Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II) (NCT00700336), a randomized phase 1, phase 2 study. The primary outcome is 4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel phase I/II study sponsored by CanBas Co. Ltd. The registry lists an enrollment of 69 and records the study as completed. The study began in 2008-05, with primary completion in 2012-07. Those registry-level details describe the study as a whole; they do not establish how many participants were included in each phase or in the primary endpoint analysis.

The phase I portion was a dose-finding study. It evaluated escalating doses of CBP501 with full-dose cisplatin and pemetrexed in patients with advanced solid tumors meeting the eligibility description. The maximum tolerated dose was to be determined from dose-limiting toxicities during the first treatment cycle, and pharmacokinetics of the combination were to be assessed. The arm description states that the dose selected for phase II was determined by 6 patients using a 3+3 approach. The registry does not report the dose selected or the phase I pharmacokinetic findings.

The phase II portion evaluated the selected CBP501 dose in previously untreated, unresectable malignant pleural mesothelioma. The registry describes random assignment in a 2:1 ratio to pemetrexed, cisplatin, and CBP501 or to pemetrexed and cisplatin. Histology and performance status were specified as stratification factors. Although the study is labeled randomized, masking is listed as none; participants and study staff therefore were not described as blinded in the registry.

The recorded overall enrollment should not be read as the analysis population for the phase II primary endpoint. Phase I and phase II addressed different objectives and populations. The number assigned to each phase, the number analyzed for the endpoint, and the disposition of participants are not reported in the registry record.

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 4M PFS Rate of Patients With Previously Untreated, Unresectable Malignant Pleural Mesothelioma (MPM) Treated With CBP501, Pemetrexed and Cisplatin, measured over End of study.

The primary endpoint was the four-month progression-free survival rate in the CBP501 combination group among previously untreated patients with unresectable malignant pleural mesothelioma. The registry’s description defines the relevant status at four months as being free of both progression and death. This is a binary status at a specified time: each participant would be classified according to whether progression or death had occurred by that point.

A fixed-time progression-free survival rate can summarize the proportion of a study group that remains alive without documented progression at a clinically relevant assessment time. It combines information about disease progression and death rather than describing either outcome alone. It is not the same as median progression-free survival, which concerns the time at which an estimated survival curve reaches a particular level, and it is not an overall survival endpoint.

The registry states a planned decision threshold: at least 23 patients, corresponding in the record to more than 54%, were to be free of progression and death at four months for the regimen to be considered for further evaluation in this indication. This is a planned criterion, not an observed result. The registry record does not report the observed number meeting the endpoint, the corresponding rate, a confidence interval, or a comparison of this endpoint between the randomized arms. It also does not report the endpoint’s assessment rules or handling of participants without an evaluable four-month status.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study combines two different statistical tasks. Phase I was dose finding: its purpose was to identify a dose for subsequent study using dose-limiting toxicities during the first treatment cycle. Phase II was a randomized evaluation of the selected CBP501 dose with pemetrexed and cisplatin against pemetrexed and cisplatin alone. These tasks have different objectives, populations, and interpretations. A dose-finding result does not itself answer the phase II efficacy question.

What does randomization contribute?

Randomization assigns participants to treatment groups by chance. In general, this helps make groups comparable with respect to both measured and unmeasured characteristics, on average, and provides a basis for estimating a treatment contrast. It does not guarantee that the groups are identical, and it cannot replace reporting the outcomes and analysis. The registry describes phase II randomization in a 2:1 ratio and stratification by histology and performance status. It does not report how the randomization sequence was generated, how assignment was concealed, or whether the analysis accounted for the stratification factors.

The study is listed as open label. In general, lack of masking can influence treatment delivery, participant reporting, clinical assessment, or decisions about whether progression has occurred. The potential relevance depends on the outcome and assessment procedures. The registry does not report details of assessment blinding or safeguards against assessment bias, so their use cannot be assumed.

How should the primary endpoint be understood?

The four-month progression-free survival endpoint is a fixed-time binary measure: the relevant status is whether a participant is alive and without progression at the specified time. A rate for a group would summarize the frequency of that status. A comparison between randomized groups would require group-specific results and a defined statistical method. The posted record supplies neither the observed endpoint counts nor an analysis estimate, so it does not permit a recalculation or interpretation of a treatment contrast.

The registry’s planned rule uses a threshold for the CBP501 group: at least 23 patients, or more than 54%, free of progression and death at four months. Such a rule is a decision criterion specified in the outcome description. It is not a confidence interval, a significance test, or evidence that the criterion was met. The record does not report the observed value against which the threshold could be assessed.

What would a confidence interval add?

As a general statistical concept, a confidence interval expresses uncertainty around an estimate. For a rate, it indicates how imprecisely the underlying rate is estimated from the observed participants, given the chosen method. For a difference between randomized groups, it can show both the range of plausible contrasts and whether the estimate is precise enough to distinguish among materially different possibilities. A point estimate alone would not show this uncertainty; however, no point estimate or interval for the primary endpoint is reported in the registry record.

Why do analysis populations and missing outcomes matter?

In a randomized study, an analysis based on assigned groups generally preserves the comparison created by randomization. Other analysis populations can answer different questions and may introduce bias if inclusion depends on events after assignment. The registry does not state which analysis population was used for the primary endpoint. It also does not report the number of participants with an assessable four-month outcome or how participants with missing assessments were treated. In general, missing outcome data can affect a rate when the likelihood of missingness is related to prognosis or treatment experience. Different handling assumptions can lead to different estimates.

What can the sample-size illustration say?

Any sample-size figures associated with planning are illustrations based on the observed effect under stated assumptions, not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. Such calculations describe hypothetical future planning under assumptions, not the probability that this completed study found an effect. Because the registry does not report the primary endpoint analysis and does not provide an observed effect for that endpoint, the illustration cannot serve as evidence for the trial’s result. The registry’s planned phase II allocation was 2:1, whereas the sample-size illustration assumes equal allocation; those are distinct design and planning descriptions.

Over-dispersion is a general concern when outcome variability exceeds what a statistical model assumes. In a binary endpoint, model assumptions affect standard errors and intervals; a mismatch can make uncertainty estimates too narrow or too wide. The registry record does not report a model-based endpoint analysis, so there is no basis for determining whether over-dispersion was assessed or relevant to the sponsor’s analysis. The record also does not report interim analyses, a statistical analysis plan, a sample-size justification, or the sponsor’s endpoint analysis methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, but it also notes that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not explain the categories or time points in enough detail to reconstruct the planned analysis. It does not report whether a single primary hypothesis was selected, whether multiple comparisons were planned, or whether any multiplicity adjustment was used. Without that information, the false-positive risk across any collection of tests cannot be assessed.

Missing endpoint data are another unresolved issue. The record does not give the number of participants with an evaluable four-month status, the reasons for unavailable assessments, or the method used to handle missing outcomes. In general, excluding participants with missing outcomes can bias a result if missingness is related to treatment or prognosis. Imputation and other missing-data methods also require assumptions, which should be described and examined. No such method or sensitivity analysis is reported in the registry record.

The primary endpoint analysis population is not reported. The record does not state whether analysis was based on randomized assignment, treatment received, or another defined population. Nor does it report a statistical analysis plan, interim analyses, or any adjusted analysis. These items should not be inferred from the randomized design or from the endpoint’s planned decision threshold. With zero analyses listed, the registry does not provide enough information to evaluate multiplicity, missing-data handling, or the analysis population.

11. 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: pulmonary embolism (33.3%), syncope (33.3%), fatigue (17.5%), dehydration (17.4%), abdominal pain (16.7%).

The registry lists serious adverse event counts by study group. For the phase II group receiving pemetrexed, cisplatin, and CBP501, 21 participants were affected among 40 at risk; for the phase II pemetrexed-and-cisplatin group, 13 were affected among 23 at risk. For the phase I CBP501 combination group, 5 were affected among 6 at risk. These are registry counts, not a randomized comparison or an adjusted estimate. The phase I group had a dose-finding role and should not be treated as interchangeable with the phase II groups.

The record also lists other adverse event counts: 28 among 40 at risk in the phase II CBP501 group, 15 among 23 at risk in the phase II comparator group, and 6 among 6 at risk in the phase I group. The registry reports deaths of 1, 1, and 4 for those groups, respectively. Death counts and serious adverse event counts are separate entries; the record does not explain their overlap or attribution.

The listed leading serious terms include pulmonary embolism and Syncope at 33.3%, Fatigue at 17.5%, Dehydration at 17.4%, abdominal pain at 16.7%, and deep vein thrombosis at 16.7%. The registry does not identify the group or denominator for each term in this listing. Event definitions, observation periods, relatedness assessments, and comparative safety analyses are not reported, so the figures should be read as descriptive registry entries rather than evidence of a causal treatment difference.

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

The record describes a randomized phase II question: whether adding CBP501 to pemetrexed and cisplatin would be considered for further evaluation based on a planned four-month progression-free survival threshold in previously untreated, unresectable malignant pleural mesothelioma. It also describes an earlier dose-finding phase and lists serious and other adverse event counts. These details explain the study’s intent and some of the information registered about safety.

What the record does not establish is whether the primary threshold was reached, what the observed four-month endpoint rate was, or how the randomized groups compared. There is no reported effect estimate, confidence interval, or test for the primary endpoint. Thus the registered material cannot quantify the magnitude or precision of a treatment difference. The planned decision threshold is not a result, and overall enrollment is not a substitute for phase-specific endpoint data.

The safety entries also do not establish that an event was caused by a study treatment or that one regimen was safer than the other. The serious event counts are descriptive, the phase I group has a different purpose from the randomized phase II groups, and the listed serious terms are not linked to group-specific denominators in the record. Interpretation would require clearer definitions, follow-up information, attribution, and a comparative analysis.

More generally, a completed study designation does not by itself mean that all planned outcomes or analyses are available in the registry. The record supports careful description of the trial design, planned endpoint, and registered event counts. It does not support a claim that either regimen improves outcomes or that either should be selected for an individual patient. The missing primary analysis is central: without it, the efficacy question remains unanswered by the posted registry results.

13. Why This Trial Matters Statistically

This trial is statistically notable because it joins a dose-finding phase to a randomized phase while addressing a specific fixed-time endpoint. The phase I objective was to select a CBP501 dose using dose-limiting toxicities; phase II then evaluated that dose in a defined mesothelioma population. Keeping those objectives distinct is essential. Dose selection and efficacy assessment answer different questions, and the phase I safety experience should not be merged casually with the randomized comparison.

The phase II design includes a randomized comparator and stratification by histology and performance status, features intended to support a structured comparison. Yet a design description is only the framework for inference. The primary endpoint result, analysis population, uncertainty estimate, and treatment contrast are needed to interpret what happened. The registry’s lack of a reported endpoint analysis illustrates why trial registration and trial results are not interchangeable sources of evidence.

The stated threshold also highlights the difference between a planned decision rule and an observed result. A threshold can define what investigators intended to regard as promising enough for further evaluation, but without the observed endpoint count it cannot be applied. Likewise, planning illustrations based on an observed effect are not observed power and cannot replace a reported estimate with uncertainty.

For biostatistical interpretation, this record is a useful reminder to distinguish design features, registered outcomes, and analyzed results. The randomized structure and planned endpoint are informative, but the absence of an analysis limits what can be learned about efficacy, precision, and multiplicity. Descriptive safety entries provide additional context but do not resolve the efficacy question or establish comparative safety.

14. 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 trial-specific limitation of the registry record is that it does not report the primary endpoint results or any analyses. The planned four-month progression-free survival threshold is stated, but the observed number of participants meeting it, the corresponding rate, and any uncertainty estimate are absent. No randomized comparison for the primary endpoint is reported.

The overall enrollment of 69 does not identify the phase II analysis population. The registry does not report phase-specific enrollment, group-specific endpoint denominators, participant disposition, or the number with evaluable four-month status. It also does not describe the outcome assessment schedule or operational criteria for progression. These gaps make it impossible to assess how complete or comparable endpoint ascertainment was across groups.

Important analytic details are also not reported in the registry record: the analysis population, missing-data handling, model or test, adjustment for the stratification factors, multiplicity approach, interim analyses, and statistical analysis plan. No sample-size justification is reported. The available planning description should not be mistaken for the trial’s own design justification or for an analysis result.

The study is open label, and the registry does not state whether progression assessments were blinded or what procedures were used to limit assessment bias. Safety reporting is limited to counts and a list of serious event terms; group-specific denominators for the listed terms, event timing, attribution, and comparative analyses are not given. Finally, the phase I and phase II populations and purposes differ, which limits interpretation of pooled or unqualified safety counts. These limitations reflect gaps in the registry record and do not establish what may have been reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of CBP501 + Pemetrexed + Cisplatin on MPM (Phase I/II) — NCT00700336.
• Registry record last updated 2021-07-20; status last verified 2021-06.
• Results first posted 2021-07-20.
• 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.

18. Record Summary

The registry describes a completed, randomized, open-label, parallel phase I/II study of CBP501 with pemetrexed and cisplatin. Its phase I portion was dose finding in advanced solid tumors; phase II evaluated the combination against pemetrexed and cisplatin in previously untreated, unresectable malignant pleural mesothelioma, with randomization in a 2:1 ratio.

The primary phase II endpoint was the four-month progression-free survival rate in the CBP501 group. The stated plan was to consider the regimen for further evaluation if at least 23 patients, or more than 54%, were free of progression and death at four months. The registry record does not report the observed endpoint result or an analysis comparing groups. It lists serious and other adverse event counts by group, but does not provide a comparative safety analysis or sufficient detail to attribute events. Overall, the record describes the intended question and design but does not provide the primary results needed to answer the efficacy question.