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 Evaluating Temsirolimus (CCI-779) In Breast Neoplasms (NCT00062751), a randomized phase 2 study. The primary outcome is Percentage of Participants With Objective Response (OR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00062751 |
| Phase | Phase 2 |
| Condition | Breast Neoplasms |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 108 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wyeth is now a wholly owned subsidiary of Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled postmenopausal women with locally advanced or metastatic breast cancer. The registry describes the intended participants as people appropriate to receive endocrine therapy for advanced disease. The primary endpoint population was the intent-to-treat population, defined in the record as all participants randomized in the study. The record does not report further eligibility details or baseline characteristics for the randomized population.
Intervention
The trial evaluated letrozole combined with oral temsirolimus, also called CCI-779, using different doses and schedules. The official title describes two dose levels and schedules in combination with letrozole. The registry’s adverse-event entries include several regimen descriptions, including daily and intermittent schedules. Full descriptions of the randomized arms are not reported in the registry record.
Comparator
The stated comparator was letrozole alone. The study was randomized and open-label, so participants and investigators were not masked according to the registry. The record describes a later cross-over regimen in one adverse-event group, but the complete cross-over rules and their relationship to the original randomized assignments are not reported.
Primary question
The primary endpoint was the percentage of participants with an objective response, defined as a confirmed complete or partial response. The study sought to evaluate preliminary activity and pharmacokinetics for temsirolimus regimens with letrozole compared with letrozole alone. However, the registry states that the final efficacy analysis was not conducted because development of temsirolimus for breast cancer was terminated. Consequently, the record does not report the primary response estimates needed to assess the randomized comparison.
3. Trial Design
This was a randomized, open-label, parallel-group Phase 2 study. Its official title describes letrozole in combination with two dose levels and schedules of oral temsirolimus, or letrozole alone, in postmenopausal women with locally advanced or metastatic breast cancer. The registry reports enrollment of 108 participants and a completed study status. It does not report the number randomized to each original arm or provide complete arm descriptions.
The study was intended to evaluate preliminary activity and pharmacokinetics. The primary endpoint concerned objective response, while listed secondary outcomes covered clinical benefit, time to disease progression, time to treatment failure, freedom from progression, duration of response, survival, and health-related outcomes. The registry lists health assessments using EQ-5D and the EORTC QLQ BR23. Although the record states there were 12 outcome measures, the final efficacy analysis was not conducted. The detailed results for these other outcomes are not reported in the registry record.
The primary outcome timeframe began at baseline and included assessments every 4 cycles, with a cycle defined as 14 days, up to Cycle 25, followed by assessments every 6 cycles until disease progression. The response definition required confirmation at least 4 weeks after criteria were first met. The record identifies the intent-to-treat population as all randomized participants for this endpoint.
Some safety entries describe regimens and groups after cross-over, including a group labeled as letrozole alone prior to cross-over to intermittent temsirolimus and a separate after-cross-over group. These entries should not be treated as a complete account of the original randomized design. The arm allocation details, timing of cross-over, and analysis approach for these safety groups are not reported in the registry record.
The study start is recorded as 2002-12 and primary completion as 2005-04. The registry does not report the protocol’s sample-size justification, the planned statistical analysis methods, or whether interim analyses were specified or conducted.
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.
Before assignment: In the initial protocol, doses of CCI-779 were 25 mg daily and 75 mg intermittent; per protocol amendment, dosing was modified to 10 mg daily and 30 mg intermittent. All dose levels are included in the reporting groups.
Overall Study
| Stage | Let 2.5 mg Plus 10 mg Daily CCI-779 | Let 2.5 mg Plus 30 mg Intermittent CCI-779 | Let 2.5 mg Alone / Cross-over to 75 mg Intermittent CCI-779 | Let 2.5 mg Plus 25mg Daily CCI-779 | Let 2.5 mg Plus 75 mg Intermittent CCI-779 |
|---|---|---|---|---|---|
| STARTED | 33 | 30 | 33 | 6 | 6 |
| COMPLETED | 0 | 0 | 3 | 1 | 0 |
| NOT COMPLETED | 33 | 30 | 30 | 5 | 6 |
Reasons for not completing this period:
| Reason | Let 2.5 mg Plus 10 mg Daily CCI-779 | Let 2.5 mg Plus 30 mg Intermittent CCI-779 | Let 2.5 mg Alone / Cross-over to 75 mg Intermittent CCI-779 | Let 2.5 mg Plus 25mg Daily CCI-779 | Let 2.5 mg Plus 75 mg Intermittent CCI-779 |
|---|---|---|---|---|---|
| Disease progression | 24 | 17 | 24 | 2 | 2 |
| Adverse Event | 4 | 7 | 2 | 2 | 2 |
| Other | 2 | 3 | 1 | 0 | 1 |
| Withdrawal by Subject | 1 | 2 | 2 | 1 | 0 |
| Symptomatic deterioration | 1 | 1 | 0 | 0 | 1 |
| Death | 1 | 0 | 1 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat population (ITT) defined as all participants randomized in the study. Final efficacy analysis was not conducted because the development of temsirolimus (CCI-779) for the treatment of breast cancer was terminated.
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 | Let 2.5 mg Plus 10 mg Daily CCI-779 | Let 2.5 mg Plus 30 mg Intermittent CCI-779 | Let 2.5 mg Alone / Cross-over to 75 mg Intermittent CCI-779 | Let 2.5 mg Plus 25mg Daily CCI-779 | Let 2.5 mg Plus 75 mg Intermittent CCI-779 | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 33 | 30 | 33 | 6 | 6 | 108 | |
| Age Continuous | years | 62.21 (SD 11.87) | 62.83 (SD 8.39) | 60.85 (SD 9.79) | 61.83 (SD 9.83) | 60.00 (SD 9.65) | 61.82 (SD 9.98) |
| Sex/Gender, Customized: Female | participants | 33 | 30 | 33 | 6 | 6 | 108 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Objective Response (OR), measured over Baseline, every 4 cycles (1 cycle is defined as a 14 day duration) up to Cycle 25, then every 6 cycles until disease progression.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with an objective response. An objective response was defined as a complete response or partial response, with confirmation by an assessment performed no less than 4 weeks after response criteria were first met. A complete response required disappearance of all target and non-target lesions and normalization of tumor marker level. A partial response required at least a 30% decrease in the sum of the longest diameters of target lesions, using the screening sum as the reference.
The registry describes target lesions as measurable lesions selected to represent involved organs, with up to 5 lesions per organ and 10 lesions in total if possible. Other lesions were classified as non-target lesions. The endpoint therefore uses defined radiographic and tumor-marker criteria rather than an unstructured judgment of improvement. Requiring confirmation is intended to distinguish a response that is maintained on assessment from an initial finding that is not confirmed.
Response percentage is a binary-outcome summary: each participant is classified according to whether the defined response occurred. The endpoint is relevant to the study’s stated purpose of evaluating preliminary activity. It does not, by itself, describe how long a response lasts or whether disease progression is delayed; those topics were listed among the secondary outcomes. The registry does not report the final efficacy analysis or the primary endpoint estimates, so the response percentage and its precision cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of letrozole alone with letrozole plus temsirolimus regimens, but it does not report a final efficacy analysis. It explicitly states that the final efficacy analysis was not conducted because development of temsirolimus for breast cancer was terminated. As a result, the central numerical evidence needed to interpret the primary endpoint is not reported in the registry record: response counts or percentages by randomized arm, confidence intervals, and a comparative estimate are absent.
This absence is different from a result showing no responses or no difference. Without the final endpoint estimates, the posted record does not establish the observed response pattern in the randomized groups. It also does not support a conclusion about the direction or size of any treatment contrast. The reason for stopping development is stated, but that reason is not an efficacy finding and should not be read as evidence for or against a difference in response.
The endpoint definition is detailed enough to identify what would have been counted as a response. Complete and partial responses had specified criteria, and responses had to be confirmed at least 4 weeks after the criteria were first met. The assessment schedule is also described. These definitions clarify the intended measurement, but they cannot substitute for the missing participant-level outcome summaries or the final analysis.
The listed secondary outcomes indicate that the trial planned to consider disease progression, treatment failure, response duration, survival, and health outcomes. Their presence in the registry does not mean their results are available. The final results for these outcomes are not reported in the registry record. The record also lists 12 outcome measures but reports zero analyses. It therefore offers no posted analysis with which to assess estimates, uncertainty, or consistency across endpoints.
The adverse-event entries do provide counts for serious adverse events and other adverse events in labeled groups. Those counts are descriptive safety information, not an efficacy analysis. Some entries are explicitly associated with cross-over or post-cross-over treatment, so they do not all correspond straightforwardly to the original randomized comparison. The record does not provide enough detail to reconstruct comparative risks or to determine how the listed groups were formed for analysis. The serious-event term percentages are listed without a clear denominator in the available description.
Overall, the registry supports a description of the trial question, design, endpoint rules, and selected safety counts. It does not provide the final primary efficacy results. Statistical uncertainty about objective response therefore cannot be quantified from this record, and neither a positive nor a negative efficacy conclusion follows from the missing analysis.
9. Statistical Methods Explained
What does the endpoint estimate?
The primary outcome is a binary participant-level measure: whether a participant met the confirmed objective-response definition. A percentage summarizes the share of the analysis population classified as having a response. This kind of summary is easy to interpret as a frequency in the trial population, but its meaning depends on clear eligibility, assessment rules, and a defined analysis population. The registry identifies the intent-to-treat population as all randomized participants. It does not report the final response counts or percentages.
For a binary endpoint, a confidence interval describes uncertainty around an estimated response percentage. In general, a narrower interval indicates greater precision and a wider interval indicates less precision. The registry identifies a 95% confidence interval as the endpoint’s dispersion measure, but the final efficacy analysis was not conducted and no interval estimate is reported. Therefore, the intended uncertainty measure cannot be inspected or interpreted from the posted record.
Why does confirmation matter?
The response definition requires confirmation at least 4 weeks after the criteria were first met. In general, confirmation reduces reliance on a single assessment and makes the endpoint more resistant to an isolated measurement or classification. The record also specifies what qualifies as complete or partial response and distinguishes target from non-target lesions. Such operational rules help make endpoint classification more consistent. They do not, however, resolve questions about missing assessments, assessment review procedures, or how unconfirmed findings were handled in the final analysis; those details are not reported in the registry record.
What does randomization contribute?
Random allocation is intended to create groups that can be compared without choosing treatment according to participant prognosis. In general, this supports an interpretation of between-group differences as a randomized treatment contrast, subject to the conduct and analysis of the trial. The record identifies the study as randomized and parallel, but the original allocation counts and full arm descriptions are not reported. Since the final primary analysis is absent, there is no posted estimate of a randomized contrast to interpret.
Open-label design means the registry lists masking as none. In general, knowledge of assigned treatment can influence behavior, care, reporting, or assessment, depending on the outcome and trial procedures. The response endpoint uses defined lesion criteria, which may constrain some subjectivity, but the registry does not report whether response assessments were independently reviewed or blinded. It would be inappropriate to assume such procedures.
What can the safety counts tell readers?
Safety counts describe participants recorded with events within the labeled groups. In general, a count requires its denominator and a clear observation period to support a rate interpretation. Counts from groups with different exposure histories or cross-over status may not be directly comparable. Here, the record supplies at-risk and affected counts for serious and other adverse events in several named groups, including cross-over-related entries. It does not provide enough detail about follow-up, event coding, or group construction to interpret these as a complete randomized comparison.
Over-dispersion is a general statistical issue when variation in observed outcomes exceeds what a simple model assumes. It can make model-based uncertainty too small if not accounted for. The registry does not report a model for the primary endpoint, and no final efficacy analysis is available. It is therefore not possible to determine whether over-dispersion was relevant to a particular analysis or how uncertainty was estimated beyond the stated intended 95% confidence interval.
Why do analysis populations matter?
An intent-to-treat analysis generally retains participants in the groups to which they were randomized, regardless of later treatment changes. This approach preserves the randomized comparison more directly than an analysis based only on treatment received. The registry defines the primary endpoint population as all randomized participants. However, it does not report the number included in each arm, whether every randomized participant had an evaluable response assessment, or how missing response information was handled. The stated population definition alone does not establish how the absent final analysis would have treated incomplete data.
In general, missing outcome data can affect an estimated response percentage if participants with unavailable assessments differ from those with observed assessments. Methods can range from explicit assumptions and imputation to sensitivity analyses, but the appropriate approach depends on the protocol and data. The registry does not report the missing-data strategy or the amount and pattern of missing primary endpoint data. No assumptions should be attributed to the trial without that information.
What does the planning illustration represent?
Sample-size illustrations are planning calculations, not observed trial results and not evidence that a trial had a particular probability of success. The registry’s description of planning assumptions refers to a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of an observed effect. The primary endpoint is excluded from the reduced comparison because it has several categories or time points, and no final efficacy analysis was conducted. The registry does not report the trial’s own sample-size justification. A planning illustration should therefore not be presented as the trial’s original design calculation or as observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes in addition to the primary objective-response endpoint. These include clinical benefit, time to disease progression, time to treatment failure, freedom from progression, duration of response, survival, and health-related outcomes. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if each is interpreted separately without an appropriate analysis plan. In general, multiplicity methods can address this issue, but the choice depends on the planned hypotheses and testing hierarchy. The registry does not report a multiplicity strategy, so no adjustment or testing sequence should be assumed.
The record states that the final efficacy analysis was not conducted because development of temsirolimus for breast cancer was terminated. It lists 12 outcome measures and zero analyses. It does not report final estimates or confidence intervals for the primary or secondary outcomes. This limits interpretation not only of multiplicity but also of the underlying effect estimates: without posted analyses, readers cannot assess which endpoints were evaluated, how uncertainty was quantified, or whether results were consistent.
The primary endpoint population is defined as all participants randomized. This is a stated intent-to-treat definition, but the registry does not report how missing or unevaluable response assessments were handled, nor does it describe the amount or pattern of missing data. The protocol’s analysis populations beyond this definition, including any per-protocol or safety populations, are not reported in the registry record.
Cross-over appears in the adverse-event group descriptions, but the registry does not describe how cross-over was handled for efficacy outcomes or how it affected the definition of analysis groups. No interim-analysis plan, stopping rule, or detailed statistical analysis plan is reported. The reason given for not conducting final efficacy analysis is termination of development; further decisions or analytical procedures are not reported.
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 |
|---|---|---|---|
| Let 2.5 mg Plus 10 mg Daily CCI-779 | 12 | 33 | 36.4% |
| Let 2.5 mg Plus 30 mg Intermittent CCI-779 | 10 | 30 | 33.3% |
| Let 2.5 mg Alone Prior to Cross-over to 75 mg Intermit CCI-779 | 9 | 33 | 27.3% |
| After Cross-over to 75 mg Intermittent CCI-779 | 1 | 18 | 5.6% |
| Let 2.5 mg Plus 25mg Daily CCI-779 | 2 | 6 | 33.3% |
| Let 2.5 mg Plus 75 mg Intermittent CCI-779 | 1 | 6 | 16.7% |
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 |
|---|---|
| Let 2.5 mg Plus 10 mg Daily CCI-779 | 33 of 33 |
| Let 2.5 mg Plus 30 mg Intermittent CCI-779 | 30 of 30 |
| Let 2.5 mg Alone Prior to Cross-over to 75 mg Intermit CCI-779 | 32 of 33 |
| After Cross-over to 75 mg Intermittent CCI-779 | 16 of 18 |
| Let 2.5 mg Plus 25mg Daily CCI-779 | 6 of 6 |
| Let 2.5 mg Plus 75 mg Intermittent CCI-779 | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Let 2.5 mg Plus 10 mg Daily CCI-779 | Let 2.5 mg Plus 30 mg Intermittent CCI-779 | Let 2.5 mg Alone Prior to Cross-over to 75 mg Intermit CCI-779 | After Cross-over to 75 mg Intermittent CCI-779 | Let 2.5 mg Plus 25mg Daily CCI-779 | Let 2.5 mg Plus 75 mg Intermittent CCI-779 |
|---|---|---|---|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 33 | 1 of 30 | 0 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
| Diarrhea | Gastrointestinal disorders | 0 of 33 | 1 of 30 | 1 of 33 | 1 of 18 | 0 of 6 | 0 of 6 |
| Hypercalcemia | Metabolism and nutrition disorders | 1 of 33 | 1 of 30 | 1 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
| Cellulitis | General disorders | 2 of 33 | 0 of 30 | 0 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
| Death | General disorders | 1 of 33 | 0 of 30 | 1 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
| Infection | General disorders | 0 of 33 | 1 of 30 | 0 of 33 | 0 of 18 | 0 of 6 | 1 of 6 |
| Sepsis | General disorders | 1 of 33 | 0 of 30 | 0 of 33 | 0 of 18 | 0 of 6 | 1 of 6 |
| Mucositis | Gastrointestinal disorders | 0 of 33 | 0 of 30 | 0 of 33 | 0 of 18 | 1 of 6 | 1 of 6 |
| Spinal cord compression | Nervous system disorders | 0 of 33 | 0 of 30 | 2 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
| Accidental injury | General disorders | 0 of 33 | 1 of 30 | 0 of 33 | 0 of 18 | 0 of 6 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Let 2.5 mg Plus 10 mg Daily CCI-779 | Let 2.5 mg Plus 30 mg Intermittent CCI-779 | Let 2.5 mg Alone Prior to Cross-over to 75 mg Intermit CCI-779 | After Cross-over to 75 mg Intermittent CCI-779 | Let 2.5 mg Plus 25mg Daily CCI-779 | Let 2.5 mg Plus 75 mg Intermittent CCI-779 |
|---|---|---|---|---|---|---|---|
| Asthenia | General disorders | 15 of 33 | 21 of 30 | 20 of 33 | 10 of 18 | 5 of 6 | 6 of 6 |
| Diarrhea | Gastrointestinal disorders | 13 of 33 | 15 of 30 | 6 of 33 | 9 of 18 | 4 of 6 | 2 of 6 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 11 of 33 | 13 of 30 | 12 of 33 | 5 of 18 | 4 of 6 | 2 of 6 |
| Mucositis | Gastrointestinal disorders | 10 of 33 | 15 of 30 | 2 of 33 | 10 of 18 | 4 of 6 | 4 of 6 |
| Pain | General disorders | 12 of 33 | 12 of 30 | 12 of 33 | 4 of 18 | 1 of 6 | 1 of 6 |
| Peripheral edema | Metabolism and nutrition disorders | 16 of 33 | 11 of 30 | 5 of 33 | 4 of 18 | 4 of 6 | 2 of 6 |
| Headache | General disorders | 11 of 33 | 11 of 30 | 10 of 33 | 4 of 18 | 2 of 6 | 2 of 6 |
| Rash | Skin and subcutaneous tissue disorders | 7 of 33 | 13 of 30 | 6 of 33 | 7 of 18 | 4 of 6 | 2 of 6 |
| Nausea | Gastrointestinal disorders | 7 of 33 | 11 of 30 | 10 of 33 | 5 of 18 | 2 of 6 | 3 of 6 |
| Back pain | General disorders | 9 of 33 | 10 of 30 | 12 of 33 | 3 of 18 | 1 of 6 | 1 of 6 |
Serious events with the highest arm-level rate: infection (16.7%), sepsis (16.7%), septic shock (16.7%), mucositis (16.7%), anemia (16.7%).
The registry lists serious adverse-event counts and other adverse-event counts for several labeled groups. For example, the group labeled Let 2.5 mg Plus 10 mg Daily CCI-779 has 12 participants affected by serious adverse events among 33 at risk, and 33 affected by other adverse events among 33 at risk. The Let 2.5 mg Plus 30 mg Intermittent CCI-779 group lists 10 of 30 affected by serious adverse events and 30 of 30 by other adverse events. These are the counts recorded for those labels; they should not be read as efficacy outcomes.
Other entries include a letrozole-alone period prior to cross-over and a separate after-cross-over group, as well as additional dose labels. Because exposure histories and group definitions differ, the entries are not necessarily comparable as original randomized arms. The registry does not report enough information about observation periods, event collection, or group construction to support a fuller comparative interpretation.
The listed serious-event terms each carry a recorded value of 16.7%, including infection, sepsis, septic shock, mucositis, anemia, and lung infiltration NOS. The denominator and the relationship between those term percentages and the overall group counts are not reported in the registry record. Death counts are recorded as null, so a numerical death result is not reported.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, open-label Phase 2 trial was designed to compare letrozole alone with letrozole plus temsirolimus regimens in postmenopausal women with locally advanced or metastatic breast cancer. It also defines the primary outcome as the percentage of participants with a confirmed objective response and describes the planned assessment schedule and response criteria. These details explain what the study intended to measure.
The record does not establish the observed primary response result. It states that a final efficacy analysis was not conducted after development of temsirolimus for breast cancer was terminated. No response estimates, confidence intervals, or comparative analysis are reported. The absence of those results cannot be translated into a finding of no response, no difference, or evidence favoring one regimen. It means the registry record does not supply the final efficacy analysis needed to answer the primary question.
The safety entries offer counts for serious and other adverse events in named groups. They are useful as descriptions of what the record lists, but they do not by themselves provide a complete account of comparative safety. Some groups involve cross-over, and details of exposure duration, event ascertainment, and the construction of the groups are not reported. The serious-event term percentages are also listed without a clear denominator in the available record.
More broadly, a trial’s endpoint definition and randomized design do not substitute for its outcome estimates. Interpretation requires the analysis results and enough information to understand the population included, missing data, and uncertainty. Those elements are not available for the primary efficacy endpoint in this registry record. The trial can therefore be characterized by its intended comparison and measurement framework, but its primary efficacy findings cannot be summarized from the posted record.
13. Why This Trial Matters Statistically
This trial illustrates why registry design information and completed efficacy results should be kept distinct. The record specifies a randomized comparison, an intended population, a response definition, and an assessment schedule. Those elements clarify the research question and what would count as an objective response. Yet the record also states that final efficacy analysis was not conducted. Without those estimates, the detailed endpoint criteria cannot answer whether or how the randomized groups differed.
The distinction is important for statistical interpretation. A missing analysis is not a null result. Nor can the reason for ending development be treated as a substitute for a response estimate or confidence interval. Readers need to distinguish what the registry says was planned from what it reports as analyzed. Here, the stated endpoint framework is available, but the primary efficacy result is not.
The record also demonstrates how safety summaries can be difficult to compare when labels include different treatment histories. Entries for groups before and after cross-over appear alongside regimen-specific groups. Without complete definitions of exposure and analysis populations, counts should be read as descriptive registry entries rather than as a clean randomized contrast.
For clinical researchers and biostatisticians, the trial is therefore a useful example of the limits of partial registry results. Randomization, prespecified-looking endpoint detail, and safety counts do not ensure that a final comparative analysis is available. The key statistical question is not only what was measured, but whether the resulting estimates and uncertainty were reported. In this record, the primary efficacy analysis is expressly absent, so conclusions must remain limited to the design and descriptive information recorded.
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 principal limitation is the absence of a final efficacy analysis. The registry states that development of temsirolimus for breast cancer was terminated and that the final efficacy analysis was not conducted. Consequently, the primary objective-response estimates and their 95% confidence intervals are not reported. The record does not support a numerical efficacy comparison between randomized groups.
The registry reports enrollment of 108 participants, but does not report the number randomized to each original arm or complete arm descriptions. Although the official title describes combination regimens and letrozole alone, the adverse-event entries include multiple dose labels and cross-over groups. The relationship between those labels and the randomized allocation is not fully described.
The record gives a defined response endpoint and assessment schedule, but does not report how missing or unevaluable assessments were handled, whether response assessments were independently reviewed, or how endpoint classification was applied in the uncompleted final analysis. The planned statistical analysis, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record.
Safety counts are also limited by sparse context. The record does not describe the observation period or the detailed procedures for event collection and coding. The percentages listed for serious-event terms lack a stated denominator in the available information, and death counts are null. Cross-over further complicates interpretation of group-level safety counts. These limitations mean that the posted entries support cautious description, not a complete comparative assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Evaluating Temsirolimus (CCI-779) In Breast Neoplasms — NCT00062751.
- Registry record last updated 2011-04-15; status last verified 2011-04.
- Results first posted 2010-11-25.
- 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
This completed Phase 2 study was randomized, open-label, and parallel, with enrollment of 108 participants. It evaluated letrozole alone against letrozole combined with oral temsirolimus regimens in postmenopausal women with locally advanced or metastatic breast cancer. The primary endpoint was the percentage of participants with a confirmed objective response, assessed using specified complete- and partial-response criteria.
The registry states that final efficacy analysis was not conducted because development of temsirolimus for breast cancer was terminated. Primary response estimates and confidence intervals are not reported. The record lists secondary outcomes and descriptive adverse-event counts, including entries related to cross-over, but does not provide enough analysis detail for a complete comparative interpretation.