frequently events occurred over comparable observation periods. No exposure-adjusted rate is reported in the registry record.

What do the planning assumptions mean?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The described effect to detect is a stated fraction of the observed effect. Those assumptions are not the design of this single-group trial: the record does not list a two-arm randomized comparison. The actual planning outputs are not included in the registry record for this analysis, so no participant requirement can be stated.

General statistical explanation: a planning calculation estimates how much information a future study might need under specified assumptions. It is not a measure of the probability that the current study’s result is true, and it is not observed power. Such calculations depend on the chosen effect, variability or event frequency, significance level, and design. The registry record does not report the trial’s own sample-size justification, so the planning illustration should not be treated as evidence of the original design rationale.

What is not available for statistical review?

The record reports no analysis entries and does not describe the analysis population, missing-data handling, adjustment methods, or multiplicity strategy. It also does not report a primary endpoint estimate or interval. General statistical explanation: analysis choices can affect which participants contribute to an estimate and how uncertainty is quantified. Without those details and the outcome data, readers cannot reproduce or independently assess the primary 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("Rucaparib 600 mg BID")
n      <- c(12)
events <- c(5)
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  Rucaparib 600 mg BID  12  5  41.7  15.2  72.3  19.3  68.0  19.2  68.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary PSA-response endpoint and several secondary outcomes: treatment-related adverse events, PSA progression-free survival, progression-free survival, and objective response. It also lists five outcome measures overall. The record does not state how the primary endpoint was distinguished from other measures for formal hypothesis testing, whether any secondary outcomes were intended to support confirmatory claims, or how multiple statistical tests were handled. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

The record lists no analysis entries. It does not report the analysis population for the primary endpoint, whether participants were analyzed according to a prespecified rule, or how participants without the measurements needed for confirmation were treated. Missing-data methods, exclusions, and counts of participants with evaluable endpoint data are not reported in the registry record.

General statistical explanation: when several outcomes or tests are examined, the chance of obtaining at least one apparently unusual result can increase if each is interpreted independently. Prespecified testing strategies can help clarify which findings are confirmatory and how other findings should be treated. Missing-data rules also matter because an analysis based only on observed measurements may differ from one that makes assumptions about unobserved outcomes.

Because neither the outcome estimates nor these analysis details are posted, readers cannot determine whether any reported statistical significance was adjusted for multiple testing, how missing endpoint measurements affected the result, or which participant population contributed to an analysis. These are not proof that a particular method was or was not used; the information is 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small bowel obstruction (8.3%), atrial fibrillation (8.3%), pneumonia (8.3%).

The adverse-event record lists 3 participants with serious adverse events among 12 at risk and 8 participants with other adverse events among 12 at risk. It reports 0 deaths. The listed serious-event terms are Small Bowel Obstruction, Atrial Fibrillation, and Pneumonia, each reported as 8.3%.

These figures describe the group in the registry record; they are not comparisons with another treatment. The record does not say whether participants with serious events also appear among those with other events, so the counts should not be added. The percentages are reported for the listed serious terms, but the record does not provide additional detail about how each term was counted or its timing.

General statistical explanation: an adverse-event count does not by itself describe event duration, severity beyond the listed category, recurrence, or exposure-adjusted frequency. Nor does a listed event establish that the intervention caused it. Interpretation of causality and comparative safety would require further design and clinical information that is not reported in the registry record.

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

The record establishes that NCT03413995 was a completed phase II, single-group study of rucaparib in men with metastatic hormone-sensitive prostate cancer and germline DNA-repair gene mutations. It specifies the primary PSA-response definition and provides selected adverse-event counts. Those details identify the clinical question and describe some aspects of the study design and safety reporting.

The primary outcome result is not reported in the registry record. No count of participants meeting the confirmed PSA-response definition, response estimate, or confidence interval is available. The secondary outcome results are also not reported. As a result, the posted information does not show the observed PSA response, progression outcomes, or objective response findings.

Even if a response count were available, the single-group design would not provide a randomized comparison with another treatment or a control condition. A descriptive outcome in the treated group cannot by itself establish what caused the outcome or how it compares with an alternative. The record does not report the study’s statistical analysis details needed to assess those questions.

The adverse-event figures provide descriptive counts and listed serious-event terms, not a comparative estimate of safety. The record does not provide exposure-adjusted event rates or information about overlap between the serious and other adverse-event categories. The reported 0 deaths is a count in the posted safety record; it does not resolve other safety questions.

General statistical explanation: a clinical endpoint, an estimate, and its uncertainty answer different questions. An endpoint defines what is measured; an estimate describes the observed result; an uncertainty measure indicates how precisely it is known. The registry record supplies the primary endpoint definition but not its result or precision. Accordingly, it supports a description of the study, not a conclusion about the magnitude, certainty, or comparative effect of rucaparib.

14. Why This Trial Matters Statistically

This trial addresses a narrowly defined clinical setting: metastatic hormone-sensitive prostate cancer in men with inherited mutations in DNA-repair genes, before androgen deprivation therapy. The study description frames the question as whether rucaparib is associated with PSA lowering earlier in the treatment course than the setting discussed in prior research. That makes the intended population and treatment context important when interpreting the design.

Statistically, the record illustrates the difference between a clear endpoint definition and a reported endpoint result. The primary measure specifies a threshold for PSA decline and requires confirmation, but the registry record does not provide the number of participants meeting that definition. Without the outcome estimate and its uncertainty, readers cannot assess how the observed data relate to the stated question.

The single-group design also matters. It can describe outcomes among participants receiving rucaparib, but it does not provide a concurrent randomized comparison. The design therefore limits what can be concluded about whether an observed change is attributable to treatment or how it compares with another approach.

The posted adverse-event counts offer some descriptive safety information, while leaving important context unreported, including event timing and exposure-adjusted rates. More broadly, the record lists several outcome measures but does not report their results or the analysis methods. This makes the study useful as an example of why endpoint definitions, comparison structure, analysis transparency, and results reporting all shape the strength of statistical interpretation.

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 main limitation for interpretation is that the registry record does not report the primary PSA-response result. It also does not report the results for the listed secondary outcomes. Without outcome estimates, readers cannot quantify the observed response or progression findings, or assess their precision.

The single-group design has no listed comparator. This prevents a randomized estimate of the difference between rucaparib and another treatment or control condition. The record also lists masking as none, and does not report how outcome assessment was conducted or whether any safeguards against assessment bias were used.

The endpoint timing is not fully clear: the timeframe is listed as 4 weeks, while confirmation requires a second measurement at least 4 weeks apart. The registry record does not explain the relationship between these statements. It also does not report the number of participants with evaluable PSA measurements, handling of missing data, analysis populations, or detailed outcome definitions beyond the primary endpoint description.

Safety information is limited to the posted counts, deaths, and listed serious-event terms. Event timing, duration, exposure-adjusted rates, overlap between categories, and comparative safety results are not reported. The registry record also does not report the protocol’s sample-size justification, statistical analysis plan, or any interim-analysis details. These gaps limit assessment of precision, bias, and the scope of the conclusions that could be supported by the full study.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations — NCT03413995.
• Registry record last updated 2024-10-16; status last verified 2024-09.
• Results first posted 2024-10-16.
• 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

NCT03413995 is a completed phase II, single-group trial sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. It enrolled 12 men with metastatic hormone-sensitive prostate cancer and germline DNA-repair gene mutations. The intervention was rucaparib 600 mg by mouth twice daily with continuous dosing. The study start is listed as 2018-09-10 and primary completion as 2023-11-08.

The primary endpoint was the count of participants with a PSA decline to at least 50% of baseline, confirmed by a second measurement at least 4 weeks apart. The primary result and secondary outcome results are not reported in the registry record. The adverse-event figures list 3 participants with serious adverse events, 8 with other adverse events, and 0 deaths. No comparator group or analysis entries are listed.