Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy (NCT01938716), a na na study. The primary outcome is To Quantifiably Assess Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue After a Single Intraoperative Infusion in Patients..

2. Clinical Question

The central question is pharmacokinetic: whether the drug can be measured in tumor tissue after administration during surgery. This is different from a clinical efficacy question. The record does not define a comparison for assessing whether the infusion changes tumor growth, survival, or another clinical outcome, and it does not report a treatment-effect estimate. The listed secondary objectives concern DNA incorporation, possible markers of sensitivity or resistance, microvessel density, Hedgehog signaling, Ki67, and intratumoral apoptosis. These are planned biological measurements, not results. The registry record does not report their findings.

3. Trial Design

The registry lists this as a single-group, nonrandomized study with masking recorded as none and phase recorded as NA. Allocation is also recorded as NA. These entries indicate that the record does not describe random assignment or a masked comparison. The listed intervention is gemcitabine administered intravenously during surgery.

The arm description specifies 500 mg/m2 at a fixed dose rate of 10 mg/m2/min for the first 5 patients, with the stated purpose of validating hematologic safety. It then describes 750 mg/m2 at the same fixed dose rate for the next 15 subsequent patients. The registry enrollment is 12. The record does not establish how many participants received either dose, and the described dose sequence should not be treated as evidence that every planned dose cohort was completed. The infusion timing text is incomplete: it states that infusion started 50-75 minutes prior to complete, without completing the phrase.

The study began in 2012-03, and the primary completion date is listed as 2019-06-03. The status is terminated. The primary outcome timeframe is described as through study completion, up to 2 years and 6 months. The record identifies early termination due to low accrual as a reason relevant to the primary objective, but it does not give further details about the decision or timing of termination.

The design is suited to collecting tissue and blood measurements after an infusion, but it does not support a controlled treatment comparison. The registry record does not report a statistical analysis plan, allocation procedure, blinding beyond the masking entry, or a sample-size justification. A planning illustration based on the observed effect is not a substitute for those missing design details and should not be read as evidence of the study's planned power.

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: Samples inadequate for testing to meet objective; early termination of protocol due to low accrual.

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 To Quantifiably Assess Intratumoral Gemcitabine Levels in Human Pancreatic Cancer Tissue After a Single Intraoperative Infusion in Patients., measured over through study completion, up to 2 years and 6 months.

The primary outcome is intended to quantify intratumoral gemcitabine levels in human pancreatic cancer tissue after a single intraoperative infusion in patients who have received preoperative chemoradiation. The description states that gemcitabine concentrations in frozen cancer tissue, serum, and peripheral blood mononuclear cells would be assessed using standardized high-performance liquid chromatography-mass spectrometry techniques. The outcome timeframe is through study completion, up to 2 years and 6 months.

Drug measurement in tumor tissue addresses whether the administered drug can be detected at the intended site. Measurements in blood provide related pharmacokinetic information, while tissue measurements focus on delivery into the tumor. The registry also lists secondary biological questions about DNA incorporation and markers that might relate to sensitivity, resistance, delivery, or tumor activity. These objectives do not by themselves establish clinical benefit.

The endpoint description does not state a specific summary measure, such as a mean, median, range, or proportion above a threshold. No unit or dispersion measure is entered for the primary outcome, and no measured values or outcome analysis are reported in the registry record. The record also identifies inadequate samples for testing as a concern. Consequently, the objective is clear at a broad level, but the reported information does not permit readers to assess the magnitude or precision of any tissue concentration estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a pharmacokinetic measurement describe?

Pharmacokinetics concerns how a drug is present in the body over time and across sampled compartments. In this study, the stated objective is to quantify gemcitabine in tumor tissue, serum, and peripheral blood mononuclear cells after an intraoperative infusion. A concentration measured in a tissue sample is a direct laboratory observation in that sample. It is not automatically a measure of drug activity, tumor response, or clinical benefit.

Measuring several compartments can help distinguish drug detected in circulation from drug detected in the tissue of interest. However, interpreting such measurements requires details about specimen collection, assay performance, sample adequacy, timing, and the statistical summary used. The primary outcome description names the laboratory approach but does not report the measurement units, a summary statistic, dispersion, or results. The registry record also flags inadequate samples for testing as a concern, so the distinction between enrolled participants and participants with usable assays matters.

What does a single-group design allow?

A single-group design can describe measurements observed after an intervention in the enrolled group. It does not provide a concurrent untreated or alternative-treatment group. Without such a comparator, it cannot estimate a between-group treatment contrast. The registry identifies allocation as NA and the model as single group. It does not report random assignment, and masking is listed as none.

These design features do not invalidate a laboratory measurement objective, but they define what can be concluded. The study can, in principle, report measured concentrations after infusion. It cannot use its design alone to separate the effect of the infusion from all other factors that may influence the observed measurements. The registry record does not report an analysis designed to address such a causal comparison.

Why are summary measures and uncertainty important?

A point estimate compresses observed data into a summary, while a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. Wider intervals generally indicate less precision, and narrow intervals generally indicate greater precision. This is a general statistical explanation; the registry record does not report a primary concentration estimate or confidence interval to interpret.

For laboratory outcomes, the choice of summary can matter. Concentrations may be summarized in different ways depending on their distribution and the scientific question. A mean describes an arithmetic average; a median describes the middle observation. Measures of spread indicate how variable the measurements are. The record does not say which summary was used, if any, and does not provide the data needed to compare possible summaries. It would therefore be inappropriate to select one or infer a distribution from the stated objective alone.

How should the safety counts be read?

Adverse-event counts are descriptive counts within the recorded at-risk group. They do not by themselves indicate event severity, duration, relatedness, or whether events were repeated. Serious and other adverse events are separate registry categories. In this record, the serious-event count is 0 affected among 8 at risk; the other-event count is 8 affected among 8 at risk; deaths are listed as 0. The registry record does not list serious-event terms and does not provide the event details needed to explain the other-event count.

When the denominator is limited, event counts can be imprecise as indicators of underlying risk. More generally, a recorded count of zero does not prove that an event is impossible or that no event could occur in a broader population. Conversely, an affected count does not establish that the intervention caused every recorded event. The record does not report attribution information or an analysis comparing risks.

What does the sample-size illustration mean?

The planning illustration is explicitly described as computed from the observed effect rather than as the trial's own design. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. These are planning assumptions, not observations from this single-group study. They should not be interpreted as the original enrollment rationale, observed power, or evidence that a two-arm comparison occurred.

Sample-size calculations describe how many participants might be needed under specified assumptions to detect a particular effect with a chosen level of statistical power. They depend on the effect size, variability, design, and analysis assumptions. When calculations are based on an observed effect, they are illustrative and can be optimistic or unstable, particularly when the underlying estimate is uncertain. The registry record does not report a protocol sample-size justification, a planned power, or a statistical analysis plan. The illustration cannot fill those gaps.

What can be said about multiplicity?

The registry lists several secondary biological objectives in addition to the primary tissue-quantification objective. Testing multiple hypotheses can increase the chance of at least one apparently notable result if each is assessed without adjustment. A multiplicity strategy may control that risk, but it can also affect power for individual outcomes. The registry record does not report a prespecified multiplicity procedure, the number of planned statistical tests, or analysis results. No conclusion about adjustment or unadjusted testing can be drawn.

Overall, the methods information identifies the intended measurements and the broad design, while leaving important analytic details unreported. The absence of posted estimates means that precision, variability, and statistical significance cannot be assessed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary objective and several secondary biological objectives, including DNA incorporation, candidate markers of gemcitabine sensitivity or resistance, microvessel density, Hedgehog pathway expression, Ki67, and intratumoral apoptosis. Considering several outcomes raises a general multiplicity issue: when many hypotheses are tested, the chance of finding at least one apparently notable result can increase. Statistical plans may address this through prespecification or adjustment, but the registry record does not report a multiplicity strategy or identify which tests, if any, were performed.

The record lists no analyses, and it does not post primary or secondary outcome results. It does not report a statistical analysis plan, the analysis population, or a definition of which participants or samples were considered evaluable. The primary outcome description identifies inadequate samples and early termination due to low accrual as concerns. It does not give counts of missing samples, reasons for missingness by participant, or a method for handling missing measurements.

Missing laboratory measurements can affect the interpretation of a study if sample availability is related to participant characteristics, treatment, or the measurement itself. This is a general concern, not a claim that any particular pattern occurred in this study. Without details on sample disposition and analysis populations, readers cannot assess whether the available measurements represent all enrolled participants or a selected subset.

The registry record does not report whether any interim analyses were planned or conducted, or how analyses might have changed following termination. Those matters are not reported in the registry record. As a result, the posted information is insufficient to assess multiplicity control, missing-data handling, or the relationship between enrollment, evaluable samples, and analyses.

11. Safety Results

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

Deaths

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 safety record lists 8 participants at risk for serious adverse events, with 0 affected. For other adverse events, it lists 8 at risk and 8 affected. Deaths are listed as 0. These are registry counts, not a comparison between treatment groups, because the study is recorded as single group.

The record does not list serious adverse-event terms. It also does not provide the names, number, severity, timing, duration, or attribution of the other adverse events. The affected count therefore cannot be used to determine what occurred or whether an event was related to gemcitabine, surgery, the underlying cancer, or another factor. The record does not report those assessments.

A recorded count of 0 serious events should be read as no serious events recorded in the stated at-risk group, not as proof that serious events cannot occur. The other-event count describes the registry category and should not be treated as a measure of severity. These figures are limited by the information and denominators in the record and do not establish a comparative safety profile.

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

The registry record establishes that the study was designed to measure gemcitabine in pancreatic cancer tissue, serum, and peripheral blood mononuclear cells after an intraoperative infusion. It also reports a single-group design, enrollment of 12, a terminated status, and the listed safety counts. These details describe the objective and conduct as recorded; they do not answer whether a particular tissue concentration was achieved.

No primary outcome estimate, assay result, confidence interval, or statistical analysis is reported. The record therefore does not show the amount of gemcitabine detected in tumor tissue, how much measurements varied, or how precisely a concentration could be estimated. It does not report the number of adequate samples or the number included in any analysis. Low accrual and inadequate samples are identified as concerns, but their quantitative impact is not given.

The study's design also does not support a randomized comparison. There is no concurrent control group in the record, so the information cannot quantify a difference between gemcitabine and another treatment or no infusion. The stated secondary objectives are biological questions; they should not be mistaken for results or evidence of clinical benefit. No conclusions about tumor response, survival, or comparative effectiveness are reported.

The safety counts are similarly limited. They describe recorded events in the stated risk groups, but the event details and attribution are not reported. A count of zero serious events in the recorded group is not proof of no risk, and the other-event count alone does not explain what happened.

Accordingly, the registry record supports an account of what investigators set out to measure and what broad design they used, but it does not provide the results needed to judge the primary pharmacokinetic objective. The absence of results should not be interpreted as a positive or negative finding. It means that the registry record does not report the evidence needed to make that assessment.

13. Why This Trial Matters Statistically

This study raises a useful statistical distinction between measuring a biological quantity and evaluating a treatment effect. Quantifying gemcitabine in tumor tissue is a measurement objective. A careful analysis would need to describe the measured values and their variability, along with the number and characteristics of samples that could be assayed. Without those results, the objective cannot be assessed from the registry record.

The study also illustrates why enrollment and analyzable sample counts are not interchangeable. The registry lists enrollment of 12, while the primary outcome description notes inadequate samples and early termination due to low accrual. It does not report how many samples were suitable for testing or how many observations were analyzed. For laboratory studies, sample adequacy can directly shape the amount of information available, so reporting participant flow and assay availability is important for judging precision and potential selection effects.

The one-group design further clarifies the limits of inference. It can describe observed measurements in the treated group, but without a concurrent comparator it cannot estimate a treatment contrast. That limitation is separate from the laboratory objective: even a precise concentration estimate would not, by itself, demonstrate clinical benefit or comparative effectiveness.

Finally, the record lists multiple secondary biological objectives but does not report an analysis plan or multiplicity handling. This matters because multiple outcomes can create interpretive challenges, particularly when analyses are not fully described. The registry record therefore demonstrates the value of transparent reporting of assay results, analysis populations, uncertainty, missing samples, and prespecified methods. Those details are necessary to distinguish a clearly defined scientific aim from evidence that answers 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.

Several limitations are specific to the information recorded for this study. It is listed as terminated, and the primary outcome description cites low accrual and inadequate samples for testing. The registry does not quantify how these issues affected enrollment, sample availability, or the primary analysis. Although enrollment is listed as 12, the number of usable tumor, serum, or peripheral blood mononuclear cell samples is not reported.

The planned dose description refers to the first 5 patients and the next 15 subsequent patients, while the registry enrollment is 12. The record does not state how many participants received each dose, so the dose sequence cannot be reconstructed from the posted information. The infusion-timing description is also truncated after the phrase 50-75 minutes prior to complete, leaving its intended endpoint unclear.

The primary outcome has no reported unit or dispersion measure, and no results are posted. The record does not specify the summary statistic, sample-level assay results, handling of measurements below assay limits, or procedures for missing samples. It also does not report a statistical analysis plan, analysis population, multiplicity strategy, or sponsor analysis. These omissions prevent an assessment of measurement precision and analytic decisions.

The single-group design and absence of randomization mean that there is no concurrent control comparison. The safety record provides counts but not event terms for other adverse events or information on seriousness, timing, duration, or attribution beyond its categories. These limitations apply to interpretation of the registry record; they do not establish what additional information may exist outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Gemcitabine Pharmacokinetics After Preoperative Chemoradiation Therapy — NCT01938716.
• Registry record last updated 2020-11-05; status last verified 2020-10.
• Results first posted 2020-11-05.
• 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 record describes a single-group study of intraoperative intravenous gemcitabine in pancreatic cancer after preoperative chemoradiation. Its primary objective was to quantify gemcitabine in tumor tissue, with serum and peripheral blood mononuclear cell measurements also described. The record lists enrollment of 12, status as terminated, and no masking.

The primary outcome description identifies inadequate samples and early termination due to low accrual as concerns. No primary or secondary outcome results or analyses are reported in the registry record. The safety record lists 0 serious adverse events among 8 at risk, 8 affected by other adverse events among 8 at risk, and 0 deaths. Event details for the other adverse events are not reported.

The available information supports interpretation of the study's aims and broad design, but not an assessment of measured tissue concentrations, their precision, or clinical effects.