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 For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib (NCT00526669), a non-randomized phase 2 study. The primary outcome is Change From Start of Run-in Period in Biomarker Expression Levels at Day 0.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00526669 |
| Phase | Phase 2 |
| Condition | Neoplasms, Gastrointestinal Tract |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 68 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Participants with untreated, first-line gastric cancer were the intended population. The registry record describes the analyzed population as participants who entered the study and received at least one dose of lapatinib; only participants with viable samples contributed to biomarker analyses. The condition field is broader, listing gastrointestinal tract neoplasms.
Intervention
The study administered lapatinib and capecitabine. The biomarker assessment included a lapatinib run-in period, with expression measured at the start of monotherapy and again after seven days of study treatment. The registry record does not give further dosing details in the information available for this analysis.
Comparator
There was no concurrent comparator group. The allocation was non-randomized and the model was single-group. Participants therefore were not assigned to lapatinib and capecitabine versus a control treatment within this trial. Changes in expression were assessed within participants across the specified time points.
Primary question
The primary registered endpoint describes changes in intratumoral expression of genes in the 5-fluorouracil pathway and lapatinib-targeted genes. The broader study objective was to examine whether changes in 5-FU-pathway marker expression were associated with response to lapatinib plus capecitabine, independent of tumor erbB2 status. The registry record does not report numerical primary endpoint results or an estimate of such an association.
3. Trial Design
This was a completed, exploratory phase II, single-group study with non-randomized allocation and no masking. The registry record lists an enrollment of 68. It identifies GlaxoSmithKline as sponsor and gives a start date of 2008-03 and primary completion date of 2011-04. These details describe the registered study, but do not establish how many participants contributed to every outcome or analysis.
All participants received the lapatinib and capecitabine intervention. The biomarker endpoint compared expression at the start of monotherapy, identified as Day -7, with expression after the lapatinib run-in, identified as baseline and assessed at Day 0. The stated timeframe is baseline and after 7 days of study treatment. The endpoint was reported using a median and full range, with results expressed as ratios of normalized target-gene expression to beta actin.
The single-group structure matters for interpretation. There was no randomized control arm to distinguish treatment-related changes from changes that might occur over time or from other influences. The within-participant biomarker comparison can describe change over the specified interval among participants with viable samples, but it is not a randomized comparison of treatments. The registry record does not report a protocol-level account of the sample-size justification, interim analyses, or detailed statistical analysis plan.
The record lists 26 outcome measures and 7 analyses. Secondary outcomes include progression-free survival, overall survival, time to progression under different competing-risk definitions, time to response, duration of response, best overall response categories, and changes in albumin toxicity grade. Their inclusion identifies outcomes of interest; it does not provide their numerical results. The intervention was recorded as a drug, and the study status is completed.
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: After an initial tumor biopsy (biop.), participants (par.) received lapatinib monotherapy in a 7-day Run-in Period, followed by a second biop. After the second biop., par. received a 14-day course of capecitabine in combination with lapatinib, which continued in the absence of treatment-related toxicity, until disease progression or withdrawal.
7-Day Run-in Monotherapy Treatment Phase
| Stage | Lapatinib | Lapatinib + Capecitabine |
|---|---|---|
| STARTED | 67 | 0 |
| COMPLETED | 67 | 0 |
| NOT COMPLETED | 0 | 0 |
Combined Treatment Phase
| Stage | Lapatinib | Lapatinib + Capecitabine |
|---|---|---|
| STARTED | 0 | 67 |
| COMPLETED | 0 | 59 |
| NOT COMPLETED | 0 | 8 |
Reasons for not completing this period:
| Reason | Lapatinib | Lapatinib + Capecitabine |
|---|---|---|
| Lost to Follow-up | 0 | 2 |
| Withdrawal by Subject | 0 | 2 |
| Sponsor Terminated Study | 0 | 2 |
| Death | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants who entered the study and received at least one dose of lapatinib. Only those participants contributing viable samples were analyzed. Different participants contributed samples for different biomarkers.
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 | Lapatinib + Capecitabine |
|---|---|---|
| Participants analysed | 67 | |
| Age, Continuous | Years | 61.4 (SD 12.57) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 50 |
| Race/Ethnicity, Customized: White - White/Caucasian/European Heritage | participants | 34 |
| Race/Ethnicity, Customized: Asian - East Asian Heritage | participants | 30 |
| Race/Ethnicity, Customized: American Indian or Alaskan Native | participants | 2 |
| Race/Ethnicity, Customized: Asian - South East Asian Heritage | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Start of Run-in Period in Biomarker Expression Levels at Day 0, measured over evaluated at baseline and after 7 days of study treatment.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ratio |
| Endpoint classification | not reduced to a single comparison |
The primary registered endpoint is change from the start of the run-in period in biomarker expression levels at Day 0. It concerns intratumoral expression of genes involved in the 5-fluorouracil pathway and genes targeted by lapatinib. Change was defined as the expression measured after the lapatinib run-in, at baseline, minus expression measured at the start of monotherapy, Day -7. Results were to be expressed as ratios of normalized target-gene expression to beta actin, with a median and full range.
Biomarker change is used to characterize a biological response to the treatment period and to explore whether those changes relate to clinical outcomes. The broader objective was to assess whether changes in 5-FU-pathway marker expression were associated with response to the combination independently of tumor erbB2 status. A biomarker change is not itself evidence that a marker predicts clinical response: that requires an analysis of the relationship between marker change and a clinical outcome, together with enough detail to evaluate the estimate and its uncertainty.
The registry record does not report the numerical expression changes, the number of viable samples for each marker, or numerical association estimates. The endpoint definition is available, but the observed primary results cannot be interpreted from the registry entries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a biological question rather than a randomized treatment comparison. It specifies changes in intratumoral gene expression across the lapatinib run-in and sets the broader objective of examining whether changes in 5-FU-pathway markers are associated with response to lapatinib and capecitabine. That distinction is important: a change in a biomarker and an association between a biomarker change and clinical response are related but separate results.
For the primary endpoint, the direction of change is defined as the post-run-in measurement minus the measurement at the start of monotherapy. The registry record does not include the observed medians, full ranges, or the number of participants contributing to individual biomarkers. It also does not report an estimate of the association between marker changes and response. Consequently, the magnitude, direction, and precision of the primary biomarker findings are not reported in the registry record.
The trial enrolled 68 participants, while its biomarker population required receipt of at least one lapatinib dose and a viable sample. Different participants contributed samples for different biomarkers. Thus the enrollment figure should not be treated as the sample size for every gene-expression result. Without marker-specific sample counts and results, readers cannot assess how much information supports each biomarker estimate or whether sample availability differed across markers.
The design was single-group and non-randomized, with no masking. Biomarker changes observed across the run-in are descriptive within-participant changes in this study. They do not, by themselves, establish that treatment caused a change, nor do they establish that a biomarker identifies who will respond. A randomized control group is not part of the registered design, so the trial does not provide a like-for-like control comparison.
The registry lists clinical outcomes including progression-free survival, overall survival, response measures, and time-to-progression measures with specified competing-risk definitions. It also lists 26 outcome measures and 7 analyses. The numerical findings for those outcomes are not reported in the registry record. The presence of outcomes in a registry is not a substitute for effect estimates, uncertainty intervals, event counts, or descriptions of the analyses actually performed.
Accordingly, the record supports an account of the study question, endpoint definition, and design, but not a quantitative conclusion about biomarker change or clinical efficacy. Any planning illustrations based on an observed effect are hypothetical design calculations, not observed power and not evidence that the treatment has a particular effect. The record's own analysis would take precedence if a recalculated estimate differed from a sponsor analysis; no discrepancy information is reported.
9. Statistical Methods Explained
What does the biomarker endpoint summarize?
The endpoint is a within-participant change in gene-expression ratios over the lapatinib run-in. The registry defines the change as the level after the run-in, at baseline, minus the level at the start of monotherapy, Day -7. Expression is normalized by relating the target gene to beta actin. The listed summary is the median with the full range. This is a descriptive summary of the distribution of observed changes, not a treatment-versus-control effect estimate.
In general, a median identifies the middle of an ordered set of observations and is less influenced by extreme values than a mean. The full range describes the lowest and highest observed values, but it does not show how observations are distributed between those endpoints. Neither summary alone quantifies the precision of an estimated population effect in the way a confidence interval would. The registry record does not report confidence intervals for this primary endpoint.
Why does the time-point definition matter?
The endpoint compares measurements at two specified stages: the start of monotherapy and after the lapatinib run-in. A change score depends on both measurements and on the direction in which subtraction is defined. Here, the later measurement is subtracted from the earlier measurement in the order stated by the registry: after-run-in baseline minus start-of-monotherapy Day -7. Interpretation of a positive or negative value would therefore depend on this definition and on the biological scale of the ratio. Numerical values are not reported in the registry record, so the observed direction cannot be described.
In general, repeated measurements can help describe change within the same participant because each participant contributes measurements at different times. However, such a comparison does not automatically separate treatment effects from time-related changes, measurement variability, or other concurrent influences. This study had no randomized control group to provide a concurrent comparison for the biomarker endpoint.
What does a biomarker association require?
The study objective concerns whether changes in marker expression are associated with response. An association analysis asks whether participants with different biomarker changes also tend to have different clinical outcomes. That is distinct from reporting the distribution of biomarker changes alone. A useful report would identify the clinical response definition, the analysis method, the estimated association, its uncertainty, and the number of participants contributing to it. Those numerical results and details are not reported in the registry record.
In general, association does not by itself demonstrate that a marker causes response or that the marker can reliably predict outcomes for other participants. Such interpretation depends on design, measurement quality, the analysis approach, and replication. The study's exploratory phase II designation is consistent with a question about biological and clinical relationships, but the registry entry does not give the full analysis plan or a sample-size justification.
How should uncertainty and over-dispersion be understood?
In general, a confidence interval describes a range of values compatible with an estimate under the assumptions of the statistical model. Wider intervals indicate less precision; narrower intervals indicate greater precision, while still depending on the model and the data. A p-value, when reported, describes how unusual the observed data would be under a specified null model. It is not the probability that the null hypothesis is true or a measure of clinical importance. No primary endpoint confidence interval or p-value is reported in the registry record.
In general, over-dispersion occurs when variability is greater than a statistical model assumes. If ignored, standard errors and uncertainty assessments can be too optimistic. It can matter for analyses of counts or other outcomes whose variance is model-dependent. The registry record does not identify the model used for the biomarker endpoint or the clinical outcome analyses, so it is not possible to assess whether over-dispersion was relevant or how it was handled.
What do planning calculations represent?
In general, sample-size calculations depend on assumptions about the target effect, variability, significance level, power, and allocation. Planning illustrations based on an observed effect are hypothetical calculations: they do not describe the number of participants actually analyzed, and they are not observed power. The stated planning assumptions for any illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; time-to-event calculations use total events, while other calculations use participants per arm. Those assumptions describe a hypothetical two-arm planning framework, not this trial's single-group design.
The registry record does not report the trial's own sample-size justification or sufficient primary endpoint results to assess precision. The planning assumptions should therefore be read as illustrations rather than as a record of how the study was designed.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 26 outcome measures and 7 analyses. Multiple outcomes and analyses create the possibility of multiplicity: when many hypotheses are examined, the chance of at least one apparently unusual finding can increase. In general, prespecified priorities and multiplicity adjustments can help readers distinguish confirmatory tests from exploratory analyses. The registry record does not report whether multiplicity was addressed, which outcomes were treated as primary for each analysis, or whether any adjustment was used.
The primary endpoint description identifies an ITT population as all participants who entered the study and received at least one dose of lapatinib. It also states that only participants contributing viable samples were analyzed, and that different participants contributed samples for different biomarkers. This means biomarker-specific analysis populations may differ. The record does not report marker-specific sample counts, the extent or reasons for unavailable samples, or methods for handling missing measurements.
In general, missing data can affect estimates if participants with unavailable measurements differ systematically from those with observed measurements. The consequences depend on why data are missing, the amount of missingness, and the analysis method. The registry description does not say whether missingness was assessed or whether any imputation or sensitivity analyses were conducted.
Although enrollment was 68, this number should not be assumed to apply to every endpoint. The safety figures list 67 participants at risk. The statistical analysis plan, details of analysis populations for secondary outcomes, and handling of missing clinical outcome data are not reported in the registry record. These omissions limit assessment of how broadly each reported estimate would apply, even if numerical estimates were available.
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 |
|---|---|---|---|
| Lapatinib + Capecitabine | 22 | 67 | 32.8% |
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 |
|---|---|
| Lapatinib + Capecitabine | 63 of 67 |
Most frequent serious adverse event terms
| Event term | Organ system | Lapatinib + Capecitabine |
|---|---|---|
| Vomiting | Gastrointestinal disorders | 4 of 67 |
| Diarrhea | Gastrointestinal disorders | 3 of 67 |
| Decreased appetite | Metabolism and nutrition disorders | 3 of 67 |
| Nausea | Gastrointestinal disorders | 2 of 67 |
| Anemia | Blood and lymphatic system disorders | 2 of 67 |
| Abdominal distension | Gastrointestinal disorders | 1 of 67 |
| Abdominal pain | Gastrointestinal disorders | 1 of 67 |
| Dyspepsia | Gastrointestinal disorders | 1 of 67 |
| Gastrointestinal hemorrhage | Gastrointestinal disorders | 1 of 67 |
| Gastroesophageal reflux disease | Gastrointestinal disorders | 1 of 67 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lapatinib + Capecitabine |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 27 of 67 |
| Decreased appetite | Metabolism and nutrition disorders | 23 of 67 |
| Fatigue | General disorders | 23 of 67 |
| Nausea | Gastrointestinal disorders | 23 of 67 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 17 of 67 |
| Anemia | Blood and lymphatic system disorders | 16 of 67 |
| Abdominal pain | Gastrointestinal disorders | 13 of 67 |
| Abdominal pain upper | Gastrointestinal disorders | 12 of 67 |
| Vomiting | Gastrointestinal disorders | 12 of 67 |
| Asthenia | General disorders | 11 of 67 |
Serious events with the highest arm-level rate: vomiting (6.0%), diarrhea (4.5%), decreased appetite (4.5%), nausea (3.0%), anemia (3.0%).
The safety entry lists 67 participants at risk in the lapatinib-plus-capecitabine group. It records 22 participants as having at least one serious adverse event and 63 as having an adverse event in the other-event category. These counts describe participants with events in the recorded categories; they do not state how many total episodes occurred or how severe every event was.
The most frequently listed serious adverse event terms are vomiting (6.0%), diarrhea (4.5%), decreased appetite (4.5%), nausea (3.0%), anemia (3.0%), and abdominal distension (1.5%). The registry record does not give event counts alongside those percentages in the information, nor does it report details such as timing, duration, or attribution for each term. The death count is not reported in the registry record.
These figures describe safety observations in a single-group study. With no control group, the record does not support a like-for-like comparison of adverse event rates against another treatment. Event listings also do not by themselves establish that the intervention caused an event. Safety interpretation should remain descriptive and be kept separate from conclusions about biomarker change or clinical outcomes.
12. What the Result Does, and Does Not, Mean
The study addresses a biologically specific question: whether changes in expression of genes involved in the 5-FU pathway are associated with response to lapatinib and capecitabine in first-line gastric cancer, independent of tumor erbB2 status. Its registered primary endpoint measures change in intratumoral gene expression over the lapatinib run-in. This design and endpoint provide a framework for investigating biomarker behavior during treatment.
The registry record does not report numerical results for the primary biomarker endpoint or an estimate of the relationship between biomarker change and response. It also does not report numerical results for the listed secondary clinical outcomes in the information available for this analysis. Therefore, the record does not establish the size or direction of biomarker changes, the precision of an association, or the clinical outcome pattern.
The design cannot support a randomized comparison of lapatinib plus capecitabine with a control treatment, because it was a single-group, non-randomized study. Within-participant biomarker changes can describe what was observed at the specified time points among participants with viable samples, but do not alone show that treatment caused those changes. Likewise, a biomarker association, even if reported, would not by itself prove that the biomarker causes response or reliably predicts outcomes outside the study.
The results should also be considered in light of the differing biomarker sample populations, the absence of marker-specific sample counts in the record, and the lack of reported methods for missing data and multiplicity. The enrollment of 68 does not identify the number contributing to each biomarker or clinical analysis. The appropriate conclusion is therefore limited to the registered purpose, design, endpoint definition, and recorded safety figures; quantitative efficacy and biomarker conclusions are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for linking a short-term biological measurement to a broader clinical question. It measured intratumoral expression of genes in the 5-fluorouracil pathway and lapatinib-targeted genes around a lapatinib run-in, while its stated objective concerned whether changes in 5-FU-pathway markers were associated with response to combination treatment. That relationship requires more than a description of the biomarker distribution: it requires an analysis that connects marker change to a defined clinical outcome.
The study also illustrates why analysis populations matter in biomarker research. Only participants with viable samples were analyzed, and different participants contributed samples for different biomarkers. An overall enrollment count cannot be assumed to describe every marker-specific analysis. Without marker-level sample counts and missing-data details, readers cannot evaluate the information base for each estimate or judge whether available samples might differ from unavailable ones.
Its single-group, non-randomized structure is another central statistical feature. It allows observation of outcomes and within-participant changes during the study, but offers no randomized control comparison. This limits causal interpretation and makes clear separation of descriptive findings from treatment effects especially important.
Finally, the registry lists many outcome measures and analyses, while the multiplicity approach and detailed analysis plan are not reported. The trial therefore highlights the value of complete reporting: endpoint definitions, analysis populations, sample counts, uncertainty estimates, missing-data methods, and multiplicity handling are all needed to assess how strongly a biomarker result supports a clinical interpretation. The registry record documents the research question and design, but not the numerical primary results needed to judge the proposed association.
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 primary endpoint is a biomarker change measured around the lapatinib run-in, while the broader objective concerns association with response to the combination. The registry record does not provide numerical results for either the biomarker change or that association. This prevents assessment of effect direction, magnitude, precision, and consistency across markers.
The study was single-group and non-randomized, with no masking. Consequently, there is no concurrent randomized control group for comparing biomarker changes, clinical outcomes, or adverse events. Observed changes across time points cannot by themselves isolate an effect of treatment from other influences. The registry record does not report additional design or analysis details that would address this limitation.
Biomarker analyses included only participants with viable samples, and participants differed across biomarkers. The record does not give the number of viable samples for each marker, reasons samples were unavailable, or methods for handling missing measurements. Enrollment of 68 therefore cannot be treated as the sample size for every biomarker analysis.
The registry lists 26 outcome measures and 7 analyses but does not report whether multiplicity was controlled or which analyses were considered confirmatory. It also does not report the detailed statistical analysis plan, the trial's sample-size justification, or interim analyses. The numerical results for secondary outcomes are not reported in the registry record, limiting interpretation beyond the endpoint definitions and recorded safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study For Patients With Untreated Gastric Cancer Who Will Receive Capecitabine And Lapatinib — NCT00526669.
- Registry record last updated 2016-01-29; status last verified 2015-07.
- Results first posted 2012-10-01.
- 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
NCT00526669 was a completed exploratory phase II study of lapatinib and capecitabine in first-line gastric cancer. It was single-group, non-randomized, and unmasked, with an enrollment of 68. The registered primary endpoint measured change in intratumoral expression of genes involved in the 5-fluorouracil pathway and lapatinib-targeted genes between the start of monotherapy and after the lapatinib run-in.
The broader objective was to examine whether changes in 5-FU-pathway markers were associated with response, independent of tumor erbB2 status. Biomarker analyses were limited to participants with viable samples, with different participants contributing to different markers. The registry lists 26 outcome measures and 7 analyses. Numerical primary biomarker results and the association with response are not reported in the registry record.
The safety record lists 67 participants at risk, 22 with serious adverse events, and 63 with other adverse events. The design provides no randomized control comparison.