Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation (NCT00858403), a na phase 2 study. The primary outcome is Number of Participant Progressors vs. Non-progressors With Tumor Response.

2. Clinical Question

The question links a laboratory measure of drug-related target modulation with clinical disease categorization. ERK phosphorylation was assessed in cancer cells exposed to dasatinib outside the body, while progressor status was determined using standard Response Evaluation Criteria in Solid Tumors (RECIST). The planned analysis was therefore not simply a count of tumor responses: it sought to compare the degree of inhibition between two categories defined by disease progression status.

The registry describes the study as an investigation of how people with advanced NSCLC respond to dasatinib, and lists several secondary aims involving response, progression-free survival, serious adverse events, inhibition, drug concentration, and mutation. However, the planned primary analysis could not be completed because accrual was 7 participants and the target was 40. The registry record does not report a completed primary comparison or a result for the extent of inhibition by progression category. Consequently, the clinical question remains a description of the study's objective, not a conclusion about whether the groups differed.

3. Trial Design

This was a Phase II, single-group study of dasatinib in advanced non-small cell lung cancer. The registry records allocation as not applicable and masking as none. There was no randomized allocation and no comparator arm, so the design does not support a like-for-like treatment comparison. All enrolled participants were listed under treatment with dasatinib.

The planned regimen was dasatinib 140 mg orally every day, with continuous dosing starting on Day #1. The record says that this dose was selected based on experience in patients with solid tumors who had prior chemotherapy. The registry does not give further details about eligibility criteria, treatment duration rules, dose modification rules, adherence, or concomitant treatment; those details are not reported in the registry record.

The study started in 2009-03, with primary completion recorded as 2010-07. Its status is terminated. Enrollment was 7, while the primary outcome description states that the target accrual was 40 and that low accrual prevented completion of the planned analysis. The registry record does not explain why the study was terminated or provide further details about recruitment.

The primary objective concerned whether the extent of ex vivo ERK phosphorylation inhibition differed between participants categorized as progressors and non-progressors by RECIST. Listed secondary outcomes include response to dasatinib, progression-free survival at 6 months, serious adverse events, inhibition response by progression status, and correlations involving inhibition, drug concentration, mutation, disease control, and response. Although these objectives are listed, the record does not report completed analyses for them. The study design and enrollment therefore establish what investigators intended to examine, but not whether those questions were answered.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The low accrual of 7 participants prevented us from completing the planned analysis. Target accrual was 40.

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 Number of Participant Progressors vs. Non-progressors With Tumor Response, measured over 1 year, 4 months.

The primary endpoint was described as the number of participants who were progressors versus non-progressors with tumor response. Its accompanying description clarifies the intended analysis: assess whether the extent of inhibition of ERK phosphorylation in lung cancer cells exposed ex vivo to dasatinib differed between patients categorized as progressors or non-progressors using RECIST. The planned timeframe was 1 year, 4 months.

This endpoint connects a biological measure to a clinical classification. ERK phosphorylation is a marker of signaling activity, and its inhibition after ex vivo exposure to a drug can be studied as evidence of target modulation in the tested cells. Comparing inhibition across progression categories could help characterize whether the laboratory response tracked with clinical disease status. This is a general rationale for a translational endpoint; it does not establish that inhibition predicts an individual patient's outcome or that the measure is clinically useful.

The registry says low accrual prevented completion of the planned analysis. It reports no endpoint unit, parameter, or dispersion, and no completed result for the comparison. The precise endpoint summary and the statistical test planned for the comparison are not reported in the registry record. Thus, the endpoint's intended purpose can be described, but its estimated group difference, uncertainty, and evidential strength cannot be evaluated from the registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described by the registry are limited. It identifies a Phase II study with a single-group model, allocation recorded as not applicable, and no masking. It states the planned regimen and the primary biological-clinical question, but does not specify the statistical test, estimator, model, adjustment strategy, or analysis population for that question. These details are not reported in the registry record. The explanations below describe general statistical concepts relevant to the stated objective, rather than methods confirmed as having been used.

What does a single-group design allow?

In a single-group study, treatment outcomes are observed in participants who receive the study intervention, without a separate control group in the design. Such observations can describe what occurred among enrolled participants and can inform the feasibility of measuring outcomes. They cannot, by themselves, distinguish the effect of treatment from the natural course of disease, selection of participants, concurrent care, or other influences. A randomized control group is generally used to make a more direct comparison by balancing factors that could otherwise differ between groups.

That distinction applies to both clinical and laboratory outcomes. A laboratory measure can change after ex vivo exposure, but without a relevant comparison the record cannot establish how that change relates causally to treatment in the body or how it compares with an alternative treatment. The planned comparison between progressors and non-progressors is an internal comparison by outcome category, not a randomized treatment comparison. The categories are defined by progression status, so any association between inhibition and status would not by itself prove that inhibition caused a clinical outcome.

What is the role of the endpoint categories?

The primary description distinguishes progressors from non-progressors using RECIST and proposes comparing the extent of ERK phosphorylation inhibition between those categories. This makes the endpoint a relationship between a laboratory measurement and a clinical classification. To estimate such a relationship, an analysis would ordinarily need a defined measurement scale, a rule for classifying progression, and a specified method for comparing the groups. The registry provides the biological measure and the classification framework, but does not report the measurement scale, operational details, or statistical method.

A comparison of continuous measurements between categories might be summarized using a difference in location or another suitable measure, depending on the distribution and design. If measurements are skewed or include outliers, methods that depend strongly on distributional assumptions may not describe the data well. These are general methodological considerations, not claims about the actual distribution in this study. The registry does not give individual measurements, group summaries, or diagnostics, so no particular method can be evaluated.

What does uncertainty mean?

A confidence interval is a general way to express the precision of an estimated effect. It shows a range of values compatible with the data under the assumptions of the method. A narrow interval generally indicates greater precision, while a wide interval indicates less precision. The interval does not remove bias from study design, measurement, or missing data, and it does not establish that an association is causal. No confidence interval or other uncertainty estimate for the primary comparison is reported in the registry record.

A p-value, when used, addresses how compatible the observed data are with a specified statistical null model; it is not the probability that the null hypothesis is true and does not measure clinical importance. The registry does not report a p-value for the primary comparison, or whether a formal test was conducted. It would therefore be inappropriate to infer statistical significance or its absence from the enrollment figure alone.

Why does low accrual matter?

The primary outcome description says that low accrual prevented completion of the planned analysis. The record gives enrollment as 7 and target accrual as 40. Limited accrual can leave a planned comparison with less information and less precision than intended. If the number of observations in each progression category is also limited, the estimated difference may be particularly uncertain. The record does not report the category counts, so the distribution between progressors and non-progressors cannot be described.

Accrual is not the only determinant of precision. The variability of the inhibition measure, the balance between categories, data completeness, and the analysis method also matter. Those details are not reported. The registry gives no basis for calculating a reliable precision estimate or for deciding whether the observed sample was sufficient to detect a scientifically meaningful difference. A planned target does not, on its own, explain the rationale for that target; the sample-size justification is not reported in the registry record.

Can the listed secondary outcomes be treated as confirmed findings?

No. The record lists secondary objectives, including response, progression-free survival at 6 months, serious adverse events, and associations involving inhibition, drug concentration, mutation, disease control, and response. Listing an outcome indicates that it was an intended subject of assessment, not that it was measured successfully or analyzed. The registry record does not report completed results for these outcomes. It also does not give definitions, analysis methods, effect estimates, or uncertainty intervals for most of them.

Overall, the methods information supports a description of the planned study and a general discussion of the statistical issues. It does not support reconstruction of an analysis or a judgment about the size, direction, or precision of the primary relationship.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes. When a study tests or estimates multiple outcomes, the chance of at least one apparently notable result can increase if the analyses are interpreted without accounting for multiplicity. A prespecified hierarchy or adjustment strategy can help clarify which findings are confirmatory and how multiple tests are handled. This is a general statistical consideration. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any interim analyses were planned or conducted.

The listed secondary outcomes span clinical events, safety, and laboratory relationships. Their definitions and analysis plans are not sufficiently detailed in the record to determine whether they were intended as confirmatory or exploratory. The registry reports 0 analyses. That entry does not substitute for a full statistical analysis plan, and it does not establish whether analyses were performed outside the registry record.

Missing-data handling and analysis populations are also not reported in the registry record. The entry does not describe how participants with incomplete laboratory measurements, unavailable progression assessments, treatment discontinuation, or incomplete follow-up would be handled. It does not identify an intention-to-treat, per-protocol, or other analysis population. These omissions matter because exclusions and missing observations can affect both the estimate and its precision, particularly when accrual is low.

The primary outcome description states that the planned analysis could not be completed because enrollment was 7 against a target of 40. It does not state whether partial measurements were available or whether any exploratory analysis was attempted. Without those details, the primary endpoint should be treated as an incomplete planned analysis rather than as a completed comparison with an unreported direction.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute renal failure (14.3%), cardiac ischemia/infarction (14.3%), death due to disease progression (14.3%), dyspnea (14.3%), fatigue (14.3%).

For the dasatinib group, the registry records 3 participants with serious adverse events among 7 at risk, and 6 participants with other adverse events among 7 at risk. These are counts recorded for the study group, not comparisons against a control group. The record lists acute renal failure, cardiac ischemia/infarction, death due to disease progression, dyspnea, fatigue, and fever in the absence of neutropenia as serious-event terms, each with a reported percentage of 14.3%.

These figures describe what was recorded in a small, uncontrolled study. They do not establish that dasatinib caused an event, and they cannot show whether the event frequency was higher or lower than it would have been under another treatment. The registry does not report a comparative safety analysis, event timing, severity grading details, or attribution to treatment. The deaths field is not populated; a death count is not reported in the registry record. The listed term “Death Due to Disease Progression” should therefore be read as a reported serious-event term, not as a complete account of mortality or a treatment-attribution statement.

Because the record reports participants with events, not a full event-level narrative, repeated events in an individual and the timing of events cannot be inferred. The counts are descriptive safety information and should be interpreted alongside the design and the limitations of the registry entry.

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

The registry record establishes that a Phase II study of dasatinib in advanced NSCLC was conducted as a single-group trial and terminated. It describes a planned investigation of whether ERK phosphorylation inhibition measured after ex vivo exposure to dasatinib differed between participants classified as progressors and non-progressors by RECIST. It also records a regimen of 140 mg orally every day with continuous dosing from Day #1.

The record does not establish the result of that planned comparison. It states that low accrual prevented completion of the analysis, with enrollment of 7 and a target accrual of 40. It reports no estimate of the difference in inhibition, no uncertainty interval, and no test result. The record therefore does not support a conclusion that inhibition was greater, smaller, or similar between progression categories.

The same caution applies to the secondary outcomes. Response, progression-free survival at 6 months, adverse events, and laboratory associations are listed as outcomes, but completed results for those endpoints are not reported in the registry record. The safety counts are descriptive, and the uncontrolled design supplies no comparator for judging relative safety or clinical outcomes.

More generally, a laboratory association with progression status would not alone demonstrate that the laboratory measure predicts future outcomes or explains disease behavior. Nor would observations in a single treated group establish what would have occurred without dasatinib or with another therapy. Those questions require appropriate measurement, complete outcome reporting, and a design and analysis suited to the intended inference.

The most defensible reading is therefore about study conduct and reporting: the trial sought to connect ex vivo target modulation with clinical progression categories, but the planned primary analysis was not completed as recorded. This is not evidence for or against a treatment effect. The reason for termination, full analysis plan, missing-data methods, and detailed results are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary objective joins a laboratory measure to a clinical progression classification. Translational studies often seek to determine whether a biological response to a compound corresponds to outcomes observed in patients. Such questions can be valuable for generating hypotheses about target modulation, but they require careful distinction between a measurable laboratory response, an association with clinical status, and a causal treatment effect.

The single-group design makes that distinction especially important. The planned progressor versus non-progressor comparison is not a randomized comparison of dasatinib against another treatment. Even if a difference in inhibition had been reported, it would have described an association between the laboratory measure and the progression categories in this study; it would not, by itself, establish that dasatinib caused a clinical response or that the measure could guide treatment decisions.

Accrual also matters directly to the feasibility of the planned inference. The registry states that 7 participants were enrolled, compared with target accrual of 40, and that this prevented completion of the analysis. This illustrates how an incomplete study can leave a scientifically motivated question unresolved. The record does not provide enough information to judge the intended precision or the reasons for the accrual target, but it clearly distinguishes the planned assessment from a completed result.

Finally, the registry entry shows why outcome listings, safety counts, and analytical findings must not be conflated. An outcome may be named without a result being reported; a safety count may describe observed events without establishing causation; and a planned laboratory comparison may remain unanswered. Keeping these distinctions explicit helps readers recognize both the value of a research question and the limits of the evidence recorded for it.

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 trial-specific limitation is that the primary analysis was not completed. The registry attributes this to low accrual, reporting enrollment of 7 against target accrual of 40. It does not report the number of participants in each progression category, the availability of ex vivo measurements, or any partial analysis. As a result, the primary objective cannot be evaluated from the registry record.

The study had no control group and no masking. Its single-group design does not permit a like-for-like comparison of dasatinib with another treatment. The planned comparison of progressors and non-progressors is a comparison across outcome categories, not a randomized contrast. The record does not report a statistical plan that would clarify the intended estimation method or how uncertainty would be assessed.

Important implementation details are also absent. Eligibility criteria, the exact method for measuring ERK phosphorylation inhibition, treatment exposure and adherence, follow-up procedures, handling of missing observations, analysis populations, and the reason for termination are not reported in the registry record. These gaps limit assessment of measurement quality, participant selection, and the interpretation of outcomes.

Although several secondary outcomes are listed, completed results and definitions are not reported in the entry. The safety information is descriptive and lacks a control group, event timing, and treatment attribution details. The registry record also does not report a multiplicity strategy or a sample-size justification. These limitations constrain conclusions about clinical outcomes, biological associations, safety comparisons, and the intended precision of the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dasatinib in Advanced Non-small Cell Lung Cancer (NSCL) With Ex Vivo and In Vivo Assessment of Tumor Target Modulation — NCT00858403.
• Registry record last updated 2014-01-15; status last verified 2013-12.
• Results first posted 2011-09-07.
• 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

The registry describes a Phase II, single-group study of dasatinib in advanced non-small cell lung cancer. The regimen was 140 mg orally every day with continuous dosing starting on Day #1. The study started in 2009-03, had primary completion recorded as 2010-07, and is listed as terminated.

The primary objective was to assess whether ex vivo ERK phosphorylation inhibition differed between participants classified as progressors and non-progressors by RECIST. The registry states that low accrual prevented completion of the planned analysis: enrollment was 7 against a target of 40. No completed primary comparison or secondary outcome analyses are reported in the registry record.

For the dasatinib group, the entry records 3 participants with serious adverse events among 7 at risk and 6 with other adverse events among 7 at risk. The design had no control group, and the record does not report the reason for termination, the statistical analysis plan, missing-data methods, or a completed analysis population.