This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity (NCT01024946), a non-randomized phase 2 study. The primary outcome is To Determine the Rate of Clinical Benefit (i.e. Rate of Complete or Partial Response Plus Stable Disease) at 16 Weeks for Patients With Malignant Mesothelioma Treated With Everolimus as Second or Third Line Therapy..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01024946 |
| Phase | Phase 2 |
| Condition | Malignant Pleural Mesothelioma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
The study asked whether everolimus could produce clinical benefit for people with advanced malignant pleural mesothelioma after prior treatment. The registry describes everolimus as second- or third-line therapy and identifies Merlin/NF2 loss as a biomarker to be evaluated for predicting sensitivity. The primary question was whether participants had a complete response, partial response, or stable disease at 16 weeks. The record also describes safety assessment as a study aim.
Population
People with advanced malignant pleural mesothelioma receiving second- or third-line therapy. The title identifies Merlin/NF2 loss as a biomarker of interest. Detailed eligibility criteria and the biomarker-specific enrollment breakdown are not reported in the registry record.
Intervention
Everolimus (RAD001), recorded as a drug intervention. The study description identifies it as the treatment under evaluation. Dose, schedule, and treatment duration are not reported in the registry record.
Comparator
There was no randomized control arm: the allocation is non-randomized and the model is single group. The study therefore does not offer a like-for-like treatment comparison against another intervention or control group.
Primary question
What number of participants had complete response, partial response, or stable disease at 16 weeks, under the registry’s stated endpoint? The endpoint result is not reported in the registry record.
This framing matters because a single-group study can describe outcomes among treated participants but cannot, by itself, separate treatment effects from the course of disease or other influences. The biomarker aim also requires evidence linking biomarker status to outcomes; the registry record does not report such a comparison.
3. Trial Design
The registry classifies this as a phase II, non-randomized, single-group study with no masking. The intervention is everolimus, and the study description characterizes treatment as second- or third-line therapy for advanced malignant pleural mesothelioma. The study is described as multicenter and open label. Enrollment is recorded as 11 participants. The status is completed, with a start date of 2009-12 and primary completion of 2012-07.
A single-group design follows participants receiving the intervention without random allocation to a concurrent comparison group. It can document outcomes and safety observations in the enrolled group. It cannot establish what would have happened to the same participants under another treatment or under a control condition. Non-random allocation also means that the record does not describe a randomized treatment contrast. The registry explicitly cautions that arms are not a like-for-like control comparison.
Open-label means masking was absent in the record. This can matter when outcome assessment involves judgment, because knowledge of treatment may influence how assessments are made or reported. The primary endpoint is described using radiographic response criteria, but the record does not say whether independent or blinded review was used. That assessment procedure is not reported in the registry record.
The overall enrollment is 11, while the adverse-event group lists 7 participants at risk for each of its serious and other event summaries. The registry record does not explain the difference between those counts. It also does not report how many participants completed the 16-week assessment, whether every enrolled participant was included in the primary endpoint analysis, or why any participants might be absent from an analysis. Those details should not be inferred from the enrollment figure.
The record states that the study would evaluate Merlin/NF2 loss as a biomarker to predict sensitivity. It does not report the biomarker assay, how status was determined, or results stratified by biomarker status. Therefore, the design description establishes that biomarker evaluation was an aim, but not whether a predictive relationship was demonstrated.
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
| Stage | Patients Getting Everolimus |
|---|---|
| STARTED | 11 |
| COMPLETED | 6 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Patients Getting Everolimus |
|---|---|
| Screen Failure | 3 |
| Withdrawal by Subject | 1 |
| Adverse Event | 1 |
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.
| Characteristic | Unit | Patients Getting Everolimus |
|---|---|---|
| Participants analysed | 11 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 |
| Age, Categorical: >=65 years | Participants | 4 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as To Determine the Rate of Clinical Benefit (i.e. Rate of Complete or Partial Response Plus Stable Disease) at 16 Weeks for Patients With Malignant Mesothelioma Treated With Everolimus as Second or Third Line Therapy., measured over 16 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with clinical benefit at 16 weeks, defined as complete response, partial response, or stable disease. The registry describes response assessment using RECIST v1.0 for target lesions, assessed by MRI. In that description, complete response means disappearance of all target lesions, while partial response means a decrease of >=30% in the sum of the longest diameter of target lesions. Stable disease is included in the clinical-benefit endpoint, but its operational definition is not reported in the registry record.
Combining response and stable disease gives a broader measure than tumor shrinkage alone: it counts participants whose disease is stable at the assessment point as well as those with a complete or partial response. That can be useful in a study where slowing or preventing further growth is also of interest. It remains a time-specific measure, however. A status at 16 weeks does not, by itself, describe how long that status lasted, whether symptoms changed, or what happened later.
The endpoint title refers to a rate, while the registry lists the measure as a number of participants. No event count or endpoint estimate is reported in the registry record. As a result, the record does not establish how many participants met the definition, nor how precisely the clinical-benefit result was estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and the study population, but it does not report the numerical outcome for clinical benefit at 16 weeks. There is no posted count of participants with complete response, partial response, or stable disease, and no corresponding rate or uncertainty interval. Consequently, the magnitude and precision of the primary result cannot be described from the registry record. The absence of a reported result is not evidence that the endpoint was either met or not met.
The record lists one outcome measure and zero analyses. That tells readers what is represented in this registry entry, but it does not establish that no analysis was conducted outside the record. No estimate, confidence interval, or inferential test for the primary endpoint is reported in the registry record. Without such information, it is not possible to assess whether the observed outcome was compatible with a wide range of underlying outcomes or estimated with greater precision.
The design limits the kind of conclusion that could be drawn even if a group outcome were available. In a single-group study, an outcome among participants receiving everolimus is descriptive of that group. Without a concurrent randomized comparator, it cannot isolate the contribution of everolimus from other influences. The registry also cautions that any non-randomized arms should not be treated as like-for-like control groups. No comparative treatment effect should be inferred from this record.
The biomarker objective requires particular care. The title and study description identify Merlin/NF2 loss as a proposed predictor of sensitivity, but no biomarker-stratified counts, estimates, or analyses are reported in the registry record. A biomarker being named as an aim is not itself evidence that it predicted outcomes. The record does not show whether all participants had the biomarker, whether outcomes differed by status, or whether a formal predictive analysis was performed.
Safety information is reported separately as participant counts and listed serious adverse-event terms. The serious-event group records 7 participants at risk and 3 affected; the other-event group records 7 at risk and 6 affected. Those figures are not a substitute for the missing primary endpoint result. Nor do they establish that an event was caused by everolimus. The registry lists serious-event percentages for selected terms, but does not report a complete context for interpreting them, including event timing or attribution in the information.
Overall, the record supports a description of the study’s purpose, broad design, endpoint definition, and selected safety figures. It does not support a numerical conclusion about clinical benefit, a treatment comparison, or a biomarker effect. These distinctions separate what the registry documents from questions that remain unanswered in the registry record.
9. Statistical Methods Explained
What does a single-group design estimate?
In general, a single-group study describes outcomes among the people enrolled and treated. A count or proportion at a specified assessment can summarize what happened in that group, subject to who was assessed and how outcomes were measured. It does not directly estimate a contrast with an untreated or differently treated group. Such a contrast requires a suitable comparator and an analysis that addresses how the groups were formed. In this study, the registry identifies a single-group model and non-random allocation, so there is no randomized control comparison to interpret.
Randomization is used in general to make treatment groups comparable in expectation, reducing the chance that baseline differences systematically favor one group. It does not guarantee identical groups, especially in small studies, but it provides a basis for interpreting between-group contrasts. When randomization is absent and no suitable comparator is recorded, differences between groups can reflect patient selection, disease characteristics, care, or other factors as well as treatment. The registry itself cautions against treating non-randomized arms as like-for-like controls.
How should a binary endpoint be read?
General explanation: a binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a defined event criterion. A count describes the number meeting the criterion; a proportion relates that count to the number assessed. The denominator matters. If some enrolled participants have no assessment, an analysis can depend on whether they are included, excluded, or handled under a stated missing-data rule. The registry does not report the primary endpoint count, denominator, analysis population, or missing-data rule, so those elements cannot be reconstructed.
The clinical-benefit definition groups complete response, partial response, and stable disease at 16 weeks. This makes the endpoint a snapshot at a fixed assessment time. General explanation: fixed-time endpoints can be straightforward to communicate, but they do not capture the full timing or duration of events. Participants assessed at different times, or participants without an assessment at the target time, require clearly specified handling. That handling is not reported in the registry record.
What does a confidence interval contribute?
General explanation: a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, while neither width alone nor the interval’s position establishes causality. For a single-group endpoint, an interval around a proportion would describe uncertainty in the group estimate; it would not create a treatment comparison that the design does not provide. No confidence interval for the primary endpoint is reported in the registry record, so precision cannot be evaluated.
A significance test, when used, addresses a specified statistical hypothesis under a model and assumptions. A p-value does not measure the size or clinical importance of an effect, and it does not resolve design limitations. The record lists zero analyses and does not report a p-value or a statistical testing plan. Thus no test result or inferential conclusion can be described.
Why do assessment procedures matter?
General explanation: an endpoint is interpretable only to the extent that its measurement rule is clear and applied consistently. RECIST v1.0 provides the stated framework for evaluating target lesions, and the record says assessment was by MRI. The definitions recorded for complete and partial response make parts of the endpoint explicit. Stable disease is included, but its definition is not reported in the registry record. The record also does not say whether assessors were independent, whether imaging review was blinded, or how disagreements were resolved. Those details can affect the reproducibility of a radiographic endpoint, but they cannot be assumed.
How should sample-size planning be distinguished from results?
General explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event frequency, significance level, power, and design. A planning number is not an observed outcome and is not evidence that a study had a particular probability of finding a result after it was conducted. The planning illustrations described for the site use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of an observed effect. They are described as illustrations rather than the trial’s own design. Equal allocation between two arms does not describe this study’s recorded single-group design.
General explanation: over-dispersion occurs when outcome variability is greater than a simple statistical model assumes. If present, it can make standard errors too small and confidence intervals too narrow unless the analysis accounts for it. The primary endpoint is recorded as a participant count, and dispersion is not specified. The registry does not report a model or variance estimate for the endpoint, so over-dispersion cannot be assessed as an analysis feature in this study.
Finally, a statistical method is only as interpretable as its assumptions and analysis population. The record does not report the protocol’s statistical plan, sample-size justification, interim analyses, endpoint analysis method, or analysis population. Those details are not reported in the registry record and should not be inferred from the phase designation or enrollment count.
10. Multiplicity, Missing Data and Analysis Populations
The registry records one outcome measure and zero analyses. It identifies the clinical-benefit endpoint as primary, but does not provide a statistical analysis plan or describe how multiple outcomes, repeated assessments, or subgroup analyses were handled. A multiplicity strategy is not reported in the registry record.
General explanation: when several outcomes, time points, or subgroup comparisons are tested, the chance of at least one apparently notable result can increase if each is treated as an isolated test. Prespecified prioritization and adjustment methods can help manage that issue. Their use cannot be assumed. The record’s biomarker objective makes subgroup questions relevant, but it does not report whether a biomarker analysis was prespecified, how many comparisons were planned, or whether any adjustment was used.
Missing-data handling is also not described. The record does not state how participants without a 16-week assessment were treated, whether assessments were available for every enrolled participant, or whether sensitivity analyses were performed. These are important details for a fixed-time endpoint because the number assessed can differ from the number enrolled. Enrollment is 11, while the adverse-event groups list 7 at risk; the record does not explain that distinction, and it should not be used to infer the primary endpoint denominator.
The analysis population is not reported in the registry record. It is therefore not possible to determine whether the endpoint was evaluated among all enrolled participants, participants who received treatment, participants with an assessment, or another defined group. The record also does not describe interim analyses or stopping rules. None of these omissions establishes that a procedure was absent from the study; they mean the information is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Patients Getting Everolimus | 3 | 7 | 42.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Patients Getting Everolimus | 6 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Patients Getting Everolimus |
|---|---|---|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | 2 of 7 |
| Constipation | Gastrointestinal disorders | 1 of 7 |
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | 1 of 7 |
| Inf norm ANC/gr1/2 neut-Myositis infection(muscle) | Musculoskeletal and connective tissue disorders | 1 of 7 |
| Inf norm ANC/gr1/2 neut-Cellulitis(skin) | Skin and subcutaneous tissue disorders | 1 of 7 |
| Hemorrhage/Bleeding, other | Blood and lymphatic system disorders | 1 of 7 |
| Ascites (non-malignant) | Respiratory, thoracic and mediastinal disorders | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patients Getting Everolimus |
|---|---|---|
| Albumin, low (hypoalbuminemia) | Metabolism and nutrition disorders | 4 of 7 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 7 |
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | 4 of 7 |
| Fatigue (asthenia, lethargy, malaise) | General disorders | 4 of 7 |
| Glucose, high (hyperglycemia) | Blood and lymphatic system disorders | 4 of 7 |
| Hemoglobin | Blood and lymphatic system disorders | 2 of 7 |
| Leukocytes (total WBC) | Blood and lymphatic system disorders | 2 of 7 |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | 2 of 7 |
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | 2 of 7 |
| ALT, SGPT | Metabolism and nutrition disorders | 1 of 7 |
Serious events with the highest arm-level rate: dyspnea (shortness of breath) (28.6%), constipation (14.3%), pneumonitis/pulmonary infiltrates (14.3%), inf norm anc/gr1/2 neut-myositis infection(muscle) (14.3%), inf norm anc/gr1/2 neut-cellulitis(skin) (14.3%).
The registry lists a serious adverse-event group titled “Patients Getting Everolimus,” with 7 participants at risk and 3 affected. The other adverse-event group lists 7 participants at risk and 6 affected. These are separate group summaries; the record does not explain why the number at risk differs from overall enrollment of 11. It also does not establish that every event was caused by everolimus.
The serious-event terms and percentages listed include Dyspnea (shortness of breath), 28.6%; Constipation, 14.3%; Pneumonitis/pulmonary infiltrates, 14.3%; Inf norm ANC/gr1/2 neut-Myositis infection(muscle), 14.3%; Inf norm ANC/gr1/2 neut-Cellulitis(skin), 14.3%; and Hemorrhage/Bleeding, other, 14.3%. These are registry-listed figures for selected terms, not a complete description of each participant’s clinical course. The record does not provide event timing, duration, severity detail beyond the serious-event classification, or attribution for each event in the information available.
General explanation: adverse-event percentages describe recorded events within a stated reporting context; interpretation depends on the denominator, event definitions, collection period, and whether events were counted by participant or occurrence. A percentage does not alone establish causation or allow comparison with a different study. Deaths are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The result that can be drawn from this registry entry is limited. It documents a completed phase II study of everolimus in a single group, a primary endpoint focused on clinical benefit at 16 weeks, and selected adverse-event summaries. The numerical clinical-benefit outcome itself is not reported in the registry record. Therefore, the entry does not show the number of participants who met the endpoint or the precision of an estimate.
Even if the clinical-benefit count were available, a single-group outcome would describe the enrolled participants rather than establish the effect of treatment compared with an alternative. The absence of randomized allocation means that changes or outcomes cannot be attributed to everolimus by a direct randomized contrast. The record also does not report a comparative analysis that would support a treatment-effect estimate.
The biomarker language should likewise be read as an objective, not as a finding. The title identifies Merlin/NF2 loss as a candidate biomarker for sensitivity, but the registry record does not report biomarker status by participant, outcome results by status, or a test of whether the biomarker predicted response. No claim about predictive performance follows from the stated aim alone.
The endpoint is a point-in-time composite of complete response, partial response, and stable disease. It is not, by itself, a measure of how long benefit lasted, symptoms, quality of life, or outcomes after the assessment. Those outcomes are not reported in the registry record. The study description says safety was also studied, and selected adverse-event figures are listed, but those figures do not answer the missing efficacy question or establish treatment causation.
In general, interpreting a clinical result requires both an estimate and information about its uncertainty, measurement, analysis population, and study design. The registry entry does not report several of these elements for the primary outcome. The most accurate reading is therefore that the registry documents the study question and design but does not provide enough primary-endpoint results to quantify clinical benefit or assess its precision.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a small recorded enrollment with an objective that includes both radiographic response and stable disease. Enrollment is 11, and the primary endpoint is a fixed-time clinical-benefit measure at 16 weeks. Such an endpoint can be clinically interpretable as a status at a defined assessment, but its numerical value and denominator are essential for understanding what occurred. Neither is reported for the primary endpoint in the registry record.
The single-group design is also central to interpretation. It can describe outcomes among participants receiving everolimus, but a treatment effect requires a contrast that the recorded design does not supply. This distinction is especially important when a study is intended to evaluate a biomarker: demonstrating that a marker predicts sensitivity generally requires outcomes to be related to biomarker status in an analysis that can distinguish prediction from other differences. No such results are reported in the registry record.
The case also illustrates why outcome definitions and analysis details matter. RECIST v1.0 and MRI are named, and the record describes complete and partial response. Stable disease is part of the composite but is not further defined in the registry entry. The analysis population, missing-data rules, confidence interval, and statistical plan are also not reported. Without those details, readers cannot assess endpoint completeness or precision.
Finally, selected safety summaries should be kept distinct from efficacy interpretation. The registry gives counts for participants at risk and affected, along with selected serious-event terms and percentages, but does not report event attribution or the context needed to compare these figures across studies. Overall, the statistical importance lies in the difference between the intended question and the results documented: the study aim is clear, while the primary outcome and biomarker findings are not reported in the registry record.
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 main limitation for interpretation is that no numerical result for the primary clinical-benefit endpoint is reported in the registry record. Without the event count, denominator, or an uncertainty estimate, the endpoint’s magnitude and precision cannot be evaluated. The registry lists one outcome measure and zero analyses, but does not provide an endpoint analysis or its statistical method.
The recorded design is non-randomized and single group, with no masking. There is no concurrent randomized comparison from which to estimate a treatment contrast. The registry cautions that arms are not a like-for-like control comparison. The open-label design may also matter for assessment, but the record does not say whether imaging was independently or blindly reviewed.
Enrollment is recorded as 11, whereas the adverse-event groups list 7 participants at risk. The registry does not explain this difference. It does not identify the primary endpoint analysis population or say how many participants had the 16-week assessment. Missing-data rules, reasons for missing assessment, and sensitivity analyses are not reported in the registry record.
The biomarker objective is not accompanied by biomarker-specific results. The assay, classification method, participant status, subgroup outcomes, and predictive analysis are not reported. The endpoint definition includes stable disease, but its operational criteria are not stated. Dose, schedule, and treatment duration are also not reported in the registry record.
Safety interpretation is limited to the listed counts and selected serious-event terms and percentages. Event timing, attribution, and broader context are not reported, and deaths are not reported in the registry record. These limitations identify gaps in the available registry information; they do not establish that the omitted procedures or data were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Everolimus (RAD001) for the Treatment of Malignant Pleural Mesothelioma With Merlin/NF2 Loss as a Biomarker to Predict Sensitivity — NCT01024946.
- Registry record last updated 2015-05-12; status last verified 2015-04.
- Results first posted 2015-04-20.
- 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.
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18. Record Summary
The registry describes NCT01024946 as a completed phase II, open-label, non-randomized, single-group study of everolimus for advanced malignant pleural mesothelioma. It records enrollment of 11, a start date of 2009-12, and primary completion of 2012-07. The study description identifies second- or third-line treatment and evaluation of Merlin/NF2 loss as a potential biomarker of sensitivity.
The primary endpoint is the number of participants with complete response, partial response, or stable disease at 16 weeks, assessed using RECIST v1.0 criteria and MRI. The endpoint result, analysis population, missing-data procedures, statistical plan, and biomarker-specific results are not reported in the registry record.
Adverse-event summaries list 7 participants at risk and 3 affected for serious events, and 7 at risk and 6 affected for other events. Selected serious-event terms and percentages are recorded; deaths are not reported in the registry record. The available entry describes the study question and design but does not provide a numerical primary-outcome result or a randomized treatment comparison.