A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II) (NCT01482715), a non-randomized phase 1, phase 2 study. The primary outcome is Overall Response Rate Per RECIST Version 1.1 (Part 2).

2. Clinical Question

The broad clinical question was whether oral rucaparib could be administered and whether clinical activity could be assessed across the study’s different populations and phases. Part 1 focused on safety across dose levels and dosing regimens in patients with solid tumors. Parts 2A and 2B evaluated safety and clinical activity at the recommended Phase 2 dose in patients with a known deleterious germline or somatic BRCA mutation. Part 3 further evaluated pharmacokinetics of higher dose-strength tablets at that dose in patients with advanced solid tumors, including lymphoma, with evidence of a BRCA mutation.

These study aims cover distinct questions. Dose exploration and safety characterization in an early-phase cohort are not the same as estimating tumor response in the Part 2 population. The response endpoint applies to an eligibility-defined subset, not necessarily to every one of the 136 enrolled participants. Because there was no randomized comparator, the study cannot establish a relative effect against another treatment or against no treatment. Its registry description is best read as a study of dose, safety, pharmacokinetics, and preliminary activity, with the primary endpoint specifically concerned with confirmed tumor response in Part 2.

3. Trial Design

This was a completed Phase I/II, open-label, non-randomized study with sequential parts. The registry lists enrollment of 136 participants. The study had no masking, and its allocation is recorded as non-randomized. These features mean that participants and study staff were not masked to treatment, and the study did not assign participants randomly between a rucaparib group and a control group.

Part 1 evaluated safety at multiple doses and schedules of oral rucaparib in patients with solid tumors. The listed regimens included once-daily doses of 40, 80, 160, 300, and 500 mg, as well as twice-daily doses of 240, 360, 480, 600, and 840 mg, given in continuous 21-day cycles. Part 1 began with a dose-escalation evaluation period and could be followed by an optional treatment-extension period. The detailed duration or decision rules for those periods are not reported in the registry record.

Part 2A and Part 2B used 600 mg BID for 21-day cycles. Their stated purpose was to evaluate safety and clinical activity at the recommended Phase 2 dose in patients with a known deleterious BRCA mutation, either germline or somatic. Part 3 also used 600 mg BID for 21-day cycles and included additional single doses on Day -7 and Day 1 to assess the effect of food on pharmacokinetics. The registry describes Part 3 as a further pharmacokinetic evaluation in patients with advanced solid tumors, including lymphoma, and evidence of a BRCA mutation.

The study started in 2011-11, reached primary completion in 2019-03, and is listed as completed. The parts differed in objectives and populations, so their groups should not be treated as interchangeable. In particular, the dose cohorts in Part 1 were not randomized comparators for the Part 2 cohorts. The registry record does not report a control arm, randomization procedure, masking procedure, or the rationale used to select the sample size.

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.

Only the first 6 of 13 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Efficacy-Evaluable Population - all Part 2 patients who met eligibility criteria, received at least 1 dose of rucaparib, had measurable tumor lesions at baseline, and had at least 1 post-baseline disease assessment. 2 patients in Part 2A discontinued treatment due to an AE and did not have a post-baseline disease assessment.

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.

Only the first 6 of 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate Per RECIST Version 1.1 (Part 2), measured over Time from first dose to date of progression, up to approximately 8 months.

The primary endpoint was overall response rate per RECIST version 1.1 in Part 2. It counts patients whose tumor response was confirmed as a complete response or a partial response. A response had to be documented on a subsequent tumor assessment at least 28 days after the first response documentation. The registry specifies the unit as participants and describes the outcome as a count of participants.

In general, an overall response rate condenses tumor assessment into the proportion of an analysis population that meets the response definition. Requiring confirmation helps distinguish a response that persists to a later assessment from a single observation that may not be confirmed. RECIST provides standardized criteria for categorizing tumor changes, supporting consistent assessment within a study.

The endpoint’s stated analysis population was not all enrolled participants. It included Part 2 patients who met eligibility criteria, received at least 1 dose, had measurable tumor lesions at baseline, and had at least 1 post-baseline disease assessment. The registry notes that 2 patients in Part 2A discontinued treatment due to an adverse event and did not have a post-baseline assessment. The effect of those exclusions on the response estimate cannot be assessed from the record.

The registry gives the endpoint definition and timeframe but does not report the observed response count, response rate, confidence interval, or an associated statistical test. The posted endpoint therefore identifies what was intended to be measured, but the registry record does not provide the numerical primary result needed to quantify the observed response or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be discussed are limited by the information in the registry record. The record identifies the endpoint, its analysis population, and the overall design, but detailed analysis procedures are not reported in the registry record. General statistical explanations below clarify what such methods mean without assuming that a particular unreported method was used.

What does the primary endpoint count?

The primary endpoint is a binary classification at the participant level: a patient either meets the confirmed-response definition or does not. The specified event is a confirmed complete response or partial response under RECIST version 1.1, with confirmation on a later tumor assessment at least 28 days after initial response documentation. A response-rate estimate would summarize the fraction of the endpoint population classified as responders. The registry record gives no numerical estimate or responder count, so the actual result cannot be reconstructed or interpreted quantitatively.

In general, a confidence interval around a response rate expresses uncertainty about the underlying response proportion, given the observed data and the assumptions of the interval method. A narrower interval indicates greater precision, while a wider interval indicates less precision. It is not a range that guarantees the true value lies within it for an individual study. No confidence interval for the primary endpoint is reported in the registry record.

Why does the analysis population matter?

The primary endpoint population includes Part 2 patients meeting eligibility criteria, receiving at least 1 dose, having measurable tumor lesions at baseline, and having at least 1 post-baseline disease assessment. This is a selected analysis group. Requiring an assessment after treatment begins means that patients without a post-baseline assessment are not represented in that endpoint population. The registry specifically notes 2 Part 2A patients discontinued treatment due to an adverse event and lacked a post-baseline assessment. The record does not describe whether any additional exclusions occurred or how other incomplete assessments were handled.

In general, different analysis populations answer different questions. An analysis including all participants assigned to a study group can preserve the advantages of randomization in a randomized trial, while a population with sufficient follow-up may permit assessment of an endpoint that requires measurements. This study was not randomized, and the registry’s specified efficacy-evaluable population should therefore be interpreted according to its stated inclusion criteria rather than assumed to represent every enrolled participant.

What follows from a non-randomized design?

Randomization, in general, aims to make comparison groups similar on average with respect to measured and unmeasured factors. This study is recorded as non-randomized and has no control arm in the registry description. Differences between its dose cohorts or study parts may reflect population composition, eligibility, dose, study objective, follow-up, or other factors, as well as any treatment-related effects. The cohort data cannot be treated as a randomized comparison. The registry also describes open-label treatment, so participants and investigators were not masked.

How should safety counts be understood?

The safety information is presented as counts of participants at risk and affected, separately for serious and other adverse events, with deaths also listed. In general, counts are easier to interpret when the denominator, event definition, observation period, and whether participants can contribute more than one event are clear. The registry lists group sizes and affected counts, but does not provide all denominator and event-counting details for the listed serious-event terms. A participant count is not the same as a count of individual events, because one participant may experience more than one event; the record’s summary does not establish how each term’s percentage was calculated.

General comparisons of adverse-event percentages across cohorts require caution even when denominators are shown. Cohorts can differ in size, dose, duration of observation, clinical characteristics, or study part. An adverse event occurring during a study is not, by itself, proof that the study drug caused it. The non-randomized design and lack of a control group limit causal and comparative interpretation of the safety counts.

What do the planning assumptions mean?

The planning description states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the target effect as a stated fraction of the observed effect. In general, a significance level is a threshold used to control the probability of a false-positive result under a specified null model; a two-sided test considers departures in either direction. Equal allocation means assigning the same planned number of participants to each comparison arm. A normal approximation uses a normal distribution to approximate the sampling distribution of a statistic.

These are planning assumptions, not the study’s documented original design justification. The registry record does not report the sample-size rationale or the numerical planning results. The effect-size scenarios are not observed power. Power, in general, is a design-stage probability under an assumed effect and analysis model; it is not a measure of the probability that a finding is true. Since the primary response result is not reported in the registry record, the stated observed-effect basis cannot be evaluated from the registry information.

What is not documented?

The detailed statistical analysis plan, handling of multiplicity, interim analyses, missing-data methods, and confidence-interval procedures are not reported in the registry record. The record lists one analysis, but does not provide enough detail to establish the exact analysis method or its prespecified status. No unreported model, adjustment, or imputation method should be presumed. For interpretation, the available information supports the endpoint definition and design description, but not reconstruction of a complete statistical 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 (Part 2A)", "Rucaparib 600 mg BID (Part 2B)")
n      <- c(40, 12)
events <- c(25, 7)
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 (Part 2A)  40  25  62.5  45.8  77.3  47.0  75.8  46.9  75.8
ARM  Rucaparib 600 mg BID (Part 2B)  12  7  58.3  27.7  84.8  32.0  80.7  31.6  80.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response endpoint and multiple secondary outcomes. These include progression-free survival according to RECIST version 1.1 as assessed by the investigator, duration of response, overall survival in Part 2B, pharmacokinetic food-effect measures, and QTcF change from baseline. Considering multiple endpoints can increase the chance of at least one apparently notable result when many statistical tests are performed. In general, multiplicity procedures can adjust inference across tests or distinguish confirmatory from exploratory objectives. The registry record does not report a multiplicity strategy, the hierarchy of hypotheses, or whether any outcomes were formally designated as exploratory for statistical testing.

The record describes the primary endpoint population as eligible Part 2 patients who received at least 1 dose, had measurable baseline lesions, and had at least 1 post-baseline assessment. It also states that 2 Part 2A patients discontinued treatment due to an adverse event and had no post-baseline assessment. The method for handling missing tumor assessments, incomplete follow-up, or other missing outcomes is not reported in the registry record. No imputation method, sensitivity analysis, or missing-data assumption is described.

In general, missing outcome data can affect an estimate when the probability of having an observed assessment is related to a participant’s outcome or clinical course. Excluding patients without a post-baseline assessment may also change the population represented by an efficacy estimate. The record does not provide enough information to determine the direction or size of any such effect.

Interim analyses, stopping rules, and the statistical analysis plan are not reported in the registry record. The registry lists one analysis, but that fact alone does not establish whether the endpoint analysis was prespecified, when it was performed, or how secondary endpoints were handled. The record also does not report the sample-size justification. These omissions limit assessment of the analysis’s prespecification, multiplicity control, and robustness to missing data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant neoplasm progression (66.7%), lower respiratory tract infection (33.3%), seizure (33.3%), nausea (25.0%), non-cardiac chest pain (25.0%).

The adverse-event summary separates serious adverse events, other adverse events, and deaths by dose cohort and study part. For example, the Part 2A group lists 42 participants at risk for serious adverse events and 19 affected; it also lists 42 at risk for other adverse events and 41 affected, with 4 deaths. Part 3 lists 26 at risk and 9 affected for serious adverse events, 26 at risk and 26 affected for other adverse events, and 4 deaths. These are descriptive counts within the listed groups, not comparisons against a control group.

The record also lists serious-event terms and percentages, including malignant neoplasm progression at 66.7%, lower respiratory tract infection and seizure at 33.3% each, and nausea, non-cardiac chest pain, and cellulitis at 25.0% each. The denominator and calculation details for these percentages are not reported in the registry record. The listed terms should not be interpreted as percentages of all enrolled participants unless the registry explicitly defines that denominator.

In general, adverse events are events observed during a study and are not automatically attributable to the study drug. Seriousness is a classification distinct from severity. The non-randomized design, varied cohorts, and absence of a like-for-like control group prevent these counts from establishing comparative safety effects. Differences among cohorts may also reflect their different sizes, doses, study parts, or observation periods.

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

The registry record describes a multi-part early-phase study of oral rucaparib, with dose and schedule evaluation in Part 1, safety and preliminary clinical activity at the recommended Phase 2 dose in Part 2, and further pharmacokinetic evaluation in Part 3. The primary endpoint is clearly defined as confirmed overall response per RECIST version 1.1 in the Part 2 efficacy-evaluable population. That definition specifies the response categories, need for confirmation, and key population criteria.

What the record does not provide is the numerical primary endpoint result. The response count, response-rate estimate, and uncertainty interval are not reported in the registry record. Therefore, the endpoint definition alone cannot indicate how many participants responded, how large an observed response rate was, or how precisely it was estimated. It also does not support conclusions about a difference from another treatment, since the design has no randomized control group.

The reported safety counts document participants affected by serious and other adverse events and deaths across the listed cohorts. They provide a descriptive account of events recorded during the study. They do not, by themselves, identify which events were caused by rucaparib or establish how the observed counts compare with those under another treatment. The groups differ by dose and study part, so comparisons between them are not equivalent to a controlled safety analysis.

In general, a clinical trial result is most informative when the endpoint definition, analysis population, observed estimate, uncertainty, and analysis methods can all be assessed together. Here, the registry record gives the endpoint and population definition but lacks the numerical primary result and key analysis details. The most defensible reading is consequently about what was planned and how the study was structured, together with the safety counts that are listed—not a claim of efficacy or comparative benefit.

The study’s completed status and enrollment of 136 describe its conduct at a high level. They do not resolve the missing result information or establish that the primary question was answered with a particular degree of precision. Any planning scenarios are conditional illustrations based on stated assumptions, not observed power or evidence about the eventual response result.

14. Why This Trial Matters Statistically

This trial illustrates why study design and endpoint interpretation need to be considered together. Although the registry labels the study Phase I/II and gives a primary response endpoint, the study also contains distinct dose-exploration and pharmacokinetic components. The populations and objectives vary across parts. Treating all enrolled participants as if they contributed to one uniform efficacy question would obscure the registry’s specified Part 2 efficacy-evaluable population.

The response definition includes confirmation on a later tumor assessment, which makes the endpoint more specific than a single unconfirmed assessment. At the same time, the analysis population requires at least 1 post-baseline assessment. The registry notes 2 Part 2A patients who discontinued due to an adverse event and had no such assessment. This makes the relationship between treatment discontinuation, missing assessments, and the analyzed population relevant to statistical interpretation, although the record does not document the handling of missing data in detail.

The non-randomized, open-label structure is another important statistical feature. Multiple dose cohorts can support description of dose and safety experience, but without random assignment and a control group they do not provide a like-for-like comparison of treatment outcomes. Differences between cohorts should not be interpreted as treatment effects without accounting for the design and population differences.

Finally, a clearly defined endpoint is not a substitute for reporting its observed result. The registry record identifies the response measure but does not report its count, estimate, or precision. This distinction is useful when reading clinical trial records: a study can specify what it intended to measure while still leaving essential information for quantitative interpretation unavailable. The same caution applies to planning illustrations, which are assumptions for design scenarios rather than observed power or trial findings.

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 principal limitation for interpreting the primary endpoint is that its observed result is not reported in the registry record. The record gives the response definition and the efficacy-evaluable population but not the number of responders, response-rate estimate, confidence interval, or test result. Consequently, the primary endpoint’s magnitude and precision cannot be assessed from the available registry information.

The study was non-randomized, open-label, and sequential, with multiple cohorts and different purposes across parts. There is no randomized comparator for a causal treatment-effect estimate. Comparisons among dose groups or study parts would be confounded by differences in dose, population, eligibility, and objective. The registry does not report enough detail to determine whether follow-up duration or other features were comparable across cohorts.

The primary analysis population required a post-baseline disease assessment, and the registry identifies 2 Part 2A patients who discontinued treatment due to an adverse event without such an assessment. How missing outcomes were addressed beyond this population definition is not reported in the registry record. The potential influence of those exclusions, and of any other missing assessments, therefore cannot be evaluated.

The detailed statistical analysis plan, sample-size justification, multiplicity strategy, interim analyses, and stopping rules are not reported in the registry record. Although secondary outcomes are listed, the record does not describe how inferential claims across them were controlled. The serious-event term percentages are given without denominator and calculation details. These limitations restrict both efficacy interpretation and quantitative assessment of safety. The record’s completed status and enrollment count do not compensate for the absence of outcome estimates or analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Oral Rucaparib in Patients With a Solid Tumor (Phase I) or With gBRCA Mutation Ovarian Cancer (Phase II) — NCT01482715.
• Registry record last updated 2023-06-09; status last verified 2023-06.
• Results first posted 2020-12-08.
• 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 record describes a completed, open-label, non-randomized Phase I/II study of oral rucaparib, with enrollment of 136 participants. It included dose and schedule evaluation in Part 1, 600 mg BID regimens in Parts 2A and 2B, and a pharmacokinetic food-effect component in Part 3. The primary endpoint was confirmed overall response per RECIST version 1.1 in the Part 2 efficacy-evaluable population.

The record defines the endpoint but does not report its responder count, response-rate estimate, or precision. It lists serious and other adverse-event counts and deaths by cohort, alongside selected serious-event terms and percentages. Because the study was non-randomized and had no control arm, the cohorts are not like-for-like treatment comparisons. The detailed statistical plan, missing-data handling, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record.