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 BKM120 as Second-line Therapy for Advanced Endometrial Cancer (NCT01289041), a na phase 2 study. The primary outcome is Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01289041 |
| Phase | Phase 2 |
| Condition | Advanced Endometrial Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 70 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced endometrial carcinoma whose disease had progressed on or after first-line antineoplastic treatment. The registry describes a full analysis set as patients who received at least one dose of study drug. It also states that tumor tissue, either archival or from a fixed fresh biopsy, was mandatory to assess PI3K pathway activation status.
Intervention
Oral BKM120 at a dose of 100 mg/day. The registry identifies the study as a prospective, multicenter, open-label Phase II investigation of safety and efficacy.
Comparator
There was no separate comparator group. The study is registered as a single-group study with no allocation and no masking. Its results therefore cannot provide a randomized, like-for-like comparison against another treatment or a control condition.
Primary question
The primary endpoint was best overall response rate according to PI3K activation pathway status, assessed over 24 months. The registry describes response as investigator-assessed lesion response using RECIST v1.0. It does not report the response results or the number of participants in each PI3K status category.
In statistical terms, the study asks how often participants receiving BKM120 had a best overall response, and how response related to PI3K pathway activation status. The question is descriptive within the treated study group. Without a separate control group, it does not estimate a treatment contrast against another therapy, usual care, or no treatment.
The registry also lists progression-free survival and overall survival according to PI3K activation pathway status as secondary outcomes. Their results are not reported in the registry record. The record does not specify the detailed definitions of those endpoints, the assessment schedule, or the analyses used to compare status groups. Consequently, those outcome names establish the intended topics of evaluation, but do not establish what was observed or how precisely it was estimated.
3. Trial Design
This was a Phase II, prospective, multicenter, open-label, single-arm study of BKM120 as second-line therapy in advanced endometrial cancer. The registry lists enrollment as 70 and the study status as completed. The listed start is 2011-02, and the listed primary completion is 2014-03. Participants received oral BKM120 at 100 mg/day. The record describes eligibility in relation to disease progression on or after first-line antineoplastic treatment and makes tumor tissue availability mandatory for assessment of PI3K pathway activation status.
The design has a single treated group, rather than separately assigned treatment and control groups. Allocation is listed as not applicable, and masking as none. These features mean the primary response summaries describe outcomes among participants receiving the study drug; they do not estimate a randomized between-group difference. The open-label design also means that investigators knew the treatment being given. The registry states that investigators assessed lesion response, but does not report whether response assessments were independently reviewed or blinded.
Best overall response rate according to PI3K activation pathway status is the primary outcome, with a 24-month timeframe. The record describes the full analysis set as all patients who received at least one dose of study drug. The number in that analysis set is not reported in the registry record, so it should not automatically be equated with the enrollment figure. The listed secondary outcomes are progression-free survival and overall survival according to PI3K activation pathway status.
The registry record does not report a sample-size justification, planned precision target, statistical analysis plan, interim analysis plan, or rules for handling protocol deviations. It also does not report outcome analysis results: the analysis count is recorded as zero. These omissions limit assessment of how the planned design was intended to support inference and whether the registered analysis methods were followed. The design can be described, but conclusions about response, survival, or comparative efficacy cannot be drawn from the design description alone.
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 | All Patients |
|---|---|
| STARTED | 70 |
| COMPLETED | 0 |
| NOT COMPLETED | 70 |
Reasons for not completing this period:
| Reason | All Patients |
|---|---|
| Adverse Event | 24 |
| Physician Decision | 1 |
| Progressive Disease | 41 |
| Withdrawal by Subject | 3 |
| Death | 1 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set includes all patients who received at least one dose of study drug.
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 | All Patients |
|---|---|---|
| Participants analysed | 70 | |
| Age, Continuous | years | 63 (SD 9.04) |
| Sex/Gender, Customized: Female | participants | 70 |
| Sex/Gender, Customized: Male | participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status, measured over 24 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | number of participants |
| Endpoint classification | Binary Endpoint |
Best overall response rate is a binary endpoint: each participant is classified according to whether the best recorded tumor response met the criteria for an overall response. The registry describes the response as an investigator assessment based on RECIST v1.0. For target lesions, complete response means disappearance of all target lesions, while partial response means a >=30% decrease in the sum of the longest diameters of target lesions. The registry defines overall response as complete response plus partial response.
In general, a response-rate endpoint is used to describe the proportion of an assessed group whose tumors meet prespecified response criteria during a stated follow-up period. It reduces measurements taken across assessments to a participant-level response classification, but that simplification does not capture every aspect of disease course. Best overall response rate does not by itself describe how long a response lasted, how quickly progression occurred, or overall survival. Those are distinct questions, and the registry lists progression-free survival and overall survival separately as secondary outcomes.
The primary outcome is specified according to PI3K activation pathway status, which makes the biomarker grouping part of the intended interpretation. However, the registry record does not report the response counts, response-rate estimates, uncertainty intervals, or the numbers assigned to each pathway-status group. The endpoint definition therefore explains what was intended to be measured, not what result was observed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the study as completed and describes its population, intervention, design, and intended outcomes. It does not report an analysis result for the primary response endpoint. In particular, it gives no best overall response count or rate, no estimate by PI3K activation pathway status, and no confidence interval or other measure of uncertainty. A numerical conclusion about the response observed in the study cannot be drawn from the information recorded.
The same distinction applies to the secondary outcomes. Progression-free survival and overall survival according to PI3K activation pathway status are listed, but their estimates and analyses are not reported in the registry record. The outcome names alone do not establish whether either outcome differed across biomarker groups, how long participants were followed, or how complete the follow-up was.
General statistical interpretation: an estimate describes the observed magnitude of an outcome, while a confidence interval describes the range of values reasonably compatible with the data under the method used. A narrow interval generally indicates greater precision than a wide interval. Neither an estimate nor an interval establishes causation by itself. Because the registry record contains no primary response estimate or interval, its precision cannot be evaluated. This is a limit of the available record, not evidence that the response was absent or that an estimate was necessarily imprecise.
The design also constrains what any within-group outcome could establish. With no concurrent control group, an observed response among treated participants would be a description of outcomes under the study conditions. It would not, by itself, separate the effect of BKM120 from the course of disease, participant selection, assessment practices, or other influences. This is why a single-arm result should not be read as a randomized comparison or as a direct estimate of what would have happened to the same population under another treatment.
Interpretation by PI3K activation status would require additional information. The record says that tissue assessment was mandatory and that outcomes were to be considered according to pathway status, but it does not give the classification method, group sizes, response results by group, or a statistical comparison. Without these details, it is not possible to judge the magnitude or precision of any association between pathway status and response. Nor can the record show whether a status-based analysis was prespecified or exploratory.
The adverse-event entries are descriptive safety data, not a substitute for the missing efficacy results. The registry lists 33 participants with serious adverse events among 70 at risk and 67 with other adverse events among 70 at risk. It also lists several serious adverse-event terms with percentages. These entries describe reported events in the study group; they do not establish a comparative excess or a causal effect, because there is no comparator group. The death count is not reported in the registry record.
Overall, the registered design and endpoint definitions explain what the trial intended to study, while the recorded analysis information is insufficient to quantify the primary outcome or its uncertainty. Statistical conclusions should therefore remain limited to the design description and the adverse-event entries actually reported. Absence of an analysis result in the registry record should not be converted into a claim of benefit, lack of benefit, or no response.
9. Statistical Methods Explained
The registered study design is single-arm and open-label. In a single-arm study, outcome measures are summarized for participants receiving the intervention rather than contrasted with an internally assigned control group. This can be useful for describing outcomes in a defined study population, but it does not provide the same protection against confounding as randomized allocation. The registry records allocation as not applicable and masking as none. It does not report a formal statistical analysis plan or the methods used for any outcome analysis.
What does a binary response measure?
General explanation: a binary outcome places each participant into one of two categories, such as meeting or not meeting a response definition. A response rate is an estimate based on the number classified as responders relative to the relevant analysis group. Its interpretation depends on the response criteria, the population included, and how missing or unevaluable assessments are handled. In this study, the registry identifies best overall response rate as the primary outcome and defines response using investigator-assessed RECIST v1.0 criteria. It does not report the response numerator or estimate, so no response rate can be interpreted from the registry record.
Best overall response reduces assessments over time to the best qualifying response recorded for a participant. That summary can describe whether a response was observed, but it does not represent response duration. It also does not answer survival questions, which the registry lists separately. The stated timeframe is 24 months, but the registry does not provide assessment schedules, censoring rules, or information about the duration of observation for each participant.
How should uncertainty be read?
General explanation: a confidence interval expresses uncertainty around an estimated quantity under specified statistical assumptions. It helps distinguish an estimate that is relatively precise from one compatible with a broad range of values. A confidence interval is not a guarantee that the true value lies within its endpoints, and its meaning depends on the analysis method and data quality. No confidence interval for best overall response or the secondary outcomes is reported in the registry record. The uncertainty of those outcomes is therefore not assessable from the registered information.
For a single-arm response estimate, uncertainty would ordinarily reflect the number of participants contributing to the endpoint and the observed response pattern. Interpretation would also depend on the definition of the analysis population and the handling of missing response assessments. The record defines the full analysis set as participants who received at least one dose, but does not give its size or state how missing or unevaluable response data were treated. Enrollment is listed as 70; that entry does not establish the size of every endpoint-specific analysis group.
What does the biomarker grouping add?
The primary outcome is titled according to PI3K activation pathway status, and the brief study description says tumor tissue was required for assessment of pathway activation. A status-based summary could describe response separately across biomarker groups. General explanation: such subgroup summaries are often less precise than a whole-group estimate because each subgroup contains fewer observations, and comparisons across subgroups can be sensitive to how the groups were defined. No status classification rules, subgroup sizes, response estimates, or subgroup comparison methods are reported in the registry record. It is therefore not possible to assess the statistical precision or strength of any association between pathway status and response.
How do survival outcomes differ?
General explanation: progression-free survival and overall survival are time-to-event outcomes. Their analysis typically needs definitions of the event, follow-up time, censoring, and the methods used to estimate or compare event-time distributions. These outcomes answer different questions from a binary response endpoint. The registry lists progression-free survival and overall survival according to PI3K activation pathway status as secondary outcomes, but does not report their estimates, events, follow-up summaries, or analysis methods. No survival conclusion can be recovered from the outcome titles alone.
What can be inferred from the analysis record?
The registry lists zero analyses. This means the record does not contain reported outcome analyses to interpret. It does not establish whether analyses were conducted outside the registry or whether a separate report exists; those details are not reported in the registry record. The statistical analysis plan, model choices, adjustment methods, treatment of protocol deviations, and interim analysis plans are also not reported in the registry record.
The record includes general planning assumptions for illustrations based on an observed effect, but does not include the illustration values or an observed primary effect in the registry record for interpretation. Any such planning illustration should be distinguished from the original trial design and from actual observed precision. A sample-size calculation is a planning tool that describes what a hypothetical design might require under stated assumptions; it is not an observed treatment effect and is not observed power. The registry does not report the trial's own sample-size justification, so the planning assumptions cannot be treated as the study's prespecified design rationale.
Finally, the event summaries are counts, not comparative effect estimates. General explanation: over-dispersion is extra variation beyond that allowed by a chosen statistical model and can make standard errors too small if ignored. It is relevant to some count-data analyses, but the registry does not report a count model or a comparative analysis of adverse events. The safety figures should therefore be read descriptively rather than as model-based comparisons.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is best overall response rate according to PI3K activation pathway status. The registry also lists progression-free survival and overall survival according to that status as secondary outcomes. Considering several outcomes or several subgroup comparisons can raise a multiplicity question: when many hypotheses are tested, the chance of at least one apparently noteworthy result can increase. General statistical practice may address this through prespecified outcome hierarchies, adjusted testing procedures, or clear separation of confirmatory and exploratory analyses.
The registry record does not report a multiplicity strategy, a hierarchy of tests, or whether the status-based comparisons were confirmatory or exploratory. It also records zero analyses, so there are no reported test results to assess for multiplicity. It would be inappropriate to assume that an adjustment was or was not used in analyses conducted outside the registry record.
The full analysis set is described as all patients who received at least one dose of study drug. Its size is not reported in the registry record. The record does not state how participants with missing tissue, unevaluable response, withdrawal, or incomplete follow-up were handled in the endpoint analyses. Although tumor specimen availability is described as mandatory, the number with usable tissue and the handling of any unavailable or unclassifiable status are not reported in the registry record. Missing-data assumptions and sensitivity analyses are also not reported.
These omissions matter because outcome estimates can depend on which participants are included and how unavailable assessments are treated. The enrollment figure alone cannot establish the analysis denominator for the primary endpoint or either secondary outcome. Without denominators, missing-data rules, and analysis results, readers cannot evaluate whether the reported population matched the intended analysis set or how robust the results were to missing information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Patients | 33 | 70 | 47.1% |
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 |
|---|---|
| All Patients | 67 of 70 |
Most frequent serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Dehydration | Metabolism and nutrition disorders | 4 of 70 |
| Hyperglycaemia | Metabolism and nutrition disorders | 4 of 70 |
| Vomiting | Gastrointestinal disorders | 3 of 70 |
| Hypersensitivity | Immune system disorders | 3 of 70 |
| Hydronephrosis | Renal and urinary disorders | 3 of 70 |
| Abdominal pain | Gastrointestinal disorders | 2 of 70 |
| Nausea | Gastrointestinal disorders | 2 of 70 |
| Stomatitis | Gastrointestinal disorders | 2 of 70 |
| Asthenia | General disorders | 2 of 70 |
| Sepsis | Infections and infestations | 2 of 70 |
Most frequent non-serious adverse event terms
| Event term | Organ system | All Patients |
|---|---|---|
| Hyperglycaemia | Metabolism and nutrition disorders | 37 of 70 |
| Nausea | Gastrointestinal disorders | 31 of 70 |
| Decreased appetite | Metabolism and nutrition disorders | 28 of 70 |
| Fatigue | General disorders | 24 of 70 |
| Rash | Skin and subcutaneous tissue disorders | 21 of 70 |
| Aspartate aminotransferase increased | Investigations | 18 of 70 |
| Diarrhoea | Gastrointestinal disorders | 17 of 70 |
| Alanine aminotransferase increased | Investigations | 17 of 70 |
| Anxiety | Psychiatric disorders | 17 of 70 |
| Depression | Psychiatric disorders | 16 of 70 |
Serious events with the highest arm-level rate: dehydration (5.7%), hyperglycaemia (5.7%), vomiting (4.3%), hypersensitivity (4.3%), hydronephrosis (4.3%).
The registry lists a single group, All Patients, with 70 at risk for serious adverse events and 33 affected. It also lists 70 at risk for other adverse events and 67 affected. These are separate event summaries; the record does not say whether the same participants appear in both categories. The number of deaths is not reported in the registry record.
The listed serious adverse-event terms and percentages are dehydration, 5.7%; hyperglycaemia, 5.7%; vomiting, 4.3%; hypersensitivity, 4.3%; hydronephrosis, 4.3%; and abdominal pain, 2.9%. These are the entries recorded for the listed terms. The record does not describe how events were attributed to treatment, how severity was graded, or whether the term percentages refer to participants or event occurrences. They should not be converted into counts or treated as estimates of comparative risk.
General explanation: adverse-event summaries are descriptive unless a suitable comparison and analysis are available. In a single-arm study, these counts can indicate what was recorded among participants in the treated group, but they cannot show how event frequency compares with another treatment or with the background rate in a similar population. The registry record does not provide such a comparator. The safety entries should therefore be read as reported study-group observations, not as proof that BKM120 caused or prevented a particular event.
12. What the Result Does, and Does Not, Mean
The record supports a description of the study's purpose and structure: a completed, open-label, single-arm Phase II investigation of oral BKM120 in advanced endometrial cancer after first-line antineoplastic treatment. Its primary outcome was best overall response rate according to PI3K activation pathway status, assessed using investigator-assessed RECIST v1.0 criteria over 24 months. The record also identifies progression-free survival and overall survival by pathway status as secondary outcomes.
It does not provide the outcome analyses needed to say what response rate was observed, how response varied by pathway status, or how precisely any estimate was measured. It also does not report the secondary survival results. Therefore, the registered information does not support a claim that the intervention improved outcomes, failed to improve outcomes, or produced no responses. Those conclusions require outcome estimates and an appropriate interpretation of their uncertainty.
The single-arm design is important to the scope of inference. Even if a within-group response estimate were available, it would describe participants receiving the study treatment under the study conditions. Without a concurrent randomized comparator, that estimate alone would not establish what would have occurred under another treatment or identify the treatment's causal effect. The registry record does not report a control group or a comparative analysis.
The adverse-event entries do show that serious and other adverse events were recorded among participants in the study group, along with selected serious-event terms and percentages. They are not comparative risk estimates, and the record does not provide a death count. Reading these entries alongside the missing efficacy analyses does not resolve the unanswered efficacy questions. The most defensible interpretation is that the registry documents the design, intended endpoints, and selected safety summaries, while the primary and secondary outcome results and their precision are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates a common statistical distinction between a clearly defined research question and a reportable result. The registry identifies a population, intervention, response endpoint, timeframe, and biomarker grouping. Those details allow readers to understand what the investigators intended to assess. But without outcome estimates and uncertainty measures, the statistical evidence about the primary question cannot be evaluated from the registry record.
The single-arm design also makes the target of inference especially important. A response summary within a treated group is not a randomized treatment contrast. Statistical interpretation must keep descriptive evidence separate from causal evidence, even when an outcome is clinically meaningful and the eligibility criteria are specific. The lack of a comparator is not a flaw that can be repaired by rephrasing a within-group estimate; it defines what the design can answer.
The biomarker component adds a further interpretive layer. The primary outcome is framed according to PI3K activation pathway status, and the registry makes tissue assessment central to the study description. Yet the record does not provide status definitions, subgroup sizes, or outcome estimates by status. This highlights why subgroup questions require clear classification methods and adequate reporting of denominators and uncertainty, rather than only naming a biomarker in an endpoint.
Safety reporting also demonstrates the difference between event counts and comparative evidence. The recorded counts and selected term percentages describe events in the study group, but cannot establish relative risk without a comparison and suitable analysis. Taken together, these features make the study statistically informative as an example of how design, endpoint definition, analysis population, and reporting completeness jointly determine the conclusions readers can draw.
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 direct limitation of the registry information is that it contains no outcome analyses. Although the record identifies best overall response rate as the primary endpoint and lists two secondary survival outcomes, it does not report their results, estimates, or uncertainty. Consequently, readers cannot quantify the primary outcome or assess its precision, and cannot interpret the secondary outcomes.
The single-arm, open-label design limits causal and comparative interpretation. There is no separate control group, and investigator-assessed response is described without information about independent review or blinded assessment. The record does not report how response assessment timing, missing assessments, or unevaluable cases were handled. It defines the full analysis set as participants receiving at least one dose, but does not provide that set's size.
PI3K pathway status is central to the primary outcome, but the record does not provide the status classification method, subgroup denominators, or subgroup results. Mandatory tissue availability is stated, but the number of participants with evaluable tissue and the handling of missing or indeterminate status are not reported in the registry record. The registry also does not report details of survival follow-up, censoring, or event definitions.
Safety interpretation is limited by the absence of a comparator and by missing detail on event attribution, grading, and the denominator convention for the listed term percentages. The death count is not reported in the registry record. The statistical analysis plan, multiplicity handling, interim analyses, and sample-size justification are also not reported in the registry record. These gaps do not establish that such procedures were absent from all study documentation, but they prevent assessment from the registry entry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: BKM120 as Second-line Therapy for Advanced Endometrial Cancer — NCT01289041.
- Registry record last updated 2019-05-30; status last verified 2019-05.
- Results first posted 2015-04-10.
- 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
The registry identifies NCT01289041 as a completed Phase II, prospective, multicenter, open-label, single-arm study of oral BKM120 at 100 mg/day. The population was patients with advanced endometrial carcinoma whose disease progressed on or after first-line antineoplastic treatment. Enrollment is listed as 70.
The primary outcome was best overall response rate according to PI3K activation pathway status, based on investigator-assessed RECIST v1.0 response over 24 months. Progression-free survival and overall survival according to pathway status were listed as secondary outcomes. The registry describes the full analysis set as patients who received at least one dose.
The record lists 33 participants with serious adverse events and 67 with other adverse events, each among 70 at risk, plus selected serious-event terms and percentages. It records zero analyses; primary and secondary outcome results, statistical methods, and several analysis details are not reported in the registry record.