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 of Prophylactic Octreotide to Prevent or Reduce the Frequency and Severity of Diarrhoea in Subjects Receiving Lapatinib With Capecitabine for the Treatment of Metastatic Breast Cancer (NCT02294786), a randomized phase 2 study. The primary outcome is Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02294786 |
| Phase | Phase 2 |
| Condition | Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 62 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants had HER2-positive metastatic breast cancer that had progressed after prior therapy. The prior therapy was required to include anthracyclines and taxanes, as well as trastuzumab in the metastatic setting. The registry record reports 62 participants enrolled.
Intervention
The intervention was prophylactic octreotide added to lapatinib and capecitabine. The arm description states that octreotide was given as Sandostatin LAR™ 40mg 7 days before starting the other treatments and again 28 days later.
Comparator
The comparator was lapatinib and capecitabine without octreotide. The study was not placebo controlled and had no active comparator beyond the no-octreotide arm. The arm descriptions state that participants in this group began lapatinib and capecitabine immediately following enrolment.
Primary question
The primary outcome was the proportion of participants experiencing at least one episode of Grade 2 or higher diarrhoea up to 24 weeks. The clinical question was whether adding prophylactic octreotide would prevent or reduce the frequency and severity of diarrhoea associated with lapatinib and capecitabine. The registry record does not report a single primary-outcome comparison or its result.
The study addressed treatment-associated diarrhoea, which the registry summary describes as commonly reported with lapatinib and capecitabine. Its stated rationale was that diarrhoea can affect tolerability and, in severe cases, may lead to poor compliance or treatment interruption or withdrawal. Those statements describe the rationale for studying prevention; they do not establish what happened in this trial.
The comparison is an add-on question: both arms received the cancer treatments, while octreotide differed between arms. Because there was no placebo, treatment assignment was open label. The registered clinical question therefore concerns octreotide as prophylaxis against diarrhoea, not a comparison between cancer-treatment regimens.
3. Trial Design
This was a randomized, multicentre, open-label, parallel-group Phase II study. The registry lists cancer as the condition and Novartis Pharmaceuticals as the sponsor. The study start date was 2014-12-17, and the primary completion date was 2017-10-19. Its status is recorded as terminated. The reason for termination is not reported in the registry record.
Participants were assigned to octreotide treatment or no octreotide treatment. Both groups received lapatinib and capecitabine. The registry summary says the study was not placebo controlled and had no active comparator. The arm descriptions indicate that octreotide was given before and during the initial period of cancer treatment; the full dosing details for lapatinib and capecitabine are not reported in the registry record.
The registry reports enrollment of 62 participants. The brief summary states that approximately 140 participants were planned to be randomized, but its description of the planned enrollment is truncated. The reason actual enrollment was lower than the stated plan is not reported in the registry record. The enrollment count alone does not establish how many participants completed follow-up or contributed data to each outcome.
Study completion for an individual participant was defined as completing 24 weeks of lapatinib and capecitabine treatment, or having cancer progression or dying during treatment, whichever occurred first. This definition sets the intended observation period but does not describe the amount of follow-up actually available for every participant. Further detail about randomization procedures, allocation concealment, stratification, and the statistical plan is not reported in the registry record.
The registry lists 20 outcome measures and one analysis. The primary outcome is specified as a participant count for diarrhoea of Grade 2 or higher up to 24 weeks. However, the registry record does not provide a single result for a primary comparison between the randomized groups.
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: The study was terminated early after 62 patients (out of 140 planned) were randomized as criteria for futility was met.
Overall Study
| Stage | Octreotide Treatment | No Octreotide Treatment |
|---|---|---|
| STARTED | 30 | 32 |
| Safety Population | 29 | 33 |
| ITT Population | 30 | 32 |
| COMPLETED | 19 | 18 |
| NOT COMPLETED | 11 | 14 |
Reasons for not completing this period:
| Reason | Octreotide Treatment | No Octreotide Treatment |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
| Physician Decision | 6 | 7 |
| Lost to Follow-up | 1 | 2 |
| Protocol Violation | 1 | 0 |
| Adverse Event | 1 | 1 |
| Death | 2 | 3 |
Analysis population for the primary outcome, as defined in the registry: ITT - For cycle 1-3 analysis: Subjects that withdrew from the study on or prior to the Cycle 4 visit date were assumed to have experienced diarrhoea. For the cycle 1-8 analysis: Subjects who did not have diarrhea event prior to the End of Study/Withdrawal visit date were not assumed to have experienced diarrhoea.
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 | Octreotide Treatment | No Octreotide Treatment | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 32 | 62 | |
| Age, Continuous | Years | 57.4 (SD 10.07) | 55.9 (SD 9.08) | 56.6 (SD 9.52) |
| Sex: Female, Male: Female | Participants | 30 | 32 | 62 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 30 | 31 | 61 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Subjects Experiencing Diarrhoea of Grade 2 and Above (up to 24 Weeks), measured over Up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns the proportion of participants who experienced at least one episode of diarrhoea of Grade 2 or higher up to 24 weeks. The registry describes this as an adverse event recorded in the electronic case report form and graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. The endpoint is therefore a participant-level event measure: it asks whether a participant had at least one qualifying episode during the specified period, rather than counting every episode.
As a general statistical concept, setting a severity threshold distinguishes events meeting a specified grade from events below that threshold. A participant-level measure can be easier to interpret than a total episode count when the question is whether participants experienced the event at all. It does not, by itself, describe how many episodes each participant had, how long episodes lasted, or when they began. The registry lists separate outcomes for diarrhoea of any grade, duration, time to first episode, and related treatment or healthcare use.
The outcome definition identifies a follow-up window and a grading system, but does not provide a single between-group estimate, confidence interval, or test result. Those results are not reported in the registry record. The endpoint’s stated definition can therefore be described, but the registry information does not support a numerical conclusion about the randomized comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the study question and design but does not reduce the primary endpoint to one comparison between octreotide and no octreotide. It provides no primary-outcome group counts, effect estimate, confidence interval, or p-value for a single comparison. Consequently, the magnitude and precision of any difference in Grade 2 or higher diarrhoea cannot be assessed from the registry record.
The record identifies a primary outcome measured up to 24 weeks and describes an analysis population that includes assumptions about diarrhoea events for some participants. Those rules matter because the handling of withdrawals can affect the event counts used in an analysis. They do not supply the missing group-specific counts or an estimate of the contrast between groups. The detailed population description is truncated, and further missing-data procedures are not reported in the registry record.
Enrollment was 62, while the brief summary refers to approximately 140 planned participants. This indicates that the observed enrollment did not reach the stated approximate plan; it does not by itself show the reason, the number analyzed for the primary endpoint, or the effect on the result. The termination reason and any study-level explanation are not reported in the registry record. It would not be appropriate to infer that termination was caused by efficacy, safety, recruitment, or any other particular factor.
Safety information is reported separately. The serious-adverse-event figures include 5 affected participants among 29 at risk in the octreotide group and 3 among 33 at risk in the no-octreotide group. The record also reports other adverse events affecting 26 of 29 and 27 of 33 participants, respectively. These are descriptive counts; the registry record does not report a statistical comparison or establish that an event was caused by treatment. Deaths are recorded as 1 in the octreotide group and 0 in the no-octreotide group, without a reported attribution to treatment.
Overall, the posted information permits description of the trial framework and some safety counts, but not a conclusion about the primary efficacy comparison. A confidence interval, when reported, would describe the uncertainty around an estimated effect; no such interval for the primary comparison is reported in the registry record. The absence of a reported result should not be interpreted as evidence that the groups were the same or different.
9. Statistical Methods Explained
The study used a randomized, parallel-group design. In general, randomization is intended to create groups whose baseline characteristics are comparable on average, so that differences in outcomes can be interpreted in relation to the assigned intervention, subject to adherence, follow-up, and analysis choices. The registry identifies the study as randomized but does not report the randomization sequence method, allocation concealment, or any stratification factors. Open-label means that the study was not masked; placebo control was absent.
What does the primary endpoint count?
The endpoint is the number or proportion of participants who experienced at least one episode of Grade 2 or higher diarrhoea during follow-up up to 24 weeks. It is not an episode rate. A participant with multiple qualifying episodes still meets the participant-level definition. In general, binary outcomes such as whether an event occurred can be summarized with counts and proportions in each group, and a comparison may express the difference or ratio between those group summaries. No single primary comparison or its numerical result is reported in the registry record, so no such effect should be inferred.
The endpoint specifies NCI CTCAE version 4.03 and eCRF recording. These define the grading reference and data source described in the registry. The registry does not report additional details about how episodes were adjudicated, whether outcome assessors were independent, or how disagreements in grading were resolved.
How should an estimate and its uncertainty be read?
As a general statistical concept, an effect estimate describes the observed contrast between groups for a defined outcome. A confidence interval describes uncertainty around that estimate under the assumptions of the analysis. A narrow interval indicates more precision than a wide interval, while an interval spanning values compatible with materially different effects can leave the size and direction uncertain. The registry record does not report a primary effect estimate or confidence interval, so the precision of the primary comparison cannot be evaluated.
A p-value, when reported, measures how compatible the data are with a specified null hypothesis under the chosen statistical model. It does not measure the probability that the null hypothesis is true, and it does not indicate the clinical importance of an effect. No primary-comparison p-value is reported in the registry record. The significance level and test used for the primary endpoint are also not reported in the registry record.
Why do analysis populations and follow-up rules matter?
The primary outcome description refers to an ITT population and contains specific assumptions about participants who withdrew. For the cycle 1-3 analysis, participants who withdrew on or before the Cycle 4 visit date were assumed to have experienced diarrhoea. For the cycle 1-8 analysis, participants without a diarrhoea event before the End of Study/Withdrawal visit date were not assumed to have experienced one. These rules show that the treatment of incomplete follow-up was tied to the analysis period. The population description is truncated, so the complete rules and their application cannot be determined from the registry record.
In general, missing outcomes can affect a binary event estimate when participants have different amounts of observation or when withdrawal is related to the outcome. An assumption that a withdrawn participant experienced an event differs from assuming that the event did not occur. The suitability of either assumption depends on the analysis context and the unobserved outcomes. Further sensitivity analyses or alternative missing-data methods are not reported in the registry record.
What can be inferred from the safety counts?
Safety counts describe participants recorded with events in the registry’s adverse-event groups. They are not automatically estimates of causal treatment effects. In general, a comparative safety analysis would need a defined event window, consistent ascertainment, and an appropriate analysis of the group contrast. The registry record reports participant counts at risk and affected, but does not report a statistical comparison for these figures. It also does not state whether the listed events were judged treatment-related.
The registry lists 20 outcome measures but only one analysis. That count does not identify which outcomes were included in the analysis, whether outcome-specific comparisons were prespecified, or how the analysis addressed multiple outcomes. Details of the statistical model, covariates, handling of repeated observations, and adjustment for multiplicity are not reported in the registry record.
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such sample-size illustrations are planning exercises, not observed power. The illustration’s outcome-specific sample-size values are not included in the record details, and the trial’s own sample-size justification is not reported in the registry record. No recalculated primary effect is available to interpret.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 20 outcome measures, including the primary Grade 2 or higher diarrhoea outcome and secondary measures covering severe diarrhoea, diarrhoea of any grade, duration, time to onset, medication use, unscheduled healthcare visits, and dose changes. When several outcomes or time points are examined, the chance of at least one apparently notable result can increase if each is tested separately. As a general statistical approach, a study may specify a hierarchy or multiplicity adjustment, but such a plan is not reported in the registry record.
The record lists one analysis, but that count does not establish how many outcome comparisons were made or whether any adjustment was used. The primary outcome is identified, yet no single comparison is reported. The complete statistical analysis plan, including any planned handling of multiple outcomes or time points, is not reported in the registry record.
The primary outcome description refers to an ITT population and gives different assumptions about event status for withdrawals in the cycle 1-3 and cycle 1-8 analyses. The description is truncated, so the full analysis-population definition and all missing-data rules are not reported in the registry record. The record does not report sensitivity analyses assessing alternative assumptions for missing outcomes, or the numbers of participants with observed primary-outcome data in each group.
These omissions limit the ability to assess the robustness of an outcome comparison, even apart from the absence of a single primary result. No inference about how missing data or multiplicity changed the results is possible from 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 |
|---|---|---|---|
| Octreotide Treatment | 5 | 29 | 17.2% |
| No Octreotide Treatment | 3 | 33 | 9.1% |
| All Patients | 8 | 62 | 12.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Octreotide Treatment | 1 of 29 |
| No Octreotide Treatment | 0 of 33 |
| All Patients | 1 of 62 |
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 |
|---|---|
| Octreotide Treatment | 26 of 29 |
| No Octreotide Treatment | 27 of 33 |
| All Patients | 53 of 62 |
Most frequent serious adverse event terms
| Event term | Organ system | Octreotide Treatment | No Octreotide Treatment | All Patients |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 29 | 0 of 33 | 1 of 62 |
| Lower respiratory tract infection | Infections and infestations | 1 of 29 | 0 of 33 | 1 of 62 |
| Vulvitis | Infections and infestations | 1 of 29 | 0 of 33 | 1 of 62 |
| Alanine aminotransferase increased | Investigations | 1 of 29 | 0 of 33 | 1 of 62 |
| Osteonecrosis of jaw | Musculoskeletal and connective tissue disorders | 0 of 29 | 1 of 33 | 1 of 62 |
| Paraparesis | Nervous system disorders | 0 of 29 | 1 of 33 | 1 of 62 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 0 of 29 | 1 of 33 | 1 of 62 |
| Thrombosis | Vascular disorders | 1 of 29 | 0 of 33 | 1 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Octreotide Treatment | No Octreotide Treatment | All Patients |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 17 of 29 | 15 of 33 | 32 of 62 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 13 of 29 | 11 of 33 | 24 of 62 |
| Rash | Skin and subcutaneous tissue disorders | 4 of 29 | 7 of 33 | 11 of 62 |
| Asthenia | General disorders | 2 of 29 | 7 of 33 | 9 of 62 |
| Anaemia | Blood and lymphatic system disorders | 1 of 29 | 6 of 33 | 7 of 62 |
| Blood bilirubin increased | Investigations | 4 of 29 | 3 of 33 | 7 of 62 |
| Thrombocytopenia | Blood and lymphatic system disorders | 3 of 29 | 3 of 33 | 6 of 62 |
| Alanine aminotransferase increased | Investigations | 4 of 29 | 2 of 33 | 6 of 62 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 29 | 4 of 33 | 5 of 62 |
| Aspartate aminotransferase increased | Investigations | 4 of 29 | 1 of 33 | 5 of 62 |
Serious events with the highest arm-level rate: diarrhoea (3.4%), lower respiratory tract infection (3.4%), vulvitis (3.4%), alanine aminotransferase increased (3.4%), thrombosis (3.4%).
The registry reports serious adverse events for 29 participants at risk in the octreotide group, with 5 participants affected, and for 33 at risk in the no-octreotide group, with 3 affected. For other adverse events, it reports 26 affected among 29 at risk in the octreotide group and 27 among 33 at risk in the no-octreotide group. These are descriptive participant counts, not adjusted comparisons. The registry record does not report a statistical test or confidence interval for these group figures.
The all-patients entry reports 8 participants with serious adverse events among 62 at risk and 53 with other adverse events among 62 at risk. Deaths are recorded as 1 in the octreotide group and 0 in the no-octreotide group. The registry does not state that these deaths were caused by study treatment, and the count alone cannot establish attribution.
Among the listed serious-event terms, diarrhoea, lower respiratory tract infection, vulvitis, alanine aminotransferase increased, and thrombosis are each shown as 3.4%; osteonecrosis of jaw is shown as 3.0%. These term percentages should be read as registry-reported values. The record does not provide enough detail to infer a comparative risk for each term or determine whether an event was judged related to a particular treatment. Adverse-event counts describe what was recorded; they do not by themselves establish causality.
12. What the Result Does, and Does Not, Mean
The study’s intended comparison was prophylactic octreotide plus lapatinib and capecitabine versus lapatinib and capecitabine without octreotide. Its primary outcome was Grade 2 or higher diarrhoea up to 24 weeks. The registry record describes that question but does not report a single primary-outcome comparison, group-specific primary counts, or an effect estimate. It therefore does not establish the size or precision of a difference between the randomized groups.
The safety information provides descriptive counts of participants with serious and other adverse events, along with deaths and selected serious-event terms. These data are not presented as a comparative statistical analysis. They cannot, on their own, establish that octreotide caused or prevented an event, and the registry does not report attribution for the deaths.
The record’s terminated status and enrollment of 62 participants are relevant context, but they do not explain why the study ended or what the unreported primary comparison would have shown. The brief summary states that approximately 140 participants were planned. The reason for the difference between planned and actual enrollment is not reported in the registry record. No conclusion about the study’s result should be inferred from termination or enrollment alone.
In general, a trial result is best interpreted using an effect estimate, its uncertainty, the outcome definition, and the analysis population. Here, the outcome definition and some population rules are described, but the primary estimate and its uncertainty are absent. The appropriate reading is therefore limited: the registry documents the clinical question and selected safety information, but does not provide a numerical primary-outcome result from which to judge the comparative effect.
This distinction is important. A missing result is not evidence that there was no effect, nor is it evidence that there was an effect. It leaves the primary comparison unresolved in the registry record.
13. Why This Trial Matters Statistically
This trial raises several statistical issues that are common in studies of treatment-associated adverse events. The endpoint is a participant-level binary outcome over a defined follow-up period, while other registered outcomes address severity, duration, onset, and consequences such as medication use or dose changes. These outcomes describe different features of diarrhoea and should not be treated as interchangeable.
Follow-up and withdrawal rules are particularly relevant when an outcome can occur at any point during treatment. The registry’s assumptions for withdrawn participants differ across the cycle 1-3 and cycle 1-8 descriptions. Such rules can affect who is counted as having experienced an event, making a clear analysis-population definition essential. The registry description is truncated, and the full statistical approach is not reported.
The study also illustrates why descriptive safety counts and an efficacy comparison answer different questions. Counts of affected participants can summarize recorded events, while a randomized comparison requires a defined outcome analysis and an estimate of the contrast between groups. The record contains safety counts but does not report a single primary-outcome comparison or a statistical comparison for the safety figures.
Finally, the study’s terminated status and enrollment below the stated approximate plan make the completeness of the reported results important context, but do not explain the study’s course or establish an outcome. The termination reason and the trial’s own sample-size justification are not reported in the registry record. Without the primary estimate and its uncertainty, readers cannot determine what range of effects is compatible with the trial’s data. The statistical importance lies both in the design choices documented and in the limits of what the registry record allows readers to conclude.
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 main limitation for interpreting the clinical question is that the registry record does not report a single primary-outcome comparison. It identifies the endpoint and follow-up window but does not provide primary group counts, an effect estimate, a confidence interval, or a p-value. The clinical effect and its precision therefore cannot be assessed from this record.
The outcome-population description is truncated. It includes rules for withdrawals in the cycle 1-3 and cycle 1-8 analyses, but does not give the complete definition or all associated analysis details. The registry record does not report the number of participants contributing primary-outcome data in each group or sensitivity analyses for missing outcomes.
Although the study is described as randomized, multicentre, open label, and parallel group, details of sequence generation, allocation concealment, stratification, and outcome assessment are not reported in the registry record. The open-label design and lack of placebo are recorded features; the registry does not provide information that would allow assessment of how awareness of assignment affected event reporting or management.
The registry lists 20 outcome measures and one analysis, but does not report a complete statistical analysis plan or describe any multiplicity approach. The reason for termination is not reported. The record states enrollment of 62 and approximately 140 planned participants, but does not explain the enrollment shortfall or provide the trial’s own sample-size justification. These omissions limit interpretation of both the intended analysis and the completeness of the evidence available in the registry.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Prophylactic Octreotide to Prevent or Reduce the Frequency and Severity of Diarrhoea in Subjects Receiving Lapatinib With Capecitabine for the Treatment of Metastatic Breast Cancer — NCT02294786.
- Registry record last updated 2019-07-15; status last verified 2019-05.
- Results first posted 2019-07-15.
- 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
NCT02294786 was a randomized, open-label, parallel-group Phase II study of prophylactic octreotide with lapatinib and capecitabine in HER2-positive metastatic breast cancer. The comparator group received lapatinib and capecitabine without octreotide. The primary endpoint was the proportion of participants with at least one episode of Grade 2 or higher diarrhoea up to 24 weeks.
The registry reports enrollment of 62, a status of terminated, and a primary completion date of 2017-10-19. It lists 20 outcome measures and one analysis. The primary-outcome description includes withdrawal assumptions, but is truncated. A single primary comparison and the reason for termination are not reported in the registry record.
Safety counts are reported for serious and other adverse events, along with deaths and selected serious-event terms. These are descriptive figures; the record does not report statistical comparisons for them or establish treatment attribution.