LEE011 Plus Everolimus in Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for LEE011 Plus Everolimus in Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy (NCT02985125), a non-randomized phase 1, phase 2 study. The primary outcome is Phase I: Determine the Recommended Phase II Dose (RP2D).

2. Clinical Question

The study concerns dose selection, not a direct test of the combination against another treatment. Its Phase II outcomes include progression-free survival, overall survival, best response using RECIST v1.1 criteria, and adverse events assessed by NCI CTCAE v4.03. These outcomes could describe disease course, response, and safety, but their results are not reported in the registry record. Without a concurrent comparator, outcomes observed in this single-group study would not by themselves establish how the combination compares with another treatment or with no treatment.

3. Trial Design

This is a Phase I/II study listed as completed, with enrollment of 12. The record describes it as single-arm, open-label, and multi-institutional. Allocation is non-randomized, masking is absent, and the study model is single-group. The listed start date is 2017-05-04 and the primary completion date is 2019-07-24.

The Phase I descriptions include LEE011 dose levels of 150mg, 200mg, 250mg, and 300mg, each taken orally once daily on days 1-21 of 28-day cycles. Everolimus is listed as 2.5mg orally once daily on days 1-28. The Phase II description specifies the recommended Phase II dose of LEE011 once daily on days 1-21, with everolimus 2.5mg once daily on days 1-28. The record does not state which dose was ultimately recommended.

The stated primary objective is to determine the recommended Phase II dose from dose-limiting toxicities during the first 4 weeks. The Phase II outcomes listed are progression-free survival, overall survival, best response by RECIST v1.1 criteria, and adverse events by NCI CTCAE v4.03. The registry record does not report results for these outcomes. It also does not describe the dose-escalation or dose-selection rules, the number assigned to each dose level, or the treatment duration for each participant. As the study was not randomized and had no separate control group, differences between dose-level groups should not be interpreted as controlled treatment effects.

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

Analysis population for the primary outcome, as defined in the registry: All dose levels used to determin the recommended dose

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 Phase I: Determine the Recommended Phase II Dose (RP2D), measured over First 4 weeks of treatment.

The primary endpoint is to determine the recommended Phase II dose of LEE011, in combination with everolimus, for participants with metastatic pancreatic adenocarcinoma refractory to 5-FU- and GEM-based chemotherapy. The registry defines the assessment window as the first 4 weeks of treatment and says the dose decision is based on dose-limiting toxicities during that period. The endpoint is expressed in mg.

Dose-finding endpoints serve a different purpose from efficacy endpoints. They are used to guide the choice of a dose for later study, using tolerability information gathered under the specified assessment window. The Phase I descriptions list different LEE011 dose levels while keeping everolimus at 2.5mg. The registry record does not report the observed dose-limiting toxicities, the rule used to classify them, or the recommended Phase II dose. It therefore does not establish from the posted primary endpoint whether any particular dose was selected.

The listed Phase II measures address other questions, including progression-free survival, overall survival, best response, and adverse events. Those are not substitutes for the primary dose-selection outcome. Results for them are not reported in the registry record, so no conclusions about their observed values or precision can be drawn from this entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described from the registry are limited to the design, primary objective, outcome labels, and stated assessment windows or instruments. The record identifies a Phase I/II, single-group, non-randomized, open-label study. It does not report a detailed statistical analysis plan, so methods beyond those explicit descriptions cannot be established from the registry record.

What does the primary endpoint measure?

The primary endpoint is a dose-selection objective: determine the recommended Phase II dose of LEE011 with everolimus using dose-limiting toxicities in the first 4 weeks. It is not a measure of tumor response or survival. Dose-limiting toxicity is the stated basis for the decision, but the registry does not provide the operational definition, grading threshold, attribution rules, or decision algorithm. Those details matter because different definitions or rules can produce different dose recommendations.

What do the Phase II outcomes describe?

Progression-free survival concerns time until disease progression or death under a specified analysis definition; overall survival concerns time until death. These are general descriptions of the outcome concepts. The registry lists both outcomes but does not report their analysis definitions, event counts, estimates, follow-up duration, or censoring rules. Best response is listed using RECIST v1.1 criteria, and adverse events are listed as assessed by NCI CTCAE v4.03. The registry record does not provide the response results or detailed safety analysis methods for these Phase II outcomes.

Why does the design matter?

In a randomized comparison, random assignment is intended to make groups comparable on average, supporting an estimate of the difference between assigned strategies. This study is explicitly non-randomized and single-group, and it has no separate control group. Its dose levels are part of the dose-finding description, not randomized controls. As a result, observed outcomes cannot be interpreted as a randomized estimate of the combination's effect relative to another treatment. The record does not describe an adjusted comparative method that would change this limitation.

What can a planning illustration tell a reader?

General explanation: power calculations describe how often a planned analysis would detect an effect under stated assumptions if the same study design were repeated. A planning sample size is not an observed result, and observed power is not a measure of how convincing the results are. The planning assumptions described for the illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set to a stated fraction of an observed effect. Time-to-event illustrations refer to a total number of events; other illustrations refer to participants per arm. These are hypothetical planning conventions. They do not match the actual single-group design, and the registry record does not report a trial-specific sample-size justification.

What methods are not reported?

The registry record does not report the statistical test or model for the primary endpoint, a prespecified rule for choosing the recommended dose, an approach to missing observations, analysis populations, or handling of multiple outcomes. It also does not provide a detailed plan for survival analysis, response analysis, or safety comparisons. General statistical practice cannot fill in these trial-specific omissions. Without those details and without posted endpoint results, readers cannot verify how estimates were obtained, assess their precision, or determine whether analyses followed a prespecified plan.

10. Multiplicity, Missing Data and Analysis Populations

Several outcomes are listed: the Phase I dose-selection primary endpoint and Phase II measures of progression-free survival, overall survival, best response, and adverse events. Considering multiple outcomes can raise a multiplicity issue: if many statistical tests are performed, the chance of at least one apparently noteworthy result can increase. General methods to address this include prespecifying a primary analysis or adjusting inference, but the registry record does not report whether any such approach was planned. It also reports no analyses, so there are no posted p-values or confidence intervals to assess for multiplicity.

Missing-data methods and analysis populations are not reported in the registry record. The entry does not state how participants who discontinue treatment, lack an outcome assessment, or have incomplete follow-up were handled. It also does not define an intention-to-treat, treated, evaluable, or other analysis population. These omissions are relevant to interpreting both the dose-finding endpoint and the listed Phase II outcomes. The total enrollment of 12 does not establish how many participants contributed data to each endpoint.

The primary endpoint description specifies dose-limiting toxicities in the first 4 weeks, but the record does not describe how missing or unevaluable observations within that window would affect dose selection. Nor does it report follow-up or censoring methods for time-to-event outcomes. These methods should not be inferred from the outcome names. With no posted analyses, the registry record does not allow assessment of whether missingness, multiplicity, or analysis-population choices affected reported estimates.

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: rash maculo-papular (16.7%), dyspnea (16.7%), abdominal pain (16.7%), diarrhea (16.7%), vomiting (16.7%).

The registry lists serious adverse event figures for Phase I dose levels 1 and 2. For each listed level, 6 participants are recorded as at risk; 2 are recorded as affected at dose level 1 and 1 at dose level 2. Deaths are listed for 2 participants at dose level 1 and 1 at dose level 2. These are descriptive counts in the registry, not randomized comparisons, and the record does not report a causal assessment linking the events or deaths to study treatment.

The listed top serious terms are Rash maculo-papular, Dyspnea, Abdominal Pain, Diarrhea, Vomiting, and Fever, each reported as 16.7%. The record does not establish from these figures whether the terms occurred in the same or different participants, how they were distributed across dose levels, or their timing. It also does not provide comparable serious-event figures for every described Phase I dose level in the listed groups.

Serious adverse events are not equivalent to all adverse events, and these figures should not be treated as a complete safety profile. The registry record does not report further detail needed to interpret event duration, severity grading, treatment discontinuation, or attribution. The listed counts describe what is recorded, without establishing a treatment effect or comparative risk.

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

The record shows that a Phase I/II study of LEE011 plus everolimus was conducted in metastatic pancreatic adenocarcinoma refractory to chemotherapy, with a primary objective of selecting a recommended Phase II dose using dose-limiting toxicities in the first 4 weeks. It records enrollment of 12 and describes several Phase I dose levels and a Phase II regimen using the recommended dose. The record is completed, but completion status does not itself provide the study's outcome findings.

The most important result for the stated primary objective—the selected dose—is not reported in the registry record. The listed Phase II outcomes also have no reported results. The posted serious adverse event figures are limited to two Phase I dose levels and should be read as descriptive counts, not as proof that treatment caused or did not cause an event. The deaths listed in those groups do not establish cause.

Because the study has no randomized control group, it cannot provide a randomized estimate of how the combination compares with another treatment. The dose-level groups are not a substitute for such a control. Any differences between them could be affected by non-random allocation or other factors, and no comparative analysis is reported.

General interpretation: an unreported result is not evidence that the result was favorable, unfavorable, or null. It means the registry entry does not provide the information needed to assess the estimate, its precision, or its robustness. The record supports a description of the study question and design, but not a conclusion about efficacy, comparative benefit, or the final recommended dose.

13. Why This Trial Matters Statistically

This study illustrates why the question attached to an endpoint matters. Its primary endpoint is dose selection based on dose-limiting toxicities during the first 4 weeks, whereas its listed Phase II outcomes concern survival, response, and adverse events. These answer different questions. A dose-finding objective cannot be interpreted as a test of comparative efficacy, and Phase II outcome labels do not supply results when none are reported.

It also illustrates the interpretive limits of a single-group, non-randomized design. Randomized controls help distinguish treatment-associated differences from differences that may arise because participant groups were formed differently. Here, no separate comparator is listed. Dose-level descriptions therefore should not be mistaken for equivalent randomized arms. The registry's safety counts are useful as descriptive information, but do not independently establish causal attribution or comparative safety.

Finally, a completed study record and a detailed list of planned outcomes do not guarantee that the results needed for statistical interpretation are present in the registry. Without the primary endpoint result, analysis methods, missing-data approach, and estimates with measures of precision, readers cannot judge the dose-selection conclusion or the strength of evidence for the listed Phase II outcomes. That distinction—between what the design set out to measure and what the record actually reports—is central to responsible reading of clinical trial statistics.

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 registry record leaves important trial-specific details unreported. It does not give the recommended Phase II dose, the observed dose-limiting toxicities, or the rules used to decide on a dose. It does not report results for progression-free survival, overall survival, best response, or the listed Phase II adverse-event outcome. Thus, the primary objective and secondary outcomes cannot be evaluated from the posted results in this record.

The study is non-randomized, unmasked, and single-group, without a separate control group. This limits comparative interpretation and leaves outcomes open to influences that a controlled comparison is designed to address. The record describes Phase I dose levels, but does not report how participants were assigned among all listed levels or how the dose-selection process proceeded. The serious adverse event group figures cover only two listed dose levels, and the registry does not explain their relationship to the total enrollment of 12.

Other limitations include absent detail on analysis populations, missing-data handling, endpoint definitions beyond the stated descriptions, survival follow-up and censoring, multiplicity, and statistical models. The registry record also does not report the trial-specific sample-size rationale or a detailed statistical analysis plan. These omissions prevent a full assessment of precision, robustness, and potential analysis choices. They should not be resolved by assuming conventional methods were used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: LEE011 Plus Everolimus in Patients With Metastatic Pancreatic Adenocarcinoma Refractory to Chemotherapy — NCT02985125.
• Registry record last updated 2026-04-07; status last verified 2026-03.
• Results first posted 2026-04-07.
• 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

NCT02985125 is a completed Phase I/II, single-group, non-randomized, open-label study sponsored by Georgetown University. It enrolled 12 participants with metastatic pancreatic adenocarcinoma refractory to chemotherapy. The primary objective was to determine the recommended Phase II dose of LEE011 with everolimus from dose-limiting toxicities during the first 4 weeks.

The registry describes oral LEE011 dose levels in Phase I and a Phase II regimen using the recommended dose, alongside everolimus 2.5mg. Listed Phase II outcomes include progression-free survival, overall survival, best response by RECIST v1.1 criteria, and adverse events by NCI CTCAE v4.03. Serious adverse event counts are listed for two Phase I dose levels. The selected dose and results for the primary and Phase II outcomes are not reported in the registry record.