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 as Second-line Therapy in Metastatic Renal Cell Carcinoma (NCT01491672), a na phase 2 study. The primary outcome is Progression-free Survival (PFS) - All Participants.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01491672 |
| Phase | Phase 2 |
| Condition | Metastatic Renal Cell Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 134 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic renal cell carcinoma who had received first-line therapy. The registry record describes three cohorts based on prior treatment: cytokines, sunitinib, or anti-VEGF therapy other than sunitinib. The full analysis set included all enrolled participants.
Intervention
RAD001, described in the study title as everolimus, at 10 mg orally once daily.
Comparator
There was no separate comparison group. The study is recorded as a single-group study with allocation listed as NA and masking listed as none.
Primary question
What was the median progression-free survival during second-line treatment among all participants, as assessed using local radiology review of CT and MRI scans?
The study aimed to evaluate the efficacy and safety of second-line RAD001 in metastatic renal cell carcinoma. Its primary endpoint was progression-free survival (PFS), defined from enrollment until the first documented disease progression or death from any cause. This endpoint describes the time-to-event experience observed in the treated group; without a separate control group, it does not estimate a treatment effect relative to another therapy or to no treatment.
The registry record lists overall survival, clinical benefit rate, objective response rate, duration of response, and PFS duration within each first-line treatment cohort as secondary outcomes. Although the record lists six outcome measures, only these five secondary outcomes are named in the available information. Results for the primary and secondary outcomes are not reported in the registry record.
3. Trial Design
This was an open-label, multicenter phase II study recorded as completed. It enrolled 134 participants and used a single-group model. Allocation is listed as NA, and masking is listed as none. The registry record therefore does not describe a randomized comparison or a blinded treatment assignment.
All participants received RAD001 10 mg orally once daily. The study title identifies the drug as everolimus. Participants were assigned to one of three cohorts based on their first-line therapy: prior cytokines, prior sunitinib, or prior anti-VEGF therapy other than sunitinib. These are prior-treatment cohorts, not separate randomized treatment arms. The registry record does not describe a like-for-like control group.
The full analysis set included all enrolled participants. The primary PFS analysis was based on local radiology review of CT scans and MRI collected until disease progression according to RECIST 1.0. The listed PFS timeframe is 20 months; this is the endpoint timeframe in the record, not a reported median or follow-up estimate.
The study start is listed as 2011-11 and primary completion as 2015-05. Although the record is marked completed, that status does not itself establish that every planned outcome result is available in the registry. Numerical results for the primary endpoint, secondary outcomes, and cohort-specific PFS are not reported in the registry record. The record also does not report a sample-size justification or a detailed statistical 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
| Stage | Prior Sunitinib | Other Prior Vascular Endothelial Growth Factor (VEGF) | Prior Cytokines |
|---|---|---|---|
| STARTED | 58 | 62 | 14 |
| Safety Set | 58 | 61 | 14 |
| COMPLETED | 2 | 2 | 3 |
| NOT COMPLETED | 56 | 60 | 11 |
Reasons for not completing this period:
| Reason | Prior Sunitinib | Other Prior Vascular Endothelial Growth Factor (VEGF) | Prior Cytokines |
|---|---|---|---|
| Lost to Follow-up | 0 | 4 | 1 |
| Withdrawal by Subject | 6 | 7 | 0 |
| Adverse Event | 8 | 10 | 4 |
| Disease progression | 42 | 34 | 6 |
| Protocol deviation | 0 | 1 | 0 |
| Death | 0 | 4 | 0 |
Analysis population for the primary outcome, as defined in the registry: The full analysis set (FAS) was used. It included all enrolled participants.
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 | Prior Sunitinib | Other Prior Vascular Endothelial Growth Factor (VEGF) | Prior Cytokines | Total |
|---|---|---|---|---|---|
| Participants analysed | 58 | 62 | 14 | 134 | |
| Age, Continuous | Years | 56.0 (SD 12.06) | 56.5 (SD 11.14) | 60.3 (SD 10.59) | 56.7 (SD 11.48) |
| Sex: Female, Male: Female | Participants | 15 | 22 | 6 | 43 |
| Sex: Female, Male: Male | Participants | 43 | 40 | 8 | 91 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS) - All Participants, measured over 20 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was median progression-free survival during second-line treatment. PFS was defined as the time from enrollment to the first documented disease progression or death due to any cause. Including death as an event means the endpoint captures either documented progression or death, whichever occurs first under the stated definition.
The endpoint was assessed using local radiology review of CT scans and MRI, with disease progression defined according to RECIST 1.0. The analysis population was the full analysis set, which included all enrolled participants. The registry record lists a timeframe of 20 months.
General: A median time-to-event outcome describes the point by which half of the observed population has experienced the event, subject to the study’s follow-up and censoring procedures. It can provide a compact description of the timing of progression or death. A confidence interval communicates uncertainty around an estimated value; a wider interval generally indicates less precision. The registry record names a 95% confidence interval as the dispersion measure, but does not report the median PFS estimate or its confidence interval. Therefore, the endpoint’s numerical result and its precision are not available in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies median PFS as the primary outcome, but it does not report a numerical median or 95% confidence interval. As a result, the posted information does not establish the observed duration of PFS or how precisely that duration was estimated. The listed 20-month timeframe describes the endpoint’s stated timeframe; it is not itself an outcome value.
The single-group design shapes what can be concluded. The study followed participants receiving RAD001, with cohorts distinguished by prior treatment history. There was no randomized control group in the record. Consequently, the outcome description cannot by itself show how PFS would compare with a different treatment, nor can differences among prior-treatment cohorts be interpreted as effects caused by their prior therapy. Those cohorts may differ in characteristics beyond the treatment history used to define them, and the registry record does not report adjusted comparisons.
The record specifies that PFS was assessed from enrollment to documented progression or death and that local radiology review of CT and MRI was used. This defines the endpoint and assessment approach, but not the outcome result. Numerical results for the named secondary outcomes—including overall survival, response measures, and PFS within each prior-treatment cohort—are not reported in the registry record.
Safety information includes counts of participants affected by serious and other adverse events in the prior-treatment cohorts, as well as several serious-event terms with percentages. These figures describe reported event categories in the registry record. They do not supply a complete account of timing, duration, recurrence, severity beyond the serious-event classification, or causal attribution. The adverse-event entries should therefore be read as descriptive safety reporting, not as a comparison with another treatment.
For time-to-event results, a median and confidence interval would provide complementary information: the median would describe the estimated event timing, while the interval would convey uncertainty. Neither value is available for the primary outcome in the registry record. Without those results and without a comparator, the statistical interpretation is necessarily limited to the study’s design, endpoint definition, and recorded safety counts. No conclusion about comparative benefit or harm can be drawn from the information reported.
9. Statistical Methods Explained
General: PFS is a time-to-event endpoint because the outcome is the time until a defined event, rather than a measurement taken at a single visit. In this study the event was the first documented progression or death from any cause, measured from enrollment. Participants who have not experienced the event by the end of their observed follow-up are typically handled as censored observations in time-to-event analyses. Censoring allows their available follow-up time to contribute information, but interpretation depends on how follow-up and censoring are handled. The registry record does not report the censoring rules, follow-up distribution, or number of events.
What does the median PFS describe?
General: A median time-to-event estimate represents the time at which the estimated event-free proportion reaches one half. It is a summary of the observed time-to-event pattern, not a guarantee about any individual participant’s outcome. The estimate is interpretable alongside its confidence interval, which indicates the statistical uncertainty around it. The registry record specifies median PFS and a 95% confidence interval as the primary outcome summary, but neither numerical value is reported. Accordingly, the observed median and its precision cannot be assessed from the registry information.
What does a single-group design permit?
The study is recorded as single group, with no allocation and no masking. All participants received the same listed intervention, while the cohorts reflect different first-line treatment histories. General: A single-group study can describe outcomes among participants treated under the study conditions. It does not provide a concurrent randomized estimate of what would have happened to similar participants under a different treatment. A comparison between historical subgroups is not equivalent to random assignment, because the groups may differ in ways other than the factor used to classify them. The registry record does not report adjusted cohort comparisons or a causal analysis.
How should the planned sample-size illustrations be understood?
The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns a total number of events using the Schoenfeld approach; other illustrations concern participants per arm. These assumptions describe hypothetical planning calculations, not the design actually recorded for this single-group study. They do not represent observed power, and they do not establish that the study was designed or powered according to those assumptions. The numerical planning illustrations are not reported in the registry record.
General: Planning calculations estimate the sample size or event count needed under specified assumptions. Their results depend on the assumed effect, allocation, significance level, statistical model, and other design choices. A calculation based on an observed effect is retrospective as a planning illustration and should not be read as evidence that the trial had a particular probability of detecting an effect. In this study, the registry record does not give a numerical primary outcome result from which readers could assess the stated effect assumptions.
What is the role of the confidence interval?
General: A confidence interval presents a range of values compatible with the data and the statistical method under repeated sampling. It is not a guarantee that the true value lies within that particular interval, and it does not replace the estimate itself. When a registry record reports both an estimate and interval, readers can consider the magnitude of the estimate and its precision. Here, the record names a 95% confidence interval for median PFS but gives neither its bounds nor the median. Statistical precision therefore cannot be evaluated.
The record states that PFS assessment used local radiology review of CT and MRI, with progression assessed according to RECIST 1.0. This identifies the assessment source and response criteria, but does not describe procedures for resolving disagreement, the schedule of scans, or whether any independent central review occurred. Those details are not reported in the registry record.
The number of analyses listed in the record is zero. This is a registry listing, not evidence that no statistical analyses were performed. The registry record does not provide the analysis outputs needed to reproduce or independently verify the primary endpoint estimate. It also does not report a detailed model specification, missing-data procedures, or multiplicity adjustment. Any such approach should not be inferred from the endpoint type or the phase of the study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists five named secondary outcomes: PFS duration for each first-line treatment cohort, overall survival, clinical benefit rate, objective response rate, and duration of response. It lists six outcome measures in total, but the available information names only those five secondary outcomes. Numerical results for the primary endpoint and the secondary outcomes are not reported in the registry record.
When a study evaluates several outcomes or makes several comparisons, multiplicity can arise: the chance of at least one apparently notable result may increase as more statistical tests are considered. General: Prespecified outcome priorities and adjustment methods can help readers understand how multiple tests were handled. The registry record does not report a multiplicity adjustment or a detailed statistical plan. No adjustment method should be assumed.
The primary analysis population is identified as the full analysis set, including all enrolled participants. That definition identifies who was included in the stated population, but does not establish that every participant had complete endpoint follow-up. The registry record does not report missing-data methods, censoring details, or the extent of missing outcome information. It also does not report how participants without evaluable imaging were handled.
The record lists zero analyses. That entry should not be interpreted as proof that no analyses were conducted; it indicates that analyses are not listed in the registry record. In the absence of reported outcome estimates and analysis details, the completeness and statistical handling of the results cannot be assessed from the registry information.
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 |
|---|---|---|---|
| Prior Sunitinib | 13 | 58 | 22.4% |
| Other Prior Anti VEGF | 16 | 61 | 26.2% |
| Prior Cytokines | 3 | 14 | 21.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Prior Sunitinib | 28 of 58 |
| Other Prior Anti VEGF | 33 of 61 |
| Prior Cytokines | 12 of 14 |
Most frequent serious adverse event terms
| Event term | Organ system | Prior Sunitinib | Other Prior Anti VEGF | Prior Cytokines |
|---|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 58 | 3 of 61 | 0 of 14 |
| Multi-organ failure | General disorders | 1 of 58 | 2 of 61 | 0 of 14 |
| Sepsis | Infections and infestations | 2 of 58 | 1 of 61 | 0 of 14 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 1 of 58 | 2 of 61 | 0 of 14 |
| Anaemia | Blood and lymphatic system disorders | 0 of 58 | 2 of 61 | 0 of 14 |
| Abdominal pain | Gastrointestinal disorders | 2 of 58 | 0 of 61 | 0 of 14 |
| Cellulitis | Infections and infestations | 2 of 58 | 0 of 61 | 0 of 14 |
| Pneumonia | Infections and infestations | 2 of 58 | 0 of 61 | 0 of 14 |
| Hyperglycaemia | Metabolism and nutrition disorders | 1 of 58 | 1 of 61 | 0 of 14 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 58 | 1 of 61 | 0 of 14 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prior Sunitinib | Other Prior Anti VEGF | Prior Cytokines |
|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 8 of 58 | 8 of 61 | 4 of 14 |
| Stomatitis | Gastrointestinal disorders | 5 of 58 | 8 of 61 | 5 of 14 |
| Hyperglycaemia | Metabolism and nutrition disorders | 3 of 58 | 5 of 61 | 1 of 14 |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | 3 of 58 | 4 of 61 | 2 of 14 |
| Pyrexia | General disorders | 2 of 58 | 5 of 61 | 1 of 14 |
| Hypercholesterolaemia | Metabolism and nutrition disorders | 3 of 58 | 3 of 61 | 2 of 14 |
| Diarrhoea | Gastrointestinal disorders | 5 of 58 | 1 of 61 | 0 of 14 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 58 | 4 of 61 | 0 of 14 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 1 of 58 | 4 of 61 | 1 of 14 |
| Mouth ulceration | Gastrointestinal disorders | 2 of 58 | 2 of 61 | 1 of 14 |
Serious events with the highest arm-level rate: cardiac failure (7.1%), lower limb fracture (7.1%), pleural fibrosis (7.1%), respiratory failure (4.9%), abdominal pain (3.4%).
The adverse-event information is organized by prior-treatment cohort. For prior sunitinib, the record lists 58 participants at risk and 13 affected in the serious-event category, and 58 at risk and 28 affected in the other-event category. For other prior anti-VEGF therapy, it lists 61 at risk and 16 affected in the serious-event category, and 61 at risk and 33 affected in the other-event category. For prior cytokines, it lists 14 at risk and 3 affected in the serious-event category, and 14 at risk and 12 affected in the other-event category.
The registry record also lists serious-event terms with percentages: cardiac failure, lower limb fracture, and pleural fibrosis at 7.1% each; respiratory failure at 4.9%; and abdominal pain and cellulitis at 3.4% each. These are descriptive entries, not comparative estimates of risk between treatments.
The record does not report whether participants could experience multiple events, how events were attributed to treatment, or the detailed time period and counting rules for these entries. The figures should be read as recorded safety counts and percentages, not as evidence that an event was caused by RAD001 or that risks differ between cohorts.
12. What the Result Does, and Does Not, Mean
The study record describes a phase II evaluation of RAD001 as second-line therapy in metastatic renal cell carcinoma. It specifies a single-group, open-label design and a primary endpoint of median PFS based on local review of CT and MRI scans. These details clarify what was studied and how the main outcome was defined.
However, the registry record does not report the numerical primary PFS result or its 95% confidence interval. It also does not report numerical results for the listed secondary outcomes. Without the outcome estimates, readers cannot determine the observed PFS duration, the statistical precision of that estimate, or the observed results for survival and response outcomes.
The study has no randomized comparator in the registry record. Its outcomes therefore describe participants who received RAD001, rather than a randomized difference between RAD001 and another treatment. The prior-treatment cohorts are useful descriptive groupings, but they are not treatment arms assigned by randomization. Differences between them cannot establish that prior treatment history caused different outcomes.
The recorded adverse-event counts and percentages describe safety reporting by cohort and event term. They do not establish causation, and they do not provide a comparative estimate against a control group. The record does not provide enough detail to reconstruct event timing, recurrence, or handling of missing safety information.
In statistical terms, the registry information supports an understanding of the study question, design, endpoint definition, analysis population, and some safety counts. It does not support a quantitative conclusion about the primary endpoint, comparative effectiveness, or comparative safety. The absence of reported numerical efficacy results is distinct from a finding of no effect: the registry record does not report a result that would justify either conclusion.
13. Why This Trial Matters Statistically
This study illustrates why design and results must be read together. The record identifies a clear time-to-event primary endpoint and describes the event definition, imaging assessment, and analysis population. Those elements are necessary to understand what a PFS estimate would represent. But without the median and confidence interval, readers cannot assess either the observed event timing or the estimate’s precision.
The single-group design also sets an important interpretive boundary. Outcomes among participants receiving RAD001 can be described, but a treatment contrast requires a suitable comparison. Prior-treatment cohorts do not provide the same protection against confounding as randomized assignment, because they were defined by participants’ treatment histories rather than by random allocation in this study.
The registry record’s sample-size assumptions are explicitly framed as planning illustrations involving hypothetical equal allocation between two arms. This is distinct from the recorded single-group design. Recognizing that distinction prevents a hypothetical calculation from being mistaken for the trial’s own sample-size justification or for observed power.
Finally, the record lists safety counts and named serious-event percentages but does not report detailed event handling or a comparator. Such information can be useful descriptively, yet it cannot on its own establish treatment attribution or relative safety. Together, these features make the record a useful example of how endpoint definitions, uncertainty, design, and completeness of reporting govern the scope of statistical conclusions.
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 central limitation for statistical interpretation is that the registry record does not report the primary median PFS or its 95% confidence interval. Numerical results for the named secondary outcomes are also not reported. The record therefore does not permit assessment of the magnitude or precision of the primary outcome, or comparison of its findings with other treatment approaches.
The single-group, open-label design has no randomized control group. The prior-treatment cohorts are based on treatment history and should not be treated as randomized comparisons. The registry record does not report adjusted comparisons between these cohorts.
Although the PFS definition and local radiology review are described, details such as scan timing, censoring rules, follow-up distribution, and handling of participants without evaluable imaging are not reported in the registry record. The record also does not report missing-data procedures or the detailed statistical plan.
The safety entries provide counts and selected percentages, but the record does not specify event recurrence, attribution, or full counting rules. These omissions limit interpretation of the safety summaries. The record is marked completed, but completion status does not resolve the absence of numerical outcome results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma — NCT01491672.
- Registry record last updated 2016-06-06; status last verified 2016-06.
- Results first posted 2016-06-02.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
This completed, open-label, multicenter phase II study evaluated RAD001 10 mg orally once daily as second-line therapy for metastatic renal cell carcinoma. It enrolled 134 participants in a single-group design, with cohorts defined by prior cytokines, prior sunitinib, or other prior anti-VEGF therapy.
The primary outcome was median PFS, defined from enrollment to documented progression or death and assessed through local review of CT and MRI using RECIST 1.0. The full analysis set included all enrolled participants. The registry record lists a 20-month timeframe but does not report the primary estimate or its 95% confidence interval. Numerical results for the named secondary outcomes are not reported in the registry record.
Safety counts and selected serious-event percentages are listed by cohort. With no randomized comparator and no reported numerical PFS result, the record supports a description of the study design and outcome definitions, but not a quantitative comparative conclusion.