PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery (NCT00365053), a na phase 2 study. The primary outcome is Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

2. Clinical Question

In practical terms, the study asked whether tumor assessments in this group met the prespecified response categories after second-line belinostat treatment. A complete response required disappearance of all target lesions. A partial response required at least a 30% decrease in the sum of the longest diameters of target lesions. The endpoint combines these categories as overall response. It is a measure of tumor shrinkage, not a comparison of survival or quality of life between treatment strategies.

The registry also lists overall survival, progression-free survival, toxicity, apoptosis by TUNEL assay, and histone acetylation as secondary outcomes. It does not report results for those outcomes in the information available for this study.

3. Trial Design

This was a phase II study of belinostat as second-line therapy for malignant pleural mesothelioma. It used a single-group design, with no random allocation and no masking. The registry lists the allocation as NA and describes one treatment group. As a result, the study can describe outcomes among participants who received the study treatment, but it does not provide a randomized control group for estimating a treatment contrast.

The registry records enrollment of 13 participants and lists the study status as completed. The recorded start was 2006-06 and primary completion was 2009-03. The National Cancer Institute (NCI) is listed as sponsor. These dates and status describe the registry entry; they do not establish when each participant began or completed treatment.

The treatment description specifies PXD101, identified in the intervention listing as belinostat. Participants were scheduled to receive it intravenously at 1000 mg/m2 over 30 minutes on days 1-5. Courses were repeated every 21 days for up to 6 courses, unless disease progression or unacceptable toxicity occurred. The record does not give participant-level exposure, the number of courses actually received, or reasons for stopping treatment.

The primary outcome was objective tumor response by RECIST v1.0, assessed using CT, MRI, or X-ray, over a timeframe of up to 3 years. The registry lists six outcome measures in total, including secondary measures of overall survival, progression-free survival, toxicity, apoptosis, and histone acetylation. Their analysis methods and results are not reported in the registry record.

Because the study is single-group and unmasked, its design is suited to reporting observed outcomes within the enrolled group, not to separating treatment effects from other explanations such as disease course, patient selection, or assessment variation. The registry record does not report a protocol-level sample-size justification or a statistical analysis plan.

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 Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee, measured over Up to 3 years.

The primary endpoint was objective tumor response rate: the percentage of participants classified as having either a complete response or a partial response under RECIST v1.0. A complete response meant disappearance of all target lesions. A partial response meant at least a 30% decrease in the sum of the longest diameters of target lesions. Target lesions were assessed by CT, MRI, or X-ray, and overall response was defined as complete response plus partial response. The assessment timeframe was up to 3 years.

Response rate is a binary outcome at the participant level: each assessed participant is classified as meeting or not meeting the response definition. It can provide a direct description of how often measured tumors met these shrinkage criteria in the study group. It does not by itself describe how long a response lasted, whether disease later progressed, or whether survival differed from what would have occurred without treatment.

The endpoint definition is reported, but the number of participants with complete or partial response, the response rate, and its confidence interval are not reported in the registry record. The number evaluated for this endpoint and the handling of participants without an evaluable assessment are also not reported. Therefore, the response endpoint can be described from the registry definition, but its observed result and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: whether a participant met the RECIST definition of objective response. For this kind of endpoint, the response rate is ordinarily calculated as the proportion of assessed participants classified as having a complete or partial response. The registry specifies the response categories and imaging modalities, but does not report the observed numerator, denominator, rate, or confidence interval. The response calculation therefore cannot be reconstructed from the record.

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity. For a response rate, it would help readers judge how precisely the observed proportion estimates the response frequency in a broader population similar to the study group. Narrower intervals indicate greater precision; wider intervals indicate less precision. A confidence interval does not remove the limitations of a single-group design, and it cannot be interpreted as a comparison with an untreated or alternative-treatment group. No confidence interval for the primary endpoint is reported in the registry record.

What does the single-group design allow?

With a single treatment group, the analysis can describe outcomes observed among participants receiving belinostat. There is no randomized comparator to estimate a between-group difference. A response observed after treatment cannot, on its own, show what would have happened to the same participants under another strategy. General statistical interpretation therefore distinguishes a within-group outcome from a comparative treatment effect. This distinction remains important regardless of whether an outcome is expressed as a percentage or as a time-to-event measure.

How should the planning illustration be read?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not the design features of this single-group study. The illustration is not an observed power calculation and does not establish the trial's original sample-size rationale. The record does not report a protocol sample-size justification. Since the primary response result is not reported, the observed effect underlying such an illustration is not available in the registry information, and no planning participant count should be inferred from the assumptions alone.

In general, sample-size calculations depend on assumptions about the effect to detect, the variability or event frequency, the significance threshold, and the desired power. Changing the assumed effect changes the planning requirement. A planning calculation is not evidence that a study had a particular probability of obtaining a statistically significant result after it was conducted. The registry's planning assumptions should therefore be kept separate from observed trial findings.

What can be concluded about analysis choices?

The registry lists no analyses. It does not report a statistical analysis plan, a method for calculating the response rate, a confidence interval method, or a hypothesis test for the primary endpoint. It does not report adjustment for covariates or describe any interim analyses. These details are not reported in the registry record, so no particular approach should be presumed.

General methodological considerations include defining the population to be analyzed, setting rules for missing or unevaluable assessments, and specifying how outcomes are summarized. For time-to-event outcomes such as overall survival or progression-free survival, analysts also need to define the time origin, event, censoring rules, and analysis method. The registry lists these outcomes but does not report those details or their results.

Multiplicity is another general consideration when several outcomes or analyses are examined. Testing multiple hypotheses can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry lists a primary endpoint and several secondary outcomes but does not report a multiplicity strategy. Without analysis results or a statistical plan, readers cannot determine whether or how multiplicity was handled.

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("Treatment (Belinostat)")
n      <- c(13)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Belinostat)  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies objective tumor response as the primary outcome and lists secondary outcomes of overall survival, progression-free survival, toxicity, apoptosis by TUNEL assay, and histone acetylation by IHC and Western blotting. It does not report whether the outcome hierarchy was prespecified in a statistical analysis plan, whether any secondary outcomes were considered exploratory, or whether adjustments for multiple testing were planned. These details are not reported in the registry record.

In general, examining several outcomes creates multiplicity: the more statistical questions considered, the more opportunities there may be for chance findings. A prespecified strategy can help readers understand which results are confirmatory and how uncertainty should be interpreted. The registry information does not state whether such a strategy was used, and it lists no analyses.

The primary endpoint definition describes response categories and imaging modalities, but the record does not explain how missing imaging, unevaluable scans, or incomplete follow-up were handled. The number included in the primary endpoint denominator is not reported. The analysis population is also not described; for example, the record does not say whether all enrolled participants or only those with an evaluable assessment were included in the response calculation.

For the secondary time-to-event outcomes, rules for censoring and follow-up are not reported. No interim analyses or stopping rules are reported, and none should be assumed. In general, these details affect how estimates are formed and which participants contribute information. Their absence limits assessment of the reliability and potential bias of any outcome estimate, but the record does not provide enough information to determine how missing data or multiplicity affected this study.

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: dyspnea (15.4%), supraventricular tachycardia (7.7%), chest pain (7.7%), death (7.7%), back pain (7.7%).

The registry safety summary lists 13 participants at risk for serious adverse events and 3 participants affected in the belinostat treatment group. It also lists 13 participants at risk for other adverse events and 13 affected. The record reports 1 death. These entries describe the registry's group-level safety counts; they do not establish that an event was caused by belinostat.

The most frequently listed serious adverse event term is dyspnea at 15.4%. Supraventricular tachycardia, chest pain, death, back pain, and hypoxia are each listed at 7.7%. These percentages are reported event figures, not comparative risks, and the registry summary does not provide a control group for comparison. It also does not give context about event timing, duration, severity grading beyond the serious-event classification, or attribution to treatment.

Serious adverse events and other adverse events are separate summary categories. The figures should not be added together, treated as mutually exclusive participant groups, or interpreted as proof of causation. The death entry is a reported safety outcome; the registry information does not state its cause or establish a treatment relationship.

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

The record establishes that a phase II study evaluated belinostat as second-line therapy in a single group of patients with malignant pleural mesothelioma. It provides the treatment schedule and defines the primary response endpoint using RECIST v1.0. It also lists secondary outcomes and provides selected serious adverse event summaries. Those details describe the study's scope and some recorded safety information.

The record does not report the primary response result, its denominator, or an uncertainty interval. It likewise does not report results for the listed survival or biomarker outcomes. As a result, the registry information cannot show how often participants met the response definition, how long any response lasted, or what the survival outcomes were.

Even a reported response percentage from this design would describe the enrolled treatment group rather than establish a causal benefit. With no randomized comparator, there is no direct estimate of how outcomes differed from another treatment or from no treatment. The record also does not report enough about missing assessments, outcome analysis, or participant-level follow-up to assess those issues.

The safety summary records adverse events and a death, but it does not establish attribution. The listed percentages and participant counts should be read as descriptive entries, not as proof that treatment caused or prevented an event. A single-group registry summary also cannot provide a comparative safety estimate.

Overall, the registry record is informative about the study design, planned treatment, endpoint definitions, and selected safety entries. It does not supply the efficacy results or analysis details needed to judge the size or precision of any tumor response estimate. These limits mean the record cannot support a conclusion about treatment effectiveness.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an outcome estimate are different kinds of information. RECIST v1.0 gives a structured way to classify tumor response, including definitions for complete and partial response. That structure can make outcome assessment more interpretable, but it does not tell readers what happened in the study unless the response count, denominator, and estimate are also reported.

The study also highlights the inferential limits of a single-group design. Outcomes observed among participants receiving a treatment can be described, but without a comparator they do not quantify a treatment contrast. This distinction is central to biostatistical interpretation: a within-group response rate and a causal estimate comparing treatment strategies answer different questions.

Registry completeness matters as well. The record identifies outcomes and a treatment schedule, yet it does not report primary efficacy results, analysis methods, missing-data rules, or multiplicity handling. Without those elements, readers cannot judge the numerical response result, its precision, or the robustness of analyses. The safety entries remain useful as descriptive reports, but do not establish attribution or comparative risk.

The study is therefore a useful case for separating protocol concepts from reported evidence. The endpoint is clearly defined, while the actual endpoint result is unavailable in the registry record. Careful statistical reading keeps those two details distinct and avoids treating an outcome definition, a planning assumption, or an adverse-event listing as a substitute for a reported comparative result.

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 primary limitation of the available registry information is that it does not report the primary endpoint result. Although the RECIST response definition and assessment timeframe are described, the response count, denominator, rate, and confidence interval are not reported. The same record does not provide results for the listed secondary outcomes, so efficacy and biomarker outcomes cannot be assessed from it.

The single-group, unmasked design has no control group and does not support a direct randomized treatment comparison. The record also does not report participant-level treatment exposure, the number of courses received, imaging-evaluation completeness, or reasons for treatment discontinuation. Missing-data rules and the analysis population are not reported, leaving uncertainty about who contributed to any endpoint analysis.

The registry does not describe the statistical analysis plan, sample-size justification, interim analyses, or multiplicity procedures. It lists no analyses. These omissions prevent readers from evaluating whether the reported outcome definitions were implemented as planned or how inferential uncertainty was handled. The safety summary is limited to group-level counts and selected terms; it does not provide event timing, attribution, or comparative safety information.

These limitations concern the information reported in the registry record and should not be taken as proof that the underlying study had no further documentation. The record does not include those details, so conclusions should remain limited to the design, definitions, and safety entries it contains.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery — NCT00365053.
• Registry record last updated 2018-06-07; status last verified 2018-05.
• Results first posted 2014-12-29.
• 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

NCT00365053 is a completed phase II, single-group study sponsored by the National Cancer Institute (NCI), with enrollment of 13. It evaluated belinostat, identified as PXD101, as second-line therapy for malignant pleural mesothelioma. The recorded study start was 2006-06 and primary completion was 2009-03.

The treatment schedule was intravenous belinostat at 1000 mg/m2 over 30 minutes on days 1-5, repeated every 21 days for up to 6 courses unless progression or unacceptable toxicity occurred. The primary endpoint was RECIST v1.0 objective tumor response assessed by CT, MRI, or X-ray over up to 3 years. The response result and statistical analysis details are not reported in the registry record.

The registry lists overall survival, progression-free survival, toxicity, apoptosis, and histone acetylation as secondary outcomes. Its safety summary reports 3 participants affected by serious adverse events, 13 affected by other adverse events, and 1 death in the treatment group; event attribution is not reported.