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 Study of Everolimus (RAD001) in Combination With Lenalidomide (NCT01218555), a na phase 1 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01218555 |
| Phase | Phase 1 |
| Condition | Solid Organ Malignancies, Adenoidcystic Carcinoma, Neuroendocrine Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 44 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Emory University |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with advanced solid malignancies. The official title describes a population enriched for renal cell carcinoma, while the listed conditions include solid organ malignancies, adenoidcystic carcinoma, and neuroendocrine tumors. The brief summary describes people whose cancer was no longer responding to standard treatment or who could not tolerate standard treatment. The registry record does not report further eligibility details or the numbers enrolled within each cancer type.
Intervention
The intervention was the combination of everolimus and lenalidomide, both listed as drugs. Lenalidomide was given orally each day at escalating doses, alongside standard doses of orally administered everolimus. The record describes five planned dose cohorts, beginning with lenalidomide 10 mg and everolimus 5mg in a 28-day cycle, with maximum doses of 25 and 10 mg, respectively. It does not report the actual dose received by each participant.
Comparator
There was no separate comparison group: the study is listed as single-group and non-randomized, with no masking. The registry therefore does not describe a randomized comparison of the combination against either drug alone, standard care, or placebo. Results should be read as observations from participants in the combination study, not as estimates of a difference between treatment groups.
Primary question
The primary outcome concerns the number of participants with dose-limiting toxicities at each dose level. The record says these toxicities were assessed within the first 28 days, while safety was assessed throughout the study. The described 3 + 3 dose-escalation rules governed whether escalation could proceed. The record does not report the number with dose-limiting toxicities in any cohort, so the primary question cannot be answered from the posted outcome information.
3. Trial Design
This was a phase I, completed, single-group study sponsored by Emory University. The registry lists an enrollment of 44 and describes a non-randomized dose-escalation design. Masking was listed as none. There was no parallel control arm, so the study was not designed as a like-for-like comparison of the combination with another treatment.
The combination paired daily oral lenalidomide at escalating doses with standard-dose oral everolimus. The record describes five planned cohorts. The starting regimen was lenalidomide 10 mg with everolimus 5mg in a 28-day cycle, and the stated maximum doses were 25 and 10 mg, respectively. These are descriptions of the plan; the registry record does not identify how many participants received each dose or whether every planned cohort was opened.
The record describes a standard 3 + 3 design. Escalation to the next cohort required 0 of 3 or no more than 1 of 6 patients with a dose-limiting toxicity. This identifies the decision rule in the registry description, but not the observed toxicity counts or the dose-escalation decisions made during the trial.
The listed start date is 2010-09-09 and the primary completion date is 2020-11-05. The status is completed. These dates describe the registry timeline; they do not establish when individual participants were treated or how long each person was followed. Individual treatment duration and cohort-specific enrollment 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
| Stage | Dose Level 1 Lenalidomide/Everolimus 10/5 mg | Dose Level 2 Lenalidomide/Everolimus | Dose Level 3: Lenalidomide/Everolimus | Dose Level 4: Lenalidomide/Everolimus 20/5/mg | Dose Level 5: Lenalidomide/Everolimus (25/10mg) | RP2D: L (25mg) and E (10mg) |
|---|---|---|---|---|---|---|
| STARTED | 3 | 3 | 5 | 3 | 8 | 22 |
| COMPLETED | 3 | 3 | 5 | 3 | 8 | 22 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
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 | Lenalidomide Combination With Everolimus |
|---|---|---|
| Participants analysed | 44 | |
| Age, Continuous | Years | 58 (SD 44) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 28 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 40 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 |
| Race (NIH/OMB): White | Participants | 32 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 44 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLT) at Each Dose Level, measured over Within the first 28 days for DLT and throughout the duration of the study for safety..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with dose-limiting toxicities at each dose level. The record defines the relevant DLT observation period as the first 28 days; safety monitoring is described as continuing throughout the study. It does not give a specific list of qualifying toxicities or a detailed rule for classifying an event as dose-limiting.
In general, early-phase dose-escalation studies use dose-limiting toxicity counts to guide decisions about whether it is acceptable to move to a higher dose cohort. The 3 + 3 rule described in this registry links those counts to escalation: the next cohort could be entered if 0 of 3 or no more than 1 of 6 patients experienced a DLT. That rule explains the role of the endpoint in the design; it does not itself reveal which dose was selected or how many DLTs occurred.
The outcome is a count of participants, rather than a continuous measurement such as a laboratory value. The registry names the measure and its observation period but does not post the count for any dose level. Consequently, the endpoint's observed distribution, and the dose-specific safety results it was intended to inform, are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that 44 participants were enrolled in a completed phase I study of everolimus with escalating doses of lenalidomide. It also specifies the intended primary measure: participants with dose-limiting toxicities at each dose level. However, the registry lists zero analyses and does not report dose-level DLT counts. Enrollment alone cannot answer the primary question. Without those counts, readers cannot determine from the posted outcome information how many DLTs occurred, how those events were distributed across cohorts, or how the stated escalation rule was applied.
The design is single-group and non-randomized. Its observations therefore describe participants treated with the combination rather than a treatment contrast against a control group. There is no randomized estimate of what would have happened under another treatment or under no study treatment. The record also does not report a comparison with either component drug alone.
The adverse-event summary lists 18 participants at risk for serious adverse events and 18 affected, among 44 at risk. For other adverse events, it lists 38 affected among 44 at risk. It separately lists 18 deaths and identifies All-Cause Mortality at 40.9% among the top serious terms. These figures are descriptive registry summaries. They do not establish whether an event was caused by the study drugs, and the record does not give event timing, dose, individual clinical context, or a comparator rate. The relationship between the serious-event, other-event, and death counts is not explained; they should not be combined or treated as mutually exclusive categories.
Precision cannot be assessed for the primary endpoint because dose-specific counts and uncertainty estimates are not reported. The registry contains no primary analysis estimates or confidence intervals. The adverse-event counts likewise do not include reported uncertainty intervals. The record's overall enrollment is not a substitute for the number assessed at each dose or the number contributing to each outcome.
Any planning illustration based on an observed effect should be distinguished from the trial's actual design and results. The record describes equal allocation between two arms as an assumption for such illustrations, whereas this study is listed as a single group. An illustration using that assumption is not an observed power calculation and does not make this trial a two-arm study. The registry record does not report a trial-specific sample-size justification.
9. Statistical Methods Explained
Statistical interpretation begins with the design. This was a single-group, non-randomized phase I study, with no masking. Participants entered escalating dose cohorts for a combination of lenalidomide and everolimus. Because there is no randomized comparator, the design supports description of outcomes among participants in the study, not a randomized estimate of a treatment difference. General statistical principle: randomization helps balance known and unknown prognostic factors between groups; without a randomized comparison, differences from an external population may reflect differences in participants, care, or observation as well as treatment.
What does the 3 + 3 rule do?
The registry describes a 3 + 3 dose-escalation rule. In general, such a rule uses the number of participants with dose-limiting toxicity in a cohort to decide whether escalation may proceed. Here, the stated condition for moving to the next cohort was 0 of 3 or no more than 1 of 6 patients with DLT. This describes a decision rule, not an observed result. The actual DLT counts, cohort sizes, escalation decisions, and selected dose are not reported in the registry record.
The primary outcome is a count of participants with a DLT at each dose level, with DLT assessed within the first 28 days. A count answers how many participants met the outcome definition; it is not the same as a complete account of how often events occurred or how severe they were. General statistical principle: a count can be interpreted alongside the number assessed in the relevant group, and an estimated proportion can describe the frequency within that group. No such dose-specific denominators or proportions are posted for this primary endpoint, so no dose-specific frequency can be read from the record.
How should uncertainty be understood?
General statistical explanation: a confidence interval describes a range of values compatible with the data and the method used to calculate it. It helps show the precision of an estimate; a wide interval generally indicates less precision than a narrow interval. The registry record does not report a primary endpoint estimate or a confidence interval, so the precision of the DLT results cannot be evaluated. The adverse-event summary provides counts and a listed percentage for a serious-event term, but no confidence intervals.
General statistical explanation: for outcomes expressed as counts or proportions, the amount of information depends not only on the total number enrolled but also on how many participants were assessed in the relevant group and whether observations are complete. The record's enrollment of 44 does not show how participants were distributed among the planned dose cohorts, nor does it establish the denominator used for each primary endpoint analysis. Those details are not reported in the registry record.
What do the planning assumptions mean?
The record describes sample-size planning illustrations based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. These are assumptions for planning illustrations, not a description of this trial's single-group dose-escalation design. The record does not report a trial-specific sample-size justification or an observed-power analysis. A planning calculation estimates what sample size might be needed under specified assumptions; it does not change the actual design or demonstrate that an effect was detected.
General statistical explanation: power is a design property calculated under assumptions about the effect, variability, significance threshold, and analysis. It is not a measure of how likely the observed result is to be true. An observed-power calculation using an estimated effect does not add evidence beyond the estimate and its uncertainty. Any sample-size figure based on a hypothetical effect should therefore be read as a planning illustration, not as an outcome of this trial.
What can be concluded from the posted analyses?
The registry lists one outcome measure and zero analyses. The named primary outcome is clear, but the record does not provide its observed results. There are consequently no reported model estimates, adjusted comparisons, or hypothesis-test results to interpret. General statistical principle: statistical significance, when reported, does not by itself convey the size or clinical importance of an effect; estimates and their uncertainty are needed for that assessment. In this record, the missing primary results prevent either kind of assessment.
The adverse-event summary should be interpreted separately from the primary endpoint. It lists numbers of participants with serious and other adverse events, plus a death count and a serious-event term percentage. These summaries do not state a causal comparison or provide dose-specific rates. General statistical principle: safety summaries are most informative when their event definitions, follow-up periods, denominators, and relationship to treatment are clear. Several of those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure, the count of participants with dose-limiting toxicities at each dose level, and zero analyses. It does not report a multiplicity adjustment or a hierarchy for testing outcomes. With no posted primary endpoint analysis, there are no reported tests whose multiplicity handling can be evaluated. The listed measure and the described dose-escalation decision rule should not be mistaken for a complete statistical analysis plan.
Missing-data methods are not reported in the registry record. It does not state how participants who did not complete the first 28 days, had incomplete toxicity assessments, or otherwise lacked outcome information were handled. The record also does not report whether any primary endpoint observations were missing. Without these details, the number enrolled cannot be assumed to equal the number evaluable for DLT.
Analysis populations are not reported in the registry record. It does not specify whether the primary outcome used all enrolled participants, participants who received study treatment, or a defined evaluable cohort. Dose-level denominators and participant flow are also not reported. These omissions matter because the count of participants with DLT is interpretable only in relation to the group assessed and the rules for including participants.
For safety, the record gives 44 at risk for serious and other adverse events, but does not describe how the at-risk population was defined, whether follow-up differed among participants, or how incomplete safety reporting was handled. It also does not explain whether the serious-event, other-event, and death summaries overlap. These limitations prevent reconstruction of a more detailed analysis from 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 |
|---|---|---|---|
| Lenalidomide Combination With Everolimus | 18 | 44 | 40.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lenalidomide Combination With Everolimus | 18 of 44 |
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 |
|---|---|
| Lenalidomide Combination With Everolimus | 38 of 44 |
Most frequent serious adverse event terms
| Event term | Organ system | Lenalidomide Combination With Everolimus |
|---|---|---|
| All-Cause Mortality | General disorders | 18 of 44 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lenalidomide Combination With Everolimus |
|---|---|---|
| Fatigue | General disorders | 15 of 44 |
| Diarrhea | Gastrointestinal disorders | 13 of 44 |
| Anorexia | Gastrointestinal disorders | 11 of 44 |
| Nausea | Gastrointestinal disorders | 11 of 44 |
| Rash | Skin and subcutaneous tissue disorders | 9 of 44 |
| ALT | Metabolism and nutrition disorders | 7 of 44 |
| Elevated AST | Metabolism and nutrition disorders | 5 of 44 |
Serious events with the highest arm-level rate: all-cause mortality (40.9%).
The registry lists 44 participants at risk for serious adverse events, with 18 affected. For other adverse events, it lists 44 at risk and 38 affected. It separately reports 18 deaths. The top serious-event term is All-Cause Mortality, listed at 40.9%. These are descriptive registry figures, not a randomized comparison or a causal estimate.
The record does not define the relationship between the serious and other adverse-event categories, so their affected counts should not be added together. It also does not explain how the death count relates to the serious-event term listing or whether every death was considered treatment-related. The label All-Cause Mortality describes deaths from any cause; it does not attribute them to the study drugs.
Interpretation is limited by the absence of event timing, dose-level safety results, individual event descriptions, and a comparator group. The record describes safety monitoring throughout the study, but does not give participant-specific follow-up or further detail about ascertainment. The counts therefore communicate what the registry summarizes, but not why events occurred or how the figures compare with outcomes under another treatment.
12. What the Result Does, and Does Not, Mean
The registry record documents a completed phase I study of everolimus with escalating doses of lenalidomide in people with advanced solid malignancies. It describes the planned dose cohorts, the 3 + 3 escalation rule, the primary DLT outcome, and summary adverse-event figures. It also reports an enrollment of 44. These details characterize the study's design and registry summaries.
The primary endpoint results are not reported by dose level. As a result, the record does not establish how many participants experienced a DLT, which dose levels were evaluated in practice, or what dose-escalation decisions followed. It also does not report a primary analysis estimate or its precision. The endpoint was intended to inform dose escalation, but the posted record does not provide the outcome data needed to interpret that question.
The adverse-event figures describe counts in the study group and include a listed All-Cause Mortality percentage. They do not establish that everolimus, lenalidomide, or their combination caused an event. Because the study has no control group, the registry does not support a randomized comparison of safety or outcomes against another treatment. It also does not report detailed follow-up or dose-specific safety results.
In general, a phase I dose-escalation study addresses early questions about safety and dose selection rather than establishing comparative treatment benefit. That general context does not fill in missing results for this particular study. The registry record should be read as a description of the design and reported safety summaries, not as evidence for an unreported primary endpoint result or an estimate of comparative efficacy.
13. Why This Trial Matters Statistically
This trial is statistically notable for the contrast between a clearly described dose-escalation rule and the absence of posted primary endpoint counts. The registry explains how DLT observations were intended to guide escalation, but does not report the cohort-specific observations required to see how the rule operated. This illustrates why a protocol description and an outcome result answer different questions: the first states what investigators planned to do, while the second reports what was observed.
The single-group design also defines the limits of interpretation. It can describe participants treated in the study, but it cannot provide a randomized comparison with a control group. This is important when reading safety summaries, since counts without a comparator do not show whether outcomes were more or less common than they would have been under another treatment or in another population.
The record further highlights the distinction between enrollment and evaluability. Although 44 participants were enrolled, the registry does not report dose-level enrollment, analysis populations, or missing-data handling for the primary endpoint. Total enrollment alone cannot establish the amount of information available for each dose-specific estimate.
Finally, planning illustrations based on two-arm allocation assumptions should not be conflated with this single-group study. General statistical practice distinguishes a hypothetical sample-size calculation from observed results and from a trial's actual design. Keeping those concepts separate helps prevent planning assumptions from being read as evidence that the primary endpoint was analyzed or that an effect was demonstrated.
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 most important trial-specific limitation in the registry record is the absence of primary endpoint results. Although the outcome is defined as the number of participants with DLT at each dose level, no dose-specific counts, denominators, or analysis estimates are reported. The registry lists zero analyses. It is therefore not possible to assess the observed DLT pattern or the precision of any dose-specific result.
The record describes five planned dose cohorts but does not identify which cohorts were actually opened, how many participants entered each cohort, or what doses participants received. It gives an escalation rule but not the decisions made under that rule. A planned regimen should not be treated as proof that every cohort or dose was studied.
The single-group, non-randomized design has no control arm and no masking. Consequently, the registry does not offer a direct randomized comparison, and the adverse-event summaries cannot be interpreted as comparative risks. The record also does not report detailed eligibility criteria, participant characteristics by cancer type, dose-specific safety results, or individual follow-up.
Further limitations include unreported analysis populations, missing-data methods, and the relationship among the serious-event, other-event, and death summaries. Although the record lists 44 participants at risk for adverse events, it does not explain the at-risk definition or provide event timing. It also does not report a trial-specific sample-size justification. These omissions constrain interpretation of both the intended dose-escalation endpoint and the posted safety figures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Everolimus (RAD001) in Combination With Lenalidomide — NCT01218555.
- Registry record last updated 2022-01-27; status last verified 2021-11.
- Results first posted 2022-01-27.
- 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
NCT01218555 is a completed phase I, single-group study sponsored by Emory University. It evaluated daily oral lenalidomide at escalating doses in combination with oral everolimus in patients with advanced solid malignancies. The registry lists enrollment of 44, a start date of 2010-09-09, and a primary completion date of 2020-11-05.
The primary outcome was the number of participants with dose-limiting toxicities at each dose level, assessed within the first 28 days; safety was assessed throughout the study. The record describes five planned cohorts and a 3 + 3 escalation rule. It does not report the primary endpoint counts or analyses. The adverse-event summary lists 18 participants affected by serious events, 38 affected by other events, 18 deaths, and All-Cause Mortality at 40.9%. The study had no randomized comparator, and the registry does not establish that reported events were caused by treatment.