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 TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer (NCT02586675), a na phase 1 study. The primary outcome is Recommended Phase II Dose (RP2D).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02586675 |
| Phase | Phase 1 |
| Condition | Breast Cancer, Breast Cancer - Female, Breast Cancer - Male |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | H. Lee Moffitt Cancer Center and Research Institute |
| Results posted | Yes |
2. Clinical Question
Population
Adults with advanced estrogen receptor-positive, HER2-negative breast cancer. The registry describes premenopausal and post-menopausal women and men as the intended population; the condition list includes breast cancer, breast cancer in females, and breast cancer in males.
Intervention
Ribociclib taken with tamoxifen. Goserelin was added for premenopausal or peri-menopausal participants. The trial included a Phase I dose-escalation portion followed by a Phase Ib dose-expansion portion.
Comparator
There was no separate comparator group in the registry design. The study is recorded as single group, with allocation listed as not applicable and no masking.
Primary question
What ribociclib dose should be recommended for Phase II use with tamoxifen, and what dose-limiting toxicities occur during the defined assessment period? The registry describes a target range of 400-600 mg and a dose-limiting toxicity assessment during the first 28 days of treatment.
This is a dose-finding question, rather than a randomized comparison of treatment strategies. The study was intended to assess ribociclib with tamoxifen and to identify a recommended Phase II dose, while also recording safety outcomes. Its secondary outcomes were progression-free survival and overall survival at six months. Those outcomes can describe what happened during follow-up, but the registry record does not report their numerical results or analyses.
The distinction between the intended clinical question and the available results matters. A dose range and rules for defining dose-limiting toxicity describe the study’s objective and measurement framework; they do not, by themselves, establish which dose was selected or how many participants experienced a dose-limiting toxicity. The registry record does not report a selected recommended Phase II dose or a dose-limiting toxicity count.
3. Trial Design
The registry records NCT02586675 as a completed Phase I study with an enrollment of 7. It was conducted as a single-group trial, with allocation listed as not applicable and masking listed as none. There was no randomized control group, so the design does not support a like-for-like comparison between study arms. The registry lists the start date as 2016-02-23 and primary completion as 2017-05-08.
The study description combines a Phase I dose-escalation portion with a Phase Ib dose-expansion portion. The intervention was ribociclib with tamoxifen. Goserelin was added for premenopausal or peri-menopausal participants. The arm description lists ribociclib as capsules or tablets for oral use at 400 mg or 600 mg on days 1-21 of each 28 day cycle or daily. It lists tamoxifen tablets for oral use at 20 mg daily. The record does not report a participant-level treatment schedule or clarify how the listed dosing options were assigned.
The primary outcome was the recommended Phase II dose, with a timeframe of up to 12 months and the population described as all participants. The registry’s dose-finding description says the Phase I portion was intended to confirm dose-limiting toxicity and the recommended Phase II dose for ribociclib with tamoxifen. The dose-limiting toxicity definition covers an adverse event or abnormal laboratory value considered reasonably related to study medication and occurring during the first 28 days of treatment, subject to the exclusions and specific grading criteria in the registry description.
Two secondary outcomes are listed: progression-free survival at six months and overall survival at six months. The record reports three outcome measures and zero analyses. It does not report detailed analysis methods, participant flow, or how many participants contributed data to each secondary outcome. Although the trial is marked completed, the record’s status alone does not supply the numerical outcome results that would be needed to assess dose selection or survival.
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 | Tamoxifen and Ribociclib With Goserelin |
|---|---|
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All 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.
Population: All participants.
| Characteristic | Unit | Tamoxifen and Ribociclib With Goserelin |
|---|---|---|
| Participants analysed | 7 | |
| Age, Continuous | years | 54 (SD 13.31) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended Phase II Dose (RP2D), measured over Up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | dose in mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the recommended Phase II dose (RP2D) of ribociclib when taken with tamoxifen. It is expressed in milligrams, and the registry describes a target range of 400-600 mg. This endpoint is used in early-phase dose-finding because a later-phase study needs a dose specified for further evaluation. The endpoint is not itself a measure of tumor response or survival.
The registry links dose selection to dose-limiting toxicity (DLT). A DLT is defined as an adverse event or abnormal laboratory value assessed as having a reasonable possibility of being related to study medication, rather than disease, disease progression, inter-current illness, or concomitant medications, and occurring within the first 28 days of treatment with ribociclib and tamoxifen. The listed criteria include prolonged grade 4 neutropenia, grade 3 thrombocytopenia with clinically significant bleeding, or grade 4 thrombocytopenia. Grading was to use NCI CTCAE version 4.03.
In general, a dose-finding endpoint combines tolerability information with the study’s dose-escalation approach to inform which dose merits further study. The registry record describes this purpose and the assessment rules, but does not report the observed DLT results or identify a selected RP2D. Therefore, the endpoint definition should not be mistaken for a reported dose-selection finding.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main interpretable results in the registry record are descriptive safety counts. In the single group, 7 participants were at risk for serious adverse events and 2 were reported as affected. For other adverse events, 7 participants were at risk and 7 were reported as affected. The record lists 0 deaths. These counts describe the participants represented in the posted safety results; they do not provide a comparison with another treatment group.
The serious-event terms listed include Gastrointestinal - Other, Gastroenteritis; Fatigue; Syncope; and Thromboembolic event, each with a reported percentage of 14.3%. Those term-level percentages are not a complete account of event severity, timing, duration, recurrence, or attribution. Nor does the listing establish that terms are mutually exclusive. The registry record does not give a fuller event-level account alongside these figures.
The primary outcome was recommended Phase II dose, but no selected dose or numerical DLT result is reported in the registry record. The stated range of 400-600 mg is part of the endpoint description, not evidence that a particular dose was selected. Likewise, the registry lists progression-free survival and overall survival at six months as secondary outcomes, but does not report numerical survival estimates, event counts, or uncertainty measures. The completion status cannot substitute for these missing outcome results.
The enrollment of 7 is important for interpreting precision. In general, results from a small study can be highly sensitive to the outcome of each participant, and a descriptive count cannot establish how frequently an event would occur in a broader population. This study also has no separate comparator group, so observed events cannot be contrasted with an untreated group or another regimen within this design. The figures should therefore be read as a record of what was reported for this study, not as a comparative estimate.
The registry records zero analyses. It does not report inferential estimates such as confidence intervals or hypothesis tests for the outcomes. In general, a confidence interval communicates the range of values compatible with an estimate under a specified analysis; without an estimate and analysis, precision cannot be assessed in that way. No claim about treatment benefit or comparative effectiveness follows from the posted safety counts or the trial’s completed status.
Overall, the record documents a small early-phase study with a dose-finding objective, a defined DLT framework, and descriptive adverse-event counts. It does not report the central dose-selection result or numerical findings for the listed survival outcomes. Readers should distinguish those absent results from the study’s stated objectives and planned outcome definitions.
9. Statistical Methods Explained
The registry describes a single-group Phase I dose-escalation study followed by a Phase Ib dose-expansion portion. These features explain the study’s early-phase, dose-finding purpose, but they do not supply a detailed statistical analysis plan. The record lists zero analyses. Methods that would be needed to reproduce an outcome analysis or evaluate its uncertainty are not reported in the registry record.
What does dose escalation address?
In general, dose escalation explores how tolerability changes across dose levels and uses the observed safety experience to inform a dose for further evaluation. Dose-limiting toxicity criteria make that process more operational by specifying which events count for the decision and the period in which they are assessed. In this study, the registry defines the DLT period as the first 28 days of treatment and names specific blood-count toxicity criteria, with grading based on NCI CTCAE version 4.03.
Those definitions are not a report of what happened. To understand the actual dose-escalation result, readers would need the dose levels each participant received, the number evaluable at each level, DLT outcomes, and the decision process leading to the recommended Phase II dose. Such results are not reported in the registry record. The stated 400-600 mg range belongs to the endpoint description and should not be read as a confirmed selected dose.
Why is the design not a treatment comparison?
In general, a randomized comparison aims to make treatment groups comparable on average, so differences in outcomes can be interpreted against the assigned alternatives, subject to the trial’s assumptions and conduct. This registry describes one group, allocation as not applicable, and no masking. There is therefore no concurrent control group for a direct treatment contrast. The skip note in the record also cautions that arms are not a like-for-like control comparison. Safety counts from this study should be interpreted descriptively, not as an estimate of a difference between regimens.
The treatment description includes ribociclib and tamoxifen, with goserelin added for premenopausal or peri-menopausal participants. In general, when treatment components differ according to participant characteristics, clear reporting of who received each component helps readers understand the population exposed to each regimen. Participant-level details and subgroup results are not reported in the registry record.
How should counts and percentages be read?
In general, an adverse-event count is meaningful alongside its denominator and the event definition. The registry reports 7 participants at risk for serious adverse events, 2 affected, and 7 at risk for other adverse events, with 7 affected. It also reports 0 deaths. These are observed counts for the single group; they are not adjusted estimates. The listed serious-event terms carry percentages of 14.3% each. The registry does not provide enough detail to determine from those terms alone whether participants experienced multiple listed events, how events were classified, or how long participants were observed for each safety outcome.
For small samples, one participant’s outcome can noticeably change a count-based summary. In general, uncertainty intervals can help communicate the imprecision around an estimated event frequency, but no such intervals are reported in the registry record. No additional estimates should be inferred from the counts alone.
What can the survival outcomes establish?
The listed secondary outcomes are progression-free survival and overall survival at six months. In general, progression-free survival concerns the time until disease progression or death, while overall survival concerns time until death from any cause. These concepts do not establish which endpoint definition or censoring rules were used in a specific analysis. The registry record does not report numerical survival results, event counts, censoring details, or analysis methods for these outcomes.
Time-to-event analysis commonly accounts for differing follow-up and participants whose event has not been observed by the analysis cutoff. In general, a Kaplan-Meier estimate is one approach to describing survival over time, while regression approaches may estimate associations under stated assumptions. The record does not say whether either approach was used. No such method or estimate should be attributed to this trial on the basis of the listed outcomes alone.
What does the absence of analyses mean?
The record lists zero analyses, so it does not provide inferential results to assess through p-values or confidence intervals. In general, a p-value summarizes how incompatible data are with a specified null model under its assumptions; it is not a measure of clinical importance. A confidence interval communicates uncertainty around an estimate under a specified method. Neither quantity can be reconstructed responsibly without the underlying analysis details and results.
The record also includes a sample-size planning assumption describing an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that time-to-event planning uses a total number of events and other planning quantities use participants per arm. These are planning conventions, not a description of the design of this single-group study, and the record does not report a usable observed-effect value or a trial-specific sample-size justification. Such planning illustrations are not observed power and do not explain why enrollment was 7.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures: recommended Phase II dose as the primary outcome, plus progression-free survival and overall survival at six months as secondary outcomes. It reports zero analyses. No statistical plan for controlling multiplicity is reported in the registry record. In general, when several outcomes or comparisons are tested, multiplicity methods may be used to address the increased chance of a false-positive finding across tests. That concern cannot be evaluated from a list of outcomes alone, especially when no analyses or inferential results are reported.
Missing-data handling is not reported in the registry record. The record does not describe how missing endpoint measurements, incomplete follow-up, or participants who could not be evaluated for DLT were handled. It also does not report the amount or pattern of missingness. In general, these details matter because missing outcomes can affect both the denominator and the interpretation of an estimate; the direction and extent of any effect depend on circumstances that are not documented.
The primary endpoint population is described as all participants. That phrase does not provide further detail about the analysis population or specify whether every enrolled participant contributed to each endpoint. The registry record does not define analysis populations for the secondary outcomes, describe censoring rules, or provide a participant flow account. It also does not report an intention-to-treat, per-protocol, or safety-population definition. These omissions limit assessment of who contributed to each posted result and how outcome data were analyzed.
In general, a transparent analysis plan identifies endpoint definitions, analysis populations, missing-data procedures, and any multiplicity strategy before results are interpreted. Those details are not reported in the registry record, so no claim about their use can be made.
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 |
|---|---|---|---|
| Tamoxifen and Ribociclib With Goserelin | 2 | 7 | 28.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tamoxifen and Ribociclib With Goserelin | 0 of 7 |
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 |
|---|---|
| Tamoxifen and Ribociclib With Goserelin | 7 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Tamoxifen and Ribociclib With Goserelin |
|---|---|---|
| Gastrointestinal - Other, Gastroenteritis | Gastrointestinal disorders | 1 of 7 |
| Fatigue | General disorders | 1 of 7 |
| Syncope | Nervous system disorders | 1 of 7 |
| Thromboembolic event | Vascular disorders | 1 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tamoxifen and Ribociclib With Goserelin |
|---|---|---|
| Neutrophil count decreased | Investigations | 4 of 7 |
| White blood cell decreased | Investigations | 4 of 7 |
| Alanine aminotransferase increased | Investigations | 3 of 7 |
| Aspartate aminotransferase increased | Investigations | 3 of 7 |
| Platelet count decreased | Investigations | 3 of 7 |
| Dehydration | Metabolism and nutrition disorders | 3 of 7 |
| Electrocardiogram QT corrected interval prolonged | Investigations | 2 of 7 |
| Hypomagnesemia | Metabolism and nutrition disorders | 2 of 7 |
| Dizziness | Nervous system disorders | 2 of 7 |
| Vomiting | Gastrointestinal disorders | 2 of 7 |
Serious events with the highest arm-level rate: gastrointestinal - other, gastroenteritis (14.3%), fatigue (14.3%), syncope (14.3%), thromboembolic event (14.3%).
The registry reports a single safety group titled Tamoxifen and Ribociclib With Goserelin. Seven participants were at risk for serious adverse events; 2 were reported as affected. For other adverse events, 7 were at risk and 7 were affected. The death count was 0. These figures are descriptive counts for the reported group and do not compare safety against another group.
Four serious-event terms are listed with a reported frequency of 14.3% each: Gastrointestinal - Other, Gastroenteritis; Fatigue; Syncope; and Thromboembolic event. These term-level entries should not be treated as a complete safety profile. The record does not report the number of occurrences, timing, duration, outcome, relatedness, or severity grade for each term in the listed results. The term listing alone also does not show whether participants experienced more than one listed event.
In general, “at risk” identifies the group used as the denominator for an event summary, while “affected” indicates how many participants were recorded with the event category. A count from a small group has limited precision and does not establish a population rate. The record’s safety figures should be understood as the events reported for this study, not as proof that an event is caused by or unrelated to the study treatment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, single-group Phase I study evaluated ribociclib with tamoxifen, with goserelin added for premenopausal or peri-menopausal participants. It enrolled 7 participants and set out to identify a recommended Phase II dose using a dose-limiting toxicity framework. The record also lists six-month progression-free survival and overall survival as secondary outcomes and reports descriptive safety counts.
What the record does not establish is the selected recommended Phase II dose. Although 400-600 mg appears in the primary endpoint description, the record does not report which dose, if any, was recommended. It also does not report the observed DLT count or numerical survival results. A stated objective is not the same as a result, and the completed status does not fill in these missing findings.
The posted safety counts indicate that 2 of 7 participants were reported as affected by serious adverse events, 7 of 7 by other adverse events, and 0 deaths were recorded. These are descriptive data from one small group. They do not show how those counts compare with another therapy, what would have happened without treatment, or whether an individual event was caused by a particular study drug. The term-level serious-event percentages likewise do not provide a complete account of the clinical course or event burden.
In general, statistical evidence about treatment effects depends on a clearly specified comparison, outcome definitions, analysis methods, and uncertainty estimates. Those elements are not all available in the registry record. No efficacy conclusion or comparative treatment claim should be drawn from the information reported. The most appropriate reading is that the registry documents the trial’s dose-finding purpose and some safety results, while leaving the primary dose-selection result and numerical secondary-outcome findings unreported.
13. Why This Trial Matters Statistically
Early-phase trials answer a different statistical question from confirmatory trials. This study’s primary objective was to identify a recommended Phase II dose of ribociclib with tamoxifen, using a specified DLT definition. That focus makes the relationship between the dose-escalation process, toxicity assessment window, and final dose-selection result central to interpretation. The registry record describes the framework but does not report the dose ultimately selected or the DLT results that would explain the decision.
The single-group design is also statistically important. Without a separate comparator, the posted safety counts describe events in the study group but cannot quantify how those events differ from an alternative regimen. This is not a flaw in the design for its stated dose-finding purpose; it does, however, limit the kinds of comparative conclusions that can be supported. Design and question must be read together.
The small enrollment of 7 makes descriptive reporting especially important. In general, limited sample sizes can leave event frequencies imprecise and make each participant’s outcome influential. Counts, denominators, definitions, follow-up, and uncertainty all help readers judge what a small study can and cannot show. Here, the safety denominators and counts are reported, but no inferential estimates are given.
The case also illustrates why outcome registration and outcome results are distinct. The listed survival endpoints show what the study intended to measure, but without numerical estimates and methods they do not answer how participants fared on those outcomes. The record’s zero analyses and the absence of a reported RP2D mean that the central statistical result remains unavailable in the record, even though the trial is marked completed.
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 enrollment of 7 limits how much can be learned from the reported safety counts. A small single-group sample can describe what was recorded among participants, but it offers limited precision for characterizing less common events or outcomes in a wider population. The registry record does not report uncertainty intervals for the safety summaries.
There is no separate comparator group. As a result, the safety figures cannot be used to estimate a difference between this regimen and another treatment. The record also describes goserelin as added for premenopausal or peri-menopausal participants, but does not report participant-level treatment details or outcomes by subgroup. The effects of each individual treatment component cannot be separated from these data.
The most important trial-specific reporting limitation is that the primary outcome is not reported as a result. The registry describes a 400-600 mg target range and DLT criteria but does not state a selected RP2D or provide DLT counts. Numerical findings for progression-free survival and overall survival at six months are also not reported. The record does not give event-level safety details sufficient to assess timing, duration, severity, or attribution of the listed events.
Further limitations include the absence of reported analysis methods, missing-data procedures, multiplicity handling, censoring rules, and detailed analysis populations. The record does not provide enough information to assess whether follow-up or outcome availability differed among participants. These limitations concern what can be interpreted from the registry record; they do not establish that an analysis or additional data do not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: TEEL Study- Phase 1 Tamoxifen and Ribociclib (LEE011) in Advanced ER+ (HER2 Negative) Breast Cancer — NCT02586675.
- Registry record last updated 2022-01-21; status last verified 2022-01.
- Results first posted 2019-06-03.
- 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
NCT02586675 is recorded as a completed Phase I, single-group study with an enrollment of 7. It evaluated ribociclib with tamoxifen in advanced ER-positive, HER2-negative breast cancer, adding goserelin for premenopausal or peri-menopausal participants. The primary outcome was recommended Phase II dose, with DLT criteria defined for the first 28 days of treatment. Progression-free survival and overall survival at six months were listed as secondary outcomes.
The registry reports 2 participants affected by serious adverse events among 7 at risk, 7 affected by other adverse events among 7 at risk, and 0 deaths. It lists four serious-event terms at 14.3% each. No numerical RP2D or DLT result, survival estimate, or analysis is reported in the registry record. The design has no comparator group, and the safety results are descriptive.