A Study of Olaparib With Concomitant Radiotherapy in Locally Advanced/Unresectable Soft-tissue Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Olaparib With Concomitant Radiotherapy in Locally Advanced/Unresectable Soft-tissue Sarcoma (NCT02787642), a na phase 1 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

The registry describes a phase Ib study of olaparib with concomitant radiotherapy in locally advanced or unresectable soft-tissue sarcoma. It is listed as completed, with a registry enrollment of 41. The recorded start is 2016-01 and the primary completion is 2021-10. These registry dates describe the study record; they do not supply a result for the primary endpoint.

The design is single-group, with no masking and allocation listed as not applicable. The primary endpoint description says that the study assessed four olaparib dose levels: 25 mg, 50 mg, 100 mg, and 150 mg, each in association with radiotherapy. The record describes oral twice-daily olaparib, starting one week before radiotherapy and continuing until its last day; the schedule also refers to a 7.5-week treatment period. It mentions that olaparib could continue beyond that period, but the available description is truncated and does not fully specify that circumstance.

Because there is no separate randomized control group, the different dose groups do not provide a like-for-like comparison of olaparib with no olaparib or of radiotherapy with no radiotherapy. Dose-group counts can describe what was recorded within each group, but they cannot by themselves isolate a treatment effect. The registry record does not report the dose-escalation rules, the rationale for the selected dose levels, or a statistical analysis plan.

Secondary outcomes include non-progression and objective response at 6 months under RECIST 1.1, best response under treatment, progression-free survival under RECIST 1.1, overall survival, and the Musculoskeletal Tumor Society functional score. The record lists eight outcome measures but does not provide results for these secondary outcomes in the information.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dose escalation study assessing four doses level of Olaparib (25mg, 50mg, 100mg, 150mg) in association with concomitant radiotherapy.

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 Who Experienced Dose-Limiting Toxicities (DLTs), measured over Until to six weeks after end of radiotherapy.

The primary endpoint is the number of participants who experienced dose-limiting toxicities (DLTs). It is a count endpoint: it records participants meeting the DLT definition, rather than measuring the severity of every adverse event or the total number of events. The observation period is described as beginning on the first day of treatment and continuing up to six weeks after the end of radiotherapy.

The registry definition requires an event or laboratory abnormality to occur during that observation period, to be considered at least possibly related to the treatment strategy, to be unrelated to disease, disease progression, inter-current illness, or concomitant medications, and to meet specified criteria graded according to NCI CTCAE v4.0. The criteria are referenced as being in the protocol, but their full detail is not present in the registry record.

In a dose-escalation study, a prespecified toxicity endpoint can guide assessment of whether a dose level is tolerable enough to investigate further. That is the general role of a DLT endpoint; it does not alone summarize all aspects of safety, tumor response, or longer-term outcomes. The observed primary-endpoint count and its interpretation are not reported in the registry record, so the endpoint’s result cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with a qualifying DLT. A count answers how many participants met a definition; it is not the same as the number of separate toxic events, since one participant may experience more than one event. The registry title and description specify the participant count as the endpoint, but the observed count is not reported in the registry record.

For a count to be interpretable, it is usually read together with the number of participants who could have experienced the event during the relevant observation period. That denominator makes clear how much information the count represents. In this study, the registry enrollment is 41, but the denominator for the primary endpoint at each dose level and the number completing the observation window are not reported in the registry record. Enrollment should not be assumed to be the analysis denominator.

A confidence interval is a range of values compatible with the data under a specified statistical model. In general, it communicates precision: a wider interval indicates greater uncertainty, while a narrower interval indicates more precision under that model. No confidence interval for the DLT endpoint is reported in the registry record. Without the endpoint count, denominator, and a stated interval method, a numerical precision statement cannot be made.

Counts from small dose groups can be especially uncertain. A change in the status of one participant can materially alter the descriptive count in a small group. This is a general property of sparse data, not a conclusion about what happened in this study. The registry record does not state a model or inferential procedure for comparing DLT counts across dose levels.

In general, a dose-escalation design uses accumulating safety information to inform decisions about subsequent dose levels. The statistical interpretation depends on the prespecified escalation rules, dose-limiting criteria, observation windows, and decision thresholds. The record supplies a DLT definition and four dose levels, but the escalation algorithm, decision thresholds, and statistical plan are not reported in the registry record. It would therefore be inappropriate to infer how escalation decisions were made or what dose was selected.

The record’s DLT definition includes both clinical events and laboratory abnormalities, with conditions about timing, possible relation to the treatment strategy, and alternative explanations. Such criteria distinguish a DLT from any adverse event recorded during follow-up. The definition also refers to criteria in the protocol and grading according to NCI CTCAE v4.0. The full criteria are not reported in the registry record, which limits independent reconstruction of which events qualified.

Over-dispersion is a general issue in count data: observed counts may vary more than a simple statistical model assumes, for example when event rates differ across participants or settings. If a count model assumes less variability than is present, its uncertainty estimates may be too optimistic. The registry record does not report a count model, model checks, or an over-dispersion assessment. Since the primary endpoint is stated as a participant count and no analysis is listed, no claim about such modeling can be made for this trial.

For binary outcomes such as the listed response outcomes, a general analysis would distinguish the number meeting the outcome from the number assessed, and might report an estimate with an interval to convey uncertainty. For time-to-event outcomes such as progression-free survival or overall survival, general methods can account for differing follow-up and censoring. Those descriptions explain common statistical approaches; they are not claims that these analyses were performed in this study. The registry record lists those outcomes but does not report their results or analysis methods.

Where results are recalculated from posted summary statistics, such calculations are simple unadjusted re-calculations and do not replace a sponsor’s own analysis. No recalculated primary endpoint result or sponsor analysis is reported in the registry record. Any sample-size figures used for planning are illustrations, not observed power. The registry record does not report the trial’s own sample-size justification, and no trial-specific power conclusion can be drawn from enrollment alone.

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("Olaparib 25mg + Radiotherapy", "Olaparib 50mg + Radiotherapy", "Olaparib 100mg + Radiotherapy", "Olaparib 150mg + Radiotherapy")
n      <- c(4, 7, 10, 3)
events <- c(1, 1, 0, 1)
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  Olaparib 25mg + Radiotherapy  4  1  25.0  0.6  80.6  4.6  69.9  5.3  71.6
ARM  Olaparib 50mg + Radiotherapy  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  Olaparib 100mg + Radiotherapy  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Olaparib 150mg + Radiotherapy  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes, including non-progression and objective response at 6 months under RECIST 1.1, best response under treatment, progression-free survival, overall survival, and the Musculoskeletal Tumor Society functional score. When several outcomes are examined, multiplicity is a general concern: the chance of at least one apparently notable finding can increase as more hypotheses are tested. A prespecified hierarchy or adjustment can help define how such results should be interpreted.

The registry record does not report a multiplicity strategy, a hierarchy among the outcomes, or an analysis plan specifying which comparisons were confirmatory. It lists eight outcome measures, but the number of analyses is recorded as zero. The results and statistical analyses for the listed secondary outcomes are not reported in the registry record. No claim about multiplicity adjustment or confirmatory status can therefore be made.

Missing data can affect estimates when outcome status is unavailable or follow-up ends before an assessment. A general analysis should state how missing observations were handled and whether the assumptions about missingness are plausible. The registry record does not report endpoint-specific missingness, loss to follow-up, imputation, or sensitivity analyses.

The record also does not define analysis populations, such as which participants were included in each endpoint analysis, or explain how participants with incomplete treatment or follow-up were handled. The enrollment figure alone does not identify the denominator for any outcome. These omissions limit assessment of whether the reported safety counts or any unreported outcomes represent all enrolled participants, participants treated, or a different analysis group.

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: cutaneous necrosis (33.3%), dyspnea (20.0%), erysipelas (20.0%), anemia (20.0%), radioepithelite (20.0%).

The registry’s serious adverse event entries give, by olaparib dose with radiotherapy, the number listed as at risk and the number affected. The entries are 4 of 5 for 25 mg, 5 of 7 for 50 mg, 5 of 11 for 100 mg, and 1 of 3 for 150 mg. These are descriptive counts, not a controlled comparison. The dose groups are not randomized like-for-like groups, and the record does not report an inferential comparison between them.

The registry also lists other adverse events and deaths by group: 5 of 5 and 3 deaths at 25 mg; 7 of 7 and 4 deaths at 50 mg; 11 of 11 and 3 deaths at 100 mg; and 3 of 3 and 1 death at 150 mg. The record does not establish that deaths were caused by treatment, and the death counts should not be read as treatment-related deaths. The meaning of “at risk” and the follow-up completeness for each safety category are not further described in the registry record.

Serious adverse events are not necessarily DLTs. The DLT endpoint has separate timing and attribution criteria, and the registry does not link these safety counts to the primary endpoint. The listed serious-event terms include cutaneous necrosis at 33.3%, and dyspnea, erysipelas, anemia, radioepithelite, and massive blood hemorrhage at 20.0% each. The registry record does not specify the denominator behind these term percentages in the information available, so they should be read as recorded labels rather than rates across a clearly identified population.

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

This study addresses the feasibility and safety question embodied by a phase Ib dose-escalation design: how olaparib given with radiotherapy was assessed across dose levels in locally advanced or unresectable soft-tissue sarcoma. The registered primary endpoint is a count of participants with DLTs during a defined observation period. That endpoint is relevant to dose assessment, but its observed result is not reported in the registry record.

The registry enrollment of 41 and the dose-specific safety counts give some context for the study record, but they do not substitute for the primary endpoint result or a complete analysis. Serious adverse event counts, other adverse event counts, and deaths are distinct summaries. They do not identify which participants met the DLT definition, establish event causality, or provide a comparison against radiotherapy alone.

The single-group design has no randomized comparator. It cannot by itself determine how outcomes would have differed without olaparib or without radiotherapy. Nor can differences across dose groups be taken as causal estimates, because the registry does not describe random allocation to those groups and specifically lists the design as single-group.

The record lists tumor response, progression, survival, and functional outcomes, but does not report their results. It also does not report confidence intervals, p-values, detailed analysis populations, or missing-data handling. As a result, the available registry information cannot establish the magnitude or precision of any efficacy outcome, nor support a treatment recommendation.

In general, a small early-phase dose-escalation study can inform further study design by describing observed safety at investigated doses. That general purpose should not be confused with proof of efficacy or a precise estimate of uncommon harms. In this case, the missing DLT result and absent analysis details limit even the direct statistical interpretation of the registered primary question.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a dose-escalation question and a controlled treatment-effect question. Its primary endpoint is a participant count of DLTs, and its single-group structure evaluates olaparib alongside radiotherapy across four dose levels. It is not a randomized comparison of the combination against a control treatment.

That distinction matters because descriptive safety counts and causal comparisons answer different questions. Counts can describe what the registry records within each dose group. A causal estimate would require a suitable comparison and a design and analysis that address differences between groups. The registry record does not provide such a control group or a randomized allocation scheme.

The endpoint definition also illustrates why outcome labels matter. A serious adverse event is not automatically a DLT: the primary endpoint applies timing, attribution, alternative-cause, and grading criteria. Keeping those definitions separate prevents safety summaries from being mistakenly treated as the primary result.

The record’s missing primary endpoint result is a central interpretive limitation. The study title and design identify what was investigated, and the safety entries offer descriptive counts, but the registered DLT count is not reported. Without it, the principal dose-limiting toxicity question cannot be answered from the registry record. Missing analysis methods and endpoint-specific denominators further limit precision and reproducibility.

More broadly, the case demonstrates that registry enrollment, outcome definitions, and safety summaries are not interchangeable with a complete statistical report. Clear denominators, outcome results, uncertainty estimates, analysis populations, and prespecified methods are needed to judge how much evidence a result contains. The registry record does not report those details for the primary endpoint.

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 important limitation for statistical interpretation is that the observed primary endpoint count is not reported in the registry record. The endpoint definition is described, but no result is available to quantify DLT occurrence. The record also does not report dose-specific primary endpoint denominators, so enrollment cannot be used as a substitute for the number assessed at each dose.

The full DLT criteria are not reproduced; the description refers to criteria in the protocol and grading according to NCI CTCAE v4.0. The dose-escalation rules and statistical plan are not reported. This prevents reconstruction of the decision process or assessment of whether the endpoint definition and escalation procedure were applied as planned.

The study is single-group, with no randomized control group. Dose-level safety summaries are not like-for-like comparisons, and they cannot separate treatment effects from differences among participants or other factors. The record does not provide baseline characteristics or details that would support an adjusted comparison.

Although safety counts are listed, follow-up completeness and the meaning of the at-risk figures are not further detailed. The record does not report whether events were judged treatment-related, and serious adverse events cannot be assumed to satisfy the DLT definition. The listed deaths do not establish cause.

Secondary outcome results, confidence intervals, p-values, missing-data procedures, and analysis populations are not reported in the registry record. The planned sample-size rationale is also not reported. These gaps restrict assessment of precision, missingness, multiplicity, and the relationship between enrollment and analyzed outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Olaparib With Concomitant Radiotherapy in Locally Advanced/Unresectable Soft-tissue Sarcoma — NCT02787642.
• Registry record last updated 2026-02-25; status last verified 2026-02.
• Results first posted 2026-02-25.
• 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 NCT02787642 as a completed phase Ib, single-group study of olaparib with concomitant radiotherapy for locally advanced or unresectable soft-tissue sarcoma. Enrollment is listed as 41. The study assessed four olaparib dose levels: 25 mg, 50 mg, 100 mg, and 150 mg.

The primary outcome was the number of participants with dose-limiting toxicities during the period from first treatment through up to six weeks after radiotherapy ended. The registry record does not report the observed primary endpoint count or its analysis. Serious adverse event, other adverse event, and death counts are listed by dose group, but they do not replace the DLT result or establish causality.

Secondary outcomes include response, progression, survival, and functional score measures. Their results, analysis populations, missing-data handling, and statistical plan are not reported in the registry record. The single-group design does not provide a randomized control comparison.