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 Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer (NCT01132664), a non-randomized phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicity (DLT) - Phase l Only.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01132664 |
| Phase | Phase 1, Phase 2 |
| Condition | Metastatic Breast Cancer, HER2+ Breast Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 72 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with relapsing HER2-overexpressing metastatic breast cancer who had previously failed trastuzumab. The registry describes a general metastatic breast cancer group, with or without PIK3 signaling pathway alteration, and a separate group with brain metastases, also with or without that alteration. The posted record does not give further eligibility details or describe the participants’ baseline characteristics.
Intervention
The study evaluated BKM120 in combination with trastuzumab. Capecitabine is also listed as an intervention, and the study summary describes a BKM120, trastuzumab, and capecitabine combination for patients with brain metastases. Cohort labels identify BKM120 dose levels, but the complete regimen details are not reported in the registry record.
Comparator
There was no randomized comparator. The study was non-randomized, open label, and described as a single-group model. Its dose and disease cohorts therefore do not provide a like-for-like control comparison. Differences across cohorts cannot be interpreted as randomized treatment contrasts.
Primary question
The Phase I primary endpoint was the number of participants with dose-limiting toxicity during Cycle 1, a 28-day period. The registry says this information was used to estimate the probability of dose-limiting toxicity in the dose-determining set when determining the maximum tolerated dose during dose escalation. This is a safety and dose-finding question, not a direct test of comparative efficacy. Numerical primary endpoint results are not reported in the registry record.
3. Trial Design
NCT01132664 is registered as a Phase Ib/II, open-label, multi-center study. Its allocation is non-randomized, its masking is none, and its model is single group. The registry lists enrollment of 72 and identifies metastatic breast cancer and HER2-positive breast cancer as conditions. The study began in 2010-05, had primary completion in 2014-08, and is listed as terminated. The reason for termination is not reported in the registry record.
The study summary describes assessment of BKM120 with trastuzumab in patients with relapsing HER2-overexpressing breast cancer after trastuzumab failure. It also describes preliminary safety and efficacy assessment of BKM120, trastuzumab, and capecitabine in a group with brain metastases. Arm descriptions distinguish a HER2-positive metastatic breast cancer group from a group with brain metastases. Both descriptions include patients with or without PIK3 signaling pathway alteration who had previously failed trastuzumab.
The adverse-event cohort labels list Phase Ib dose escalation at 50 mg/day and 100 mg/day, Phase II dose expansion at 100 mg/day, and brain metastases cohorts at 80 mg/day and 100 mg/day. These labels identify BKM120 dose levels; the complete dosing schedules and cohort assignment rules are not reported in the registry record. Although capecitabine is listed as an intervention, the cohort details do not specify its use or regimen.
Because allocation was not randomized and masking was absent, the study was not designed as a blinded comparison between treatments. The stated Phase I purpose was dose determination based on Cycle 1 toxicity. Secondary outcomes named in the record include disease control rate, clinical benefit rate, and investigator-reviewed progression-free survival. Numerical outcome results and details of the analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Primary outcome measure for BM cohort was MTD/RP2D which was not reached/established due to premature termination of the study. Objective Response Rate (ORR), Disease Control Rate (DCR), Clinical Benefit Rate (CBR) \& Progression Free Survival (PFS)were not calculated for the BM cohort either.
Phase lb
| Stage | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| STARTED | 5 | 12 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 12 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 1 | 2 | 0 | 0 | 0 |
| Disease Progression | 4 | 9 | 0 | 0 | 0 |
Phase ll
| Stage | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 50 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 50 | 0 | 0 |
Reasons for not completing this period:
| Reason | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| Death | 0 | 0 | 2 | 0 | 0 |
| Adverse Event | 0 | 0 | 10 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 3 | 0 | 0 |
| Disease progression | 0 | 0 | 35 | 0 | 0 |
BM Cohort
| Stage | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 3 | 6 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 3 | 6 |
Reasons for not completing this period:
| Reason | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg |
|---|---|---|---|---|---|
| Disease progression | 0 | 0 | 0 | 3 | 4 |
| Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Dose-determining set (DDS) for the determination of the MTD consisted of all patients from the safety set in the dose escalation phase who had met the minimum safety evaluation requirements and the minimum exposure criterion or had experienced DLT during Cycle 1 and were discontinued. MTD analysis was done only on the phase lb group.
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 | Phase Ib - 50 mg | Phase Ib - 100mg | Phase II - 100mg | BM Cohort - 80mg | BM Cohort - 100mg | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 5 | 12 | 42 | 3 | 6 | 68 | |
| Age, Customized: <65 years | Participants | 5 | 11 | 35 | 3 | 6 | 60 |
| Age, Customized: >=65 years | Participants | 0 | 1 | 7 | 0 | 0 | 8 |
| Sex: Female, Male: Female | Participants | 5 | 12 | 42 | 3 | 6 | 68 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Female: Child bearing potential: Able to bear children | Participants | 2 | 3 | 8 | 1 | 1 | 15 |
| Female: Child bearing potential: Premenarche | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Female: Child bearing potential: Post-menopausal | Participants | 3 | 8 | 31 | 2 | 4 | 48 |
| Female: Child bearing potential: Sterile - of child bearing age | Participants | 0 | 1 | 3 | 0 | 1 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Dose Limiting Toxicity (DLT) - Phase l Only, measured over cycle 1 - 28 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled dose-limiting toxicity for Phase I only, with the unit recorded as participants and the parameter as a number. Its timeframe is Cycle 1, defined as 28 days. The registry explains that the probability of dose-limiting toxicity in the dose-determining set was used to determine the maximum tolerated dose in the dose-escalation part of the study. The full operational definition of a dose-limiting toxicity is not reported in the registry record.
In a dose-finding study, observing toxicity during a defined early treatment period helps characterize whether a dose level is tolerable enough to consider for further evaluation. This is a general explanation of the endpoint’s role; it does not establish that a particular dose is safe or effective. The endpoint focuses on participants meeting the study’s dose-limiting toxicity criteria, rather than on every adverse event recorded during the study.
The registry describes the dose-determining set as patients from the safety set in dose escalation who met minimum safety evaluation requirements and minimum exposure criteria, or who experienced dose-limiting toxicity during Cycle 1 and were discontinued. The remaining population description is truncated, and further eligibility or analysis details are not reported in the registry record. No numerical dose-limiting toxicity result is reported, so the endpoint’s observed count and the resulting dose determination cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the study’s design, endpoint description, and adverse-event cohort figures, but it does not report the numerical result for the primary dose-limiting toxicity endpoint. It also does not report numerical results for the named secondary outcomes: disease control rate, clinical benefit rate, or progression-free survival. Consequently, the posted record does not permit an assessment of the observed efficacy outcomes or the precision of any efficacy estimate.
The primary endpoint belongs to the Phase I dose-escalation component. Its purpose was to use Cycle 1 dose-limiting toxicity information to estimate the probability of toxicity in the dose-determining set and inform maximum tolerated dose determination. The endpoint description is not itself a result. Without the dose-limiting toxicity counts, the dose-level estimates, and the dose-selection result, no conclusion about the dose-finding outcome can be drawn from the registry record.
The serious adverse-event figures are presented by cohort and show participants at risk and participants affected. They describe reported safety counts, not randomized contrasts. Cohort sizes differ, and the cohorts represent distinct phases, dose levels, or disease groups. A numerical difference between cohort counts would not isolate a dose effect or treatment effect, because the study did not randomly assign participants to comparable groups. The registry does not report adjusted comparisons to address such differences.
General statistical interpretation: counts are most informative when their denominator, event definition, observation period, and analysis population are clear. The serious-event cohort counts supply some denominators, but the record does not give additional detail on exposure duration or follow-up for those counts. The listed serious-event terms and percentages also lack a stated denominator and fuller definition in the record. They should therefore be read as registry listings, not as a basis for reconstructing participant-level risks.
Terminated is the study status in the registry, but the reason for termination is not reported in the registry record. That status alone does not explain whether the study stopped for safety, feasibility, recruitment, or another reason. Likewise, the enrollment figure is not an outcome count and does not establish how many participants contributed to each endpoint analysis. The analysis populations and endpoint-specific numbers analyzed are not fully reported.
Overall, the record supports a description of the study’s question and structure, but not a conclusion about the magnitude or precision of its primary or efficacy findings. It also cannot establish a comparative treatment effect, since there was no randomized control group. These limits reflect the contents of the registry record rather than an interpretation of unreported trial results.
9. Statistical Methods Explained
The study combines dose escalation and dose expansion within a Phase Ib/II program. The primary outcome is a count of participants with dose-limiting toxicity during Cycle 1. The registry describes using those observations to estimate toxicity probability in the dose-determining set for maximum tolerated dose determination. That makes the Phase I endpoint a dose-finding measure, distinct from the secondary measures of disease control, clinical benefit, and progression-free survival. Numerical results for these outcomes are not reported in the registry record.
What does a count endpoint convey?
A participant count conveys how many people in a defined analysis population experienced an event under the study’s event definition and observation window. It is not interchangeable with a rate unless the denominator and relevant follow-up are also known. In dose escalation, counts at dose levels contribute to an estimate of how likely dose-limiting toxicity is within the chosen assessment period. The registry states this purpose but does not report the counts or estimated probabilities, and the precise dose-limiting toxicity criteria are not reported in the registry record.
The definition of the dose-determining set matters because the estimate depends on who is included. The record says the set included patients from the safety set in dose escalation who satisfied minimum safety evaluation and exposure criteria, or who experienced dose-limiting toxicity and discontinued during Cycle 1. This description indicates that early discontinuation after a dose-limiting toxicity was not automatically excluded. The complete population definition is truncated in the registry record, so further inclusion rules cannot be established.
Why do design features matter?
Non-randomized allocation means participants were not assigned by chance to comparable treatment groups. The listed cohorts vary by study phase, BKM120 dose label, and presence of brain metastases. Those groups may differ in ways related to prognosis, treatment exposure, or event opportunity. General statistical principle: randomization can reduce systematic baseline differences between comparison groups, while an uncontrolled or non-randomized study does not have that protection. Here, cohort comparisons are descriptive and should not be interpreted as randomized treatment contrasts.
Open-label conduct means masking was absent. General statistical principle: knowledge of treatment can influence reporting, assessment, and decisions about whether an outcome has occurred, depending on the outcome and how it is measured. The record identifies investigator assessment for some secondary outcomes, but does not provide enough information to evaluate how assessment procedures were standardized or whether independent review was used beyond the wording of the progression-free survival outcome.
How should efficacy outcomes be read?
Disease control rate and clinical benefit rate are binary-style outcomes in which participants are classified according to whether a defined disease outcome was met. Their interpretation depends on the response criteria, assessment schedule, and analysis population. Those operational details and the numerical results are not reported in the registry record. Progression-free survival is a time-to-event outcome: in general, it concerns the time until progression or death under the specified endpoint definition. The record names investigator review using Kaplan-Meier for this outcome, but does not report the estimate, confidence interval, number of events, or further censoring rules.
General statistical principle: Kaplan-Meier estimation accounts for varying follow-up by using the event and censoring information available over time. Its interpretation depends on the endpoint definition, follow-up, and censoring assumptions. The method name alone does not reveal the estimate or its precision. As the registry does not report the actual progression-free survival analysis results, no numerical inference about that endpoint is possible from the record.
What does a confidence interval add?
General explanation: a confidence interval expresses the statistical uncertainty around an estimate under the analysis method and assumptions used. A narrow interval indicates greater precision than a wide interval, while neither interval alone resolves bias from study design, outcome measurement, or missing data. The registry record does not report confidence intervals for the named outcomes. Therefore, precision cannot be evaluated from the posted results described in the record.
General explanation: for binary outcomes, precision depends in part on the number of participants and the number who experience the event. For time-to-event outcomes, the event information and censoring pattern are important. An enrollment total does not by itself reveal the amount of information available for any particular endpoint, because endpoint-specific populations and events may differ. The record’s enrollment figure should not be treated as an analysis denominator for every outcome.
How do planning illustrations differ from trial design?
The described sample-size framework is a planning illustration based on an observed effect, not the trial’s own design justification. Its assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event outcomes, the framework concerns total events, while other outcomes are expressed as participants per arm. These assumptions describe a hypothetical planning calculation, not the study’s observed power or its actual design. The registry record does not report the study’s own sample-size justification. In addition, this study was non-randomized and single group, so a two-arm equal-allocation illustration does not describe the trial’s actual allocation.
Over-dispersion is a general concern when event counts vary more than a simple statistical model expects. If ignored, uncertainty can be understated and resulting intervals or tests can be misleading. No over-dispersion model or count-based analysis is described in the registry record, and the primary endpoint’s numerical result is not reported. It would therefore be inappropriate to attribute a particular count model or adjustment to this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry names several secondary outcomes: disease control rate, clinical benefit rate, and investigator-reviewed progression-free survival, in addition to the Phase I dose-limiting toxicity endpoint. It does not report a statistical analysis plan describing which outcomes were confirmatory, how they were ordered, or whether any adjustment for multiple testing was planned. The registry record therefore does not establish how the risk of chance findings across multiple outcomes was handled.
The record indicates zero analyses, and it does not provide numerical results for the named primary and secondary outcomes. There are no reported endpoint-specific confidence intervals, p-values, or analysis denominators in the registry record. No claim about statistical significance, multiplicity-adjusted findings, or the hierarchy of outcomes can be made from the available record.
Missing-data methods are not reported in the registry record. The record does not describe how participants with incomplete outcome assessments, early withdrawal, or missing follow-up were handled for disease control, clinical benefit, or progression-free survival. It also does not report outcome-specific missingness or sensitivity analyses. General statistical principle: missing-data handling can affect both the analysis population and the interpretation of estimates, especially when the reasons for missingness are related to participants’ outcomes.
The dose-determining set is partially described for the primary endpoint, but the full description is truncated. The registry does not fully identify analysis populations for the secondary outcomes or state how many participants contributed to each analysis. The enrollment figure is not a substitute for those endpoint-specific populations. As a result, the degree to which analyses included all enrolled participants, or only participants with evaluable data, is not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Phase Ib Dose Escalation 50 mg/Day | 2 | 5 | 40.0% |
| Phase Ib Dose Escalation 100 mg/Day | 2 | 12 | 16.7% |
| Phase II Dose Expansion 100 mg/Day | 17 | 50 | 34.0% |
| BM Cohort 80 mg/Day | 2 | 3 | 66.7% |
| BM Cohort 100 mg/Day | 4 | 6 | 66.7% |
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 |
|---|---|
| Phase Ib Dose Escalation 50 mg/Day | 5 of 5 |
| Phase Ib Dose Escalation 100 mg/Day | 12 of 12 |
| Phase II Dose Expansion 100 mg/Day | 50 of 50 |
| BM Cohort 80 mg/Day | 3 of 3 |
| BM Cohort 100 mg/Day | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase Ib Dose Escalation 50 mg/Day | Phase Ib Dose Escalation 100 mg/Day | Phase II Dose Expansion 100 mg/Day | BM Cohort 80 mg/Day | BM Cohort 100 mg/Day |
|---|---|---|---|---|---|---|
| Asthenia | General disorders | 0 of 5 | 2 of 12 | 3 of 50 | 0 of 3 | 0 of 6 |
| Diarrhoea | Gastrointestinal disorders | 0 of 5 | 1 of 12 | 3 of 50 | 0 of 3 | 0 of 6 |
| Vomiting | Gastrointestinal disorders | 0 of 5 | 0 of 12 | 2 of 50 | 0 of 3 | 0 of 6 |
| Device Related Infection | Infections and infestations | 0 of 5 | 0 of 12 | 2 of 50 | 0 of 3 | 0 of 6 |
| Alanine Aminotransferase Increased | Investigations | 0 of 5 | 0 of 12 | 2 of 50 | 0 of 3 | 0 of 6 |
| Affective Disorder | Psychiatric disorders | 0 of 5 | 1 of 12 | 1 of 50 | 0 of 3 | 0 of 6 |
| Depressed Mood | Psychiatric disorders | 0 of 5 | 1 of 12 | 1 of 50 | 0 of 3 | 0 of 6 |
| Mood Altered | Psychiatric disorders | 0 of 5 | 1 of 12 | 1 of 50 | 0 of 3 | 0 of 6 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 5 | 0 of 12 | 2 of 50 | 0 of 3 | 0 of 6 |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | 0 of 5 | 0 of 12 | 2 of 50 | 0 of 3 | 0 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase Ib Dose Escalation 50 mg/Day | Phase Ib Dose Escalation 100 mg/Day | Phase II Dose Expansion 100 mg/Day | BM Cohort 80 mg/Day | BM Cohort 100 mg/Day |
|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 5 | 5 of 12 | 25 of 50 | 3 of 3 | 5 of 6 |
| Nausea | Gastrointestinal disorders | 2 of 5 | 2 of 12 | 24 of 50 | 2 of 3 | 4 of 6 |
| Decreased Appetite | Metabolism and nutrition disorders | 1 of 5 | 1 of 12 | 18 of 50 | 2 of 3 | 4 of 6 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 5 | 6 of 12 | 16 of 50 | 2 of 3 | 1 of 6 |
| Alanine Aminotransferase Increased | Investigations | 1 of 5 | 4 of 12 | 18 of 50 | 0 of 3 | 1 of 6 |
| Hyperglycaemia | Metabolism and nutrition disorders | 2 of 5 | 5 of 12 | 15 of 50 | 1 of 3 | 1 of 6 |
| Fatigue | General disorders | 0 of 5 | 0 of 12 | 16 of 50 | 3 of 3 | 4 of 6 |
| Aspartate Aminotransferase Increased | Investigations | 1 of 5 | 4 of 12 | 17 of 50 | 0 of 3 | 1 of 6 |
| Vomiting | Gastrointestinal disorders | 2 of 5 | 2 of 12 | 13 of 50 | 1 of 3 | 4 of 6 |
| Cough | Respiratory, thoracic and mediastinal disorders | 0 of 5 | 4 of 12 | 15 of 50 | 2 of 3 | 1 of 6 |
Serious events with the highest arm-level rate: lobar pneumonia (33.3%), sepsis (33.3%), convulsion (33.3%), pneumonitis (33.3%), abdominal pain upper (20.0%).
The serious adverse-event listings are organized by cohort. For each cohort, the record gives the number at risk and the number affected by serious events. The cohort labels are Phase Ib dose escalation at 50 mg/day, Phase Ib dose escalation at 100 mg/day, Phase II dose expansion at 100 mg/day, and brain metastases cohorts at 80 mg/day and 100 mg/day. The affected counts are 2 of 5, 2 of 12, 17 of 50, 2 of 3, and 4 of 6, respectively, using the cohort order just described. These are descriptive cohort counts, not estimates from a randomized comparison.
The record also lists serious-event terms with percentages: Lobar Pneumonia, Sepsis, Convulsion, and Pneumonitis each at 33.3%; Abdominal Pain Upper and Pain each at 20.0%. The denominator and method used for these term percentages are not reported in the registry record. The terms may not represent mutually exclusive participants, so they should not be added or treated as a distribution of all serious events.
Death counts are not reported in the registry record. The displayed cohort counts do not describe event timing, duration of exposure, recurrence, or severity beyond the serious-event classification. These figures document reported safety events; they do not by themselves establish a causal relationship to a study drug.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was intended to evaluate BKM120 with trastuzumab in patients whose HER2-overexpressing breast cancer had relapsed after prior trastuzumab. It also describes an additional brain metastases group and lists capecitabine as part of the intervention set. The Phase I primary endpoint was dose-limiting toxicity during Cycle 1, used to inform maximum tolerated dose determination. These registry entries define the study question and endpoint, but they are not evidence of a particular outcome.
The posted record does not report the numerical dose-limiting toxicity result or the numerical results for the named disease control, clinical benefit, and progression-free survival outcomes. It is therefore not possible to assess their observed magnitude, statistical uncertainty, or consistency across cohorts from this record. The serious-event counts provide safety descriptions for the listed cohorts, but they do not replace the missing primary endpoint result or efficacy estimates.
The study’s non-randomized, single-group design also limits what its data can establish. Without random assignment to a comparable control group, changes or differences cannot be attributed to the study regimen through a randomized treatment contrast. General statistical principle: outcomes observed in a single-group study may reflect the regimen, participant characteristics, prior treatment, disease course, assessment practices, or other influences. The registry record does not report analyses designed to separate these possibilities.
Accordingly, the registry supports a description of the trial’s structure and the event counts it lists, but not a conclusion about comparative benefit or harm. It does not establish whether a treatment works or fails, and the absence of numerical efficacy results in the record should not be interpreted as a null finding. The reason for the terminated status is also not reported, so that status cannot be used to infer why the study ended.
13. Why This Trial Matters Statistically
This study illustrates how a clinical trial can combine an early dose-finding question with later exploratory outcome assessment. The Phase I endpoint is explicitly tied to Cycle 1 dose-limiting toxicity and maximum tolerated dose determination. Disease control, clinical benefit, and progression-free survival address different aspects of disease outcomes, but the registry does not report their numerical results. Keeping those questions distinct helps prevent a safety endpoint from being mistaken for an efficacy result.
It also illustrates why design labels matter when interpreting cohort summaries. The record identifies a non-randomized, open-label, single-group study. Dose levels, study phases, and the presence of brain metastases define groups that are not equivalent to randomized arms. A comparison across those groups can describe the record, but cannot isolate a causal difference between doses or treatment strategies.
The record further shows the difference between an enrollment target or total and an endpoint analysis population. Although enrollment is listed as 72, the number contributing to each outcome is not reported. The dose-determining set is only partly described, while details for secondary analysis populations are absent. Statistical interpretation depends on knowing which participants were analyzed and how incomplete follow-up was handled.
Finally, registry completeness is itself a statistical concern. Without outcome estimates, uncertainty intervals, analysis methods, and the rationale for termination, readers cannot judge the precision or robustness of the primary and secondary findings. Clear reporting of those elements is needed to distinguish a study’s intended question from the evidence its results can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not include numerical results for the primary dose-limiting toxicity endpoint or for the named secondary outcomes. It therefore lacks the estimates needed to assess outcome magnitude and precision. The dose-limiting toxicity definition is not stated, and the population description for the dose-determining set is truncated. These gaps limit interpretation of the principal Phase I question.
The study was non-randomized, open label, and single group. Its cohorts differ by phase, dose label, and brain metastases status, so the adverse-event figures cannot be treated as direct randomized comparisons. The record does not report adjusted analyses addressing baseline differences or other potential sources of confounding. It also does not provide enough detail to assess consistency of assessment across cohorts.
The record lists capecitabine as an intervention and describes a three-drug combination for the brain metastases group, but the complete regimen details are not reported. The reason for termination is not reported in the registry record. Nor does the record fully describe endpoint-specific analysis populations, missing-data procedures, follow-up, or censoring rules. Serious-event term percentages have no stated denominator, and death counts are not reported. These limitations restrict what can be concluded from the registry record, without establishing that unreported information was absent from other study documents.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer — NCT01132664.
- Registry record last updated 2016-08-17; status last verified 2016-08.
- Results first posted 2015-10-30.
- 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
NCT01132664 is a Phase Ib/II, open-label, non-randomized, single-group study listed as terminated. It enrolled 72 participants and evaluated BKM120 with trastuzumab in relapsing HER2-overexpressing breast cancer after trastuzumab failure. The study summary also describes a brain metastases group receiving a regimen that included capecitabine.
The Phase I primary endpoint was the number of participants with dose-limiting toxicity during Cycle 1, a 28-day period, to inform maximum tolerated dose determination. Named secondary outcomes include disease control rate, clinical benefit rate, and investigator-reviewed progression-free survival. The registry record does not report numerical results for these outcomes, the reason for termination, or a complete statistical analysis plan. Safety listings give serious adverse-event counts by cohort, but do not provide a randomized comparison.