Concentration and Activity of Lapatinib in Vestibular Schwannomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Concentration and Activity of Lapatinib in Vestibular Schwannomas (NCT00863122), a non-randomized early/phase 1 study. The primary outcome is Median Steady-state Lapatinib Plasma Concentrations at the Time of Surgical Resection.

2. Clinical Question

Vestibular schwannomas are tumors affecting the auditory nerves and can cause hearing loss. The registry describes surgery and radiation as usual approaches to preserving hearing, while noting that these procedures carry risks and may not prevent hearing loss for everyone. It presents lapatinib, a drug used for breast cancer, as a candidate for investigation in vestibular schwannoma.

The study’s primary question is pharmacological: after lapatinib exposure before surgery, what is the median steady-state concentration of the drug in plasma at the time of surgical resection? This endpoint addresses whether drug is present in the circulation at the surgical time point. The study also lists secondary questions about ErbB2 phosphorylation, markers of tumor proliferation and cell death, and differences in lapatinib concentration between NF2-related and idiopathic vestibular schwannomas. It further describes NF2 gene mutation analysis and protein expression work.

The registry’s broader rationale is that measuring drug reaching a tumor may inform future investigation of drug treatment for vestibular schwannoma. However, plasma concentration is not itself a measurement of hearing preservation, tumor shrinkage, or prevention of tumor growth. Those clinical effects are not the primary endpoint described in the record, and numerical results for the listed outcomes are not reported in the registry record.

The listed arms are not a randomized, like-for-like comparison. The control subjects receive no intervention before surgery, while the lapatinib group receives the drug before surgery. As a result, the main question should be read as an exploratory concentration assessment, not as a controlled estimate of a treatment effect on clinical outcomes.

3. Trial Design

The registry classifies NCT00863122 as an early-phase study with non-randomized allocation, no masking, and a parallel model. It lists enrollment of 26 and a completed status. The listed study dates are 2009-06 for start and 2014-08 for primary completion. The sponsor is Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

The lapatinib arm description states that participants receive lapatinib for 10 days before vestibular schwannoma resection. The control description states that control subjects receive no intervention before resection. The primary endpoint timeframe is at surgery, 10-13 days from starting drug. The registry record does not report how participants were assigned to these arms or provide enough information to reconstruct the recruitment and allocation process.

Because allocation is non-randomized and the arms differ in whether they receive lapatinib, comparisons between them cannot be interpreted as if treatment assignment were randomized. The registry itself flags the arms as not being a like-for-like control comparison. Any differences between groups could reflect differences in who entered each arm, in addition to or instead of an effect of the intervention.

The primary outcome concerns steady-state plasma lapatinib concentration at surgery. The registry record also lists secondary laboratory and tumor-related outcomes. It does not report the numerical primary outcome result or numerical results for the secondary outcomes. The outcome-population note says that samples were lost following a freezer failure during a natural disaster, but the note is truncated and does not fully describe the analysis population. The registry record does not report a statistical analysis plan, sample-size justification, or details of any interim analyses.

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: Patients could enroll on control (no drug) or lapatinib arms. 20 people were consented for the the lapatinib arm, but one patient withdrew consent prior to completion of eligibility screening and enrollment. So 19 patients enrolled on the lapatinib arm.

Overall Study

Analysis population for the primary outcome, as defined in the registry: In the lapatinib group, 10 tissue and plasma samples were lost from analysis due to a freezer failure during a natural disaster denaturing the samples. 1 blood sample was contaminated, but tissue was available. Control group did not get any drug. A total of 8 participants of 19 given drug had data for analysis.

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.

6. Primary Endpoint

The registry lists the primary outcome as Median Steady-state Lapatinib Plasma Concentrations at the Time of Surgical Resection, measured over At time of surgery, 10-13 days from starting drug..

The primary endpoint is the median steady-state lapatinib concentration in plasma, measured in ng/mL at the time of surgical resection. The stated timeframe is 10-13 days after starting the drug. A median describes the midpoint of the observed concentration distribution: it is a summary of the measurements, not a measure of the drug’s effect on tumor growth, hearing, or another clinical outcome.

Concentration is used to address whether lapatinib is present in plasma at the surgical time point after the planned preoperative exposure. That is relevant to the study’s exploratory pharmacological aim. The registry also specifies full range as the measure of dispersion. A range describes the lowest and highest observed values and indicates the spread covered by the measurements, although it does not show how observations are distributed between those endpoints.

The registry record does not report the median concentration or its full range. It also does not provide a confidence interval or another uncertainty estimate for this endpoint. Consequently, the numerical concentration and its precision cannot be described from the available registry information. Even with a reported plasma concentration, plasma measurement alone would not establish the concentration in tumor tissue or demonstrate a clinical benefit; those are distinct questions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how observations are summarized, compared, and interpreted. The registry record identifies the primary summary as a median with full range, but it does not report a detailed statistical analysis plan. The explanations below are general descriptions of the named methods and design features, not claims about additional procedures used in this study.

What does a median summarize?

In general, a median is the central value after observations are ordered. It is less influenced by unusually high or low measurements than an arithmetic mean. This can make it a useful descriptive summary when concentrations are skewed or include extreme observations. A median alone does not reveal the shape of the distribution, and the full range provides only its endpoints. Individual observations or additional distribution summaries would be needed to understand the pattern more fully.

For this endpoint, the record specifies a median concentration and full range in ng/mL at surgery. It does not give the observed median, the range, or the number of evaluable concentration measurements. No inference about the distribution or its precision can be made without those results. The registry record does not report a confidence interval for the median.

What does steady state mean in this context?

In general, steady state refers to a condition in which drug input and elimination have produced a relatively stable concentration pattern over time. It is a pharmacological concept, not a statistical result. The registry labels the endpoint as a steady-state plasma concentration and places measurement at surgery, 10-13 days from starting drug. The record does not provide further details about how steady state was assessed or confirmed.

How should a concentration endpoint be distinguished from a clinical outcome?

In general, a drug concentration measures exposure in a sampled biological compartment. It is not interchangeable with evidence of target engagement, a change in tumor behavior, or a patient-centered outcome. The registry separately lists tumor-related secondary outcomes, including ErbB2 phosphorylation and markers of proliferation and cell death. It also lists a comparison of concentration in NF2-related versus idiopathic vestibular schwannomas. Those are distinct questions requiring their own measurements and analyses. Numerical results for these outcomes are not reported in the registry record.

Why do missing measurements matter?

In general, missing measurements reduce the information available and can affect interpretation if the availability of data is related to participant characteristics or measured values. A technical loss of samples can still leave uncertainty about whether the remaining observations represent the intended study population. The registry attributes losses of tissue and plasma samples to a freezer failure during a natural disaster and notes a contaminated blood sample with tissue available. It does not report a complete account of the affected samples for each outcome, a missing-data analysis, or the assumptions used to handle missing measurements.

What does non-randomized allocation imply?

In general, random allocation helps balance both measured and unmeasured participant characteristics between treatment groups, on average. Non-randomized allocation does not provide that design-based protection. A comparison between groups may be confounded by how participants entered each group or by other differences. Here, the registry describes lapatinib and control arms, but explicitly notes that they are not a like-for-like control comparison. The record does not report adjustment methods that would address group differences.

What can be learned from the registry’s stated analysis details?

The registry gives the endpoint summary type and dispersion measure, and it describes the outcome timeframe. It does not report inferential methods, a statistical analysis plan, a sample-size justification, or interim-analysis procedures. A confidence interval would generally communicate the uncertainty around an estimated quantity, while a hypothesis test would assess compatibility with a specified null hypothesis under its assumptions. Neither an interval nor a test result for the primary endpoint is reported in the registry record. No p-value or sponsor analysis result is available in the record.

The record includes general planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect defined as a stated fraction of an observed effect. Those are described as planning illustrations rather than the trial’s own design. Such illustrations do not establish how many participants were actually analyzed, and they are not observed power. The registry record does not report the numerical illustration results in the material available for this analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary plasma concentration endpoint and several secondary aims: ErbB2 phosphorylation, tumor proliferation and cell-death markers after lapatinib exposure, concentration differences between NF2-related and idiopathic vestibular schwannomas, and NF2 gene mutation and protein-expression work. Multiple outcomes and subgroup questions can create multiplicity: the more hypotheses examined, the greater the chance that some findings appear noteworthy by chance if results are interpreted without accounting for the number of analyses.

The registry record does not report a multiplicity adjustment, a hierarchy for testing secondary outcomes, or a statistical analysis plan specifying which findings would be confirmatory versus exploratory. It also does not report numerical results for the secondary outcomes. The listed aims should therefore be understood as questions the study planned to explore, not as evidence that each question was answered.

Missingness is a particular concern because the record reports that 10 tissue and plasma samples were lost from analysis after a freezer failure during a natural disaster. It also reports 1 contaminated blood sample, with tissue available. The population note is truncated after stating that 8 participants of 19 given drug had data. The registry record does not fully describe outcome-specific availability, the handling of each missing measurement, or whether analyses used all available observations or another approach.

The registry lists 26 enrolled participants, but does not give a complete analysis population for the primary endpoint. The number enrolled, the number receiving drug, and the number with endpoint data are different concepts and should not be treated as interchangeable. The record does not report reasons for any other missing data, nor does it provide a missing-data sensitivity analysis. These reporting gaps limit assessment of how representative the analyzed measurements are of the enrolled participants.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s serious adverse event fields list 19 participants at risk in the lapatinib group and 0 serious events affecting participants in that group. The control group fields list 0 participants at risk and 0 serious events. With no control participants recorded as at risk in these fields, the control entries cannot provide a meaningful safety comparison.

For other, non-serious adverse events, the registry lists 19 participants at risk and 12 affected in the lapatinib group. It lists 0 at risk and 0 affected in the control group. These are the registry’s group-level counts; the record does not provide event-level descriptions in the posted adverse-event information, and the list of top serious-event terms is empty. The term “other events” should not be read as a count of distinct event types unless the record explicitly defines it that way.

These fields describe recorded adverse events, not a complete estimate of risk. They do not establish whether an event was caused by lapatinib, and the lack of a usable control group prevents a comparative interpretation. The registry summary characterizes lapatinib as safe with few side effects, but the listed event counts alone do not support a conclusion about comparative safety. Additional definitions, event details, and complete follow-up information are not reported in the registry record.

12. What the Result Does, and Does Not, Mean

The study is designed to explore lapatinib exposure around vestibular schwannoma surgery. Its primary endpoint is the median steady-state plasma concentration at resection, and its secondary aims include tumor markers and comparisons involving NF2-related and idiopathic tumors. This makes the record relevant to understanding the questions researchers sought to examine.

The record does not report the numerical primary endpoint result. It therefore cannot establish what plasma concentration was observed or how much it varied across measured participants. It also does not report numerical results for the secondary outcomes. The available registry information cannot show whether drug reached the tumor tissue at a particular concentration, whether tumor biology changed, or whether hearing or tumor growth outcomes improved.

Even a measured plasma concentration would answer a pharmacological question rather than, by itself, a clinical-effectiveness question. Evidence about drug exposure, tissue concentration, biological activity, tumor behavior, and hearing outcomes represents different levels of evidence. The registry’s study rationale discusses the possibility of future treatment exploration, but that rationale is not a finding of benefit.

The design also limits interpretation of between-arm comparisons. Allocation was non-randomized, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The control arm is described as receiving no preoperative intervention, but the adverse-event fields record 0 participants at risk in that group. Accordingly, those fields cannot be used to establish a comparative safety profile.

The study should be read as an exploratory preoperative investigation with incomplete outcome reporting in the registry record. The participant and sample counts indicate that data availability is an important consideration, but the record does not fully reconcile enrollment, treatment exposure, and endpoint analysis. Without numerical outcome estimates, uncertainty measures, and a complete analysis population, the magnitude and precision of any observed result cannot be assessed.

13. Why This Trial Matters Statistically

This trial is statistically notable because it separates a pharmacological measurement from a clinical treatment question. The primary endpoint concerns plasma concentration at surgery, while the registry’s motivation refers to possible future effects on vestibular schwannoma. A concentration measurement may help characterize exposure, but it cannot substitute for direct evidence about tumor response or hearing outcomes.

The study also illustrates the interpretive limits of a non-randomized comparison. The registry describes parallel lapatinib and control arms but states that they are not a like-for-like comparison. That warning matters because differences between groups may reflect selection or other group differences rather than treatment. The record does not report methods that would resolve this issue.

Sample loss is another important statistical feature. The registry attributes the loss of 10 tissue and plasma samples to freezer failure during a natural disaster and notes 1 contaminated blood sample. Such loss can reduce the information available for estimating concentration and examining tumor-related outcomes. Because the outcome-population description is truncated, the extent and consequences of missing measurements cannot be fully evaluated.

Finally, the registry’s stated median and full range would describe the distribution of concentrations, but the numerical values are not reported. Without an estimate, range, and uncertainty measure, readers cannot assess the level or precision of exposure. The record’s secondary questions and adverse-event counts provide context, but they do not fill that gap. The statistical importance of this study lies in its exploratory measurement aims and in the need to distinguish those aims from claims about clinical benefit or comparative safety.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation in interpreting the registry record is that the numerical primary endpoint result is not reported. Although the endpoint is defined as median steady-state plasma concentration at surgery with full range, neither the median nor the range appears in the record information available for this analysis. No confidence interval or other uncertainty measure is reported.

The analysis population is also unclear. The record lists enrollment of 26 and says that 19 participants were given drug. It reports loss of 10 tissue and plasma samples after a freezer failure during a natural disaster, and 1 contaminated blood sample for which tissue was available. The population note ends after stating that 8 participants of 19 given drug had data, without completing the description. It is not possible to determine from the registry record which outcome measurements were available for each participant or how the sample losses affected each analysis.

Non-randomized allocation and the registry’s explicit warning that the arms are not a like-for-like control comparison limit causal interpretation. The record does not report allocation details or statistical adjustment for potential group differences. The control group’s adverse-event fields list no participants at risk, preventing a meaningful adverse-event comparison.

The record lists multiple secondary outcomes but does not report their numerical results, an analysis plan, or how multiplicity was handled. It also does not report a sample-size justification or interim-analysis details. These omissions constrain assessment of precision, selective analysis, and the scope of conclusions that can be drawn. The endpoint is a plasma concentration, not a direct measure of hearing preservation, tumor shrinkage, or tumor growth.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Concentration and Activity of Lapatinib in Vestibular Schwannomas — NCT00863122.
• Registry record last updated 2021-01-12; status last verified 2020-12.
• Results first posted 2018-11-26.
• 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.

18. Record Summary

NCT00863122 is listed as a completed early-phase, non-randomized, unmasked, parallel study sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The registry lists enrollment of 26, a start date of 2009-06, and primary completion in 2014-08.

The lapatinib arm received the drug for 10 days before vestibular schwannoma resection; control subjects received no intervention before surgery. The primary endpoint was median steady-state lapatinib plasma concentration at surgery, 10-13 days after starting drug, with full range specified as dispersion. Numerical primary and secondary outcome results are not reported in the registry record.

The record describes loss of tissue and plasma samples due to a freezer failure during a natural disaster, a contaminated blood sample, and an incomplete outcome-population note. It also cautions that the non-randomized arms are not a like-for-like control comparison. These features limit assessment of the endpoint results and any between-arm interpretation.