Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer (NCT02775695), a na phase 2 study. The primary outcome is Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response.

2. Clinical Question

This is a window-of-opportunity question: treatment is given before surgery, and tissue from the resected tumor is used to assess a biological response. The registry describes metakaryotes as cancer stem cells in its brief summary. The primary endpoint focuses on a count in tumor tissue rather than a clinical outcome such as survival or symptom change.

The distinction between the study question and the available evidence is important. The registry specifies the biological measurement, treatment, and assessment timing, but it does not provide a numerical result for the cell count or an analysis of the endpoint. Consequently, the record describes what the trial was intended to investigate, not whether the observed tumor measurement changed or how precisely any effect was estimated.

3. Trial Design

The registry identifies NCT02775695 as a completed phase 2 study sponsored by the Medical College of Wisconsin. The recorded start date is 2017-04-03, and the primary completion date is 2018-09-25. Enrollment is listed as 12. The condition is resectable pancreatic cancer, and the intervention is doxycycline.

The design is recorded as single-group, with allocation listed as NA and masking listed as none. The arm is titled Doxycycline Administered to Patients. Its description says patients would receive oral doxycycline and have trough serum concentrations obtained for pharmacokinetic studies. The brief summary characterizes the study as a window-of-opportunity study examining doxycycline after eight weeks of treatment. These registry entries describe the planned intervention and design; they do not establish how many participants completed treatment, had surgery, or contributed an endpoint measurement.

The primary outcome is a continuous measure reported as a mean with standard deviation, in Cells/g, at the Month 3 visit. The description says histopathologic response would be assessed using College of American Pathology criteria for residual tumor response following neoadjuvant therapy for the exocrine pancreas, and that researchers would enumerate observed dead or dying metakaryotes per gram of resected tissue.

Because there is no control group, the design cannot directly compare doxycycline with an untreated or alternative-treatment group. The registry record does not report a protocol-level explanation for the sample size, details of interim analyses, or a statistical analysis plan. Completion status indicates the trial is recorded as completed; it does not itself provide evidence about the primary outcome or the conduct of the analysis.

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

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 Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response, measured over Month 3 visit.

The primary endpoint is the number of observed dead or dying metakaryotes per gram of resected pancreatic tissue, measured at the Month 3 visit. The registry describes this as a measure of doxycycline’s efficacy in inducing metakaryotic cell death in primary pancreatic tumors. It also says the histopathologic response would be assessed using College of American Pathology criteria for residual tumor response after neoadjuvant therapy for the exocrine pancreas.

This endpoint is a tissue-based biological measure. It focuses on a tumor characteristic after the planned treatment period rather than on a patient-centered clinical outcome. Counting dead or dying cells in resected tissue can help characterize a biological response in the tumor, while the unit Cells/g indicates that the count is expressed relative to tissue mass. The registry classifies the outcome as continuous and specifies a mean and standard deviation as its summary parameters.

The endpoint’s meaning depends on how the cells were identified and counted, how tissue was sampled, and how measurements were summarized. The registry description names the cell count and histopathologic criteria, but does not report operational details for counting or a numerical result. It also does not report whether the measurement was available for all enrolled participants. Therefore, the endpoint definition can be described, but its observed value and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as continuous, with the mean and standard deviation as the reported summary statistics. The measurement itself is a count of observed dead or dying metakaryotes per gram of resected tissue. A mean describes the arithmetic center of observed values, while a standard deviation describes their spread around that center. These summaries can be useful for communicating a group’s measurements, but the registry record does not report the values for this endpoint.

What would a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimate under a specified statistical model. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the method and assumptions used to calculate it. For a treatment-effect estimate, an interval can show both the range of values reasonably compatible with the observed data and the precision of the estimate. The registry record does not report a confidence interval for the primary endpoint, so its precision cannot be assessed.

A confidence interval for a single-group mean would address uncertainty about that group’s mean, not the difference between doxycycline and a comparator. To estimate a comparative treatment effect, the study would need a valid comparison and a defined contrast. This trial is recorded as single-group, and no comparator is described. A single-group mean, even if it were reported, would not by itself separate a treatment effect from other explanations for the observed value.

Why does the endpoint’s distribution matter?

General statistical consideration: count measurements often have a different distribution from measurements that can take a broad range of continuous values. Counts are nonnegative and may be skewed, and their variability can depend on their average level. Expressing a count per gram sets a tissue-mass basis for the measurement, but does not by itself establish that the resulting values follow a normal distribution. The registry labels the outcome continuous and specifies mean and standard deviation; it does not report the distribution of the measurements or the model used to analyze them.

General statistical consideration: over-dispersion occurs when count data vary more than a chosen count model expects. If over-dispersion is present but not handled, standard errors may be too small and statistical evidence may appear more precise than it is. A suitable analysis would depend on the observed data, measurement process, and prespecified plan. The registry record does not report a model, a check for over-dispersion, or an analysis plan, so it is not possible to say whether this issue arose or how it was addressed.

What does the single-group design permit?

A single-group study can describe measurements among participants who receive the intervention. It cannot make a direct randomized comparison when there is no control arm. Changes in a biological measure may reflect the intervention, but may also reflect the natural course of disease, other care, variation in tissue sampling, or measurement procedures. These are general possibilities, not reported findings in this trial. The registry record does not describe a baseline measurement for the primary endpoint or an analysis comparing baseline with the post-treatment tissue measurement.

The absence of masking is recorded as none. In general, unmasked measurement may be more vulnerable to influence from knowledge of treatment or clinical context, depending on how an outcome is assessed. The registry describes a histopathologic assessment and cell enumeration, but does not report whether assessors were blinded, what procedures were used to limit measurement bias, or how reproducibility was evaluated. Those details are not reported in the registry record.

How should the planning illustrations be read?

The stated planning setup uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are assumptions for planning illustrations, not a description of this trial’s single-group design. The illustrations are not observed power and do not show that the trial had a particular probability of detecting an effect. A planning calculation is conditional on its assumed effect, variability, significance level, allocation, and analysis method.

Because the registry record does not report the primary endpoint estimate or an analysis, the observed effect underlying such an illustration cannot be evaluated from the registry record. The planning assumptions also do not turn a single-group result into a comparative estimate. Any displayed participants-per-arm figures are hypothetical planning quantities under the stated two-arm assumptions, not the number enrolled in this study and not evidence about what the trial observed.

More generally, interpretation of an analysis depends on the target estimand, the analysis population, treatment exposure, endpoint availability, and the handling of missing measurements. Those details are not reported in the registry record. The record does identify the proposed endpoint, summary type, unit, and timeframe, but does not give the analysis methods needed to assess whether the intended question was answered or how uncertainty was quantified.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Doxycycline Administered to Patients")
n   <- c(12)
m   <- c(8.9)
sp  <- c(7.25)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Doxycycline Administered to Patients  12  8.900  7.250  4.294  13.506

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analysis results. It does not report a prespecified statistical analysis plan, a strategy for controlling multiplicity, or whether additional outcomes were analyzed. Without these details, it is not possible to assess whether testing across multiple outcomes, time points, or subgroups affected interpretation. The presence of a single listed primary outcome does not establish that no other analyses were conducted.

Missing-data handling is also not reported in the registry record. The record does not state how many participants had tissue available for the primary endpoint, how unavailable or inadequate samples were handled, or whether any measurements were excluded. It does not report an analysis population definition, such as an intention-to-treat or evaluable-participant population. Enrollment of 12 should not be read as confirmation that all enrolled participants contributed a primary endpoint measurement.

These omissions matter because the number and characteristics of participants with evaluable tissue can affect the meaning and precision of an endpoint estimate. In general, methods for handling missing outcomes require assumptions about why data are missing; different assumptions can lead to different interpretations. No such assumptions or sensitivity analyses are reported in the registry record. Consequently, the extent to which missing measurements could influence the primary endpoint cannot be determined.

The trial is recorded as completed, but completion status does not resolve questions about analysis populations, missing measurements, or multiplicity. Those details would be needed to evaluate the statistical analysis more fully.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal disorders - other, specify (16.7%), anaphylaxis (8.3%), abdominal pain (8.3%), ascities (8.3%), diarrhea (8.3%).

The registry records serious adverse events for the Doxycycline Administered to Patients group. Serious adverse events affected 9 of 12 participants at risk. Other adverse events affected 11 of 12 at risk, and deaths were recorded as 0. These are descriptive counts for the registered group. The record does not provide a comparator group, so the counts cannot be interpreted as comparative risks.

The listed top serious adverse event terms are Gastrointestinal disorders - other, specify at 16.7%, Anaphylaxis at 8.3%, Abdominal pain at 8.3%, Ascities at 8.3%, Diarrhea at 8.3%, and Nausea at 8.3%. These percentages should be read as registry-reported term summaries. They are not a treatment-versus-control comparison, and they do not by themselves establish that an event was caused by doxycycline. The registry record does not provide event-level timing, duration, outcome, or a detailed attribution assessment.

Counts of affected participants and counts by event term are different kinds of summaries. A participant may have more than one event, so event-term counts should not be added to infer the number of affected participants. The serious-event and other-event figures also should not be combined into a new total. The record does not report additional detail needed to interpret overlap among event categories.

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

The registry record describes a completed phase 2, single-group study of oral doxycycline in patients with resectable pancreatic cancer. Its primary question concerns dead or dying metakaryotes in resected pancreatic tissue after the planned treatment period. The recorded endpoint is a cell count per gram, with a Month 3 visit listed as the timeframe. This identifies the biological measurement the study set out to assess.

The record does not report the primary endpoint’s observed mean, standard deviation, or any statistical analysis. It therefore does not show how many dead or dying metakaryotes were observed, how variable the measurements were, or how precise an estimate might be. It cannot establish from the registry information whether the endpoint changed or whether any change was associated with doxycycline.

The single-group design also limits causal interpretation. There is no comparator group described, so the registry does not provide a direct estimate of how the outcome under doxycycline differs from an outcome under another treatment or no treatment. A biological measurement in a treated group can be descriptive, but it cannot by itself rule out other explanations for the observed measurement. The registry record does not provide a baseline endpoint measurement or a comparative analysis.

The safety counts show serious adverse events affecting 9 of 12 at risk, other adverse events affecting 11 of 12 at risk, and deaths recorded as 0. These figures describe the registered group and are not comparative estimates. They do not establish event attribution, and the listed adverse event terms do not substitute for a full account of event timing and clinical context.

Thus, the registry information supports a careful description of the trial’s intent, design, endpoint, and recorded safety summaries. It does not support a conclusion about the efficacy of doxycycline or a conclusion that it did or did not induce the specified cell death. Those conclusions would require outcome results and adequate analysis information that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between measuring a biological response and estimating a treatment effect. The primary endpoint is a tissue-based count intended to describe dead or dying metakaryotes in a resected tumor. Such a measurement can address a mechanistic question, but its interpretation depends on how cells are identified, how tissue is sampled, and how the observations are summarized. The registry record defines the broad measure and unit but does not report detailed measurement procedures or endpoint results.

The design also illustrates why a clearly defined endpoint does not, by itself, establish causality. The registry identifies a single-group study with no comparator. A value measured after treatment can describe the treated group, but a comparison is needed to estimate how outcomes differ under alternative treatment conditions. Without a comparator or a reported baseline analysis, it is not possible to attribute an observed value to the intervention from the registry information alone.

The endpoint is recorded as continuous and summarized by a mean and standard deviation, while its description is a count per gram of tissue. This makes distributional assumptions worth considering. General statistical practice would examine the measurement’s distribution and variability before selecting or assessing an analysis method. The registry record does not report the analysis method or those diagnostics, so no conclusion about their adequacy can be drawn.

Finally, the record highlights the importance of reporting more than design and outcome definitions. An estimate, an uncertainty measure, the analysis population, and an account of missing measurements are needed to assess how informative the trial’s result is. Here, those primary endpoint analysis details are not reported in the registry record. The distinction between planned measurement and reported evidence is central to interpreting this study statistically.

15. 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 direct limitation for interpretation is that the registry record does not report the primary endpoint result or an analysis. There is no reported mean, standard deviation, treatment-effect estimate, confidence interval, or test result for the cell count. As a result, the intended biological outcome cannot be evaluated quantitatively from the registry record.

The single-group design offers no concurrent comparator. Even if an endpoint estimate were available, the design as recorded would not provide a direct treatment contrast. The registry also does not report a baseline measurement for the primary endpoint or a before-and-after analysis. The effect of treatment therefore cannot be separated from other possible explanations on the basis of the registered design alone.

Details needed to judge measurement quality are not reported in the registry record. These include cell-identification and counting procedures, tissue-sampling procedures, assessment reproducibility, and whether endpoint assessors were blinded. The outcome is described as cells per gram, but the registry does not report the distribution of observed measurements or the statistical model used to analyze them.

The record does not state how many participants contributed an evaluable tissue measurement, how missing or unsuitable specimens were handled, or how the analysis population was defined. It also does not report a statistical analysis plan, multiplicity procedures, or interim analyses. Enrollment and completed status do not resolve those questions.

Safety information is also limited to registry summaries. Event timing, duration, outcome, attribution, and overlap among event terms are not reported. Because the study has no comparator group, the safety counts do not estimate comparative risk. These limitations concern what can be learned from the registry record; they do not establish what occurred beyond the information recorded there.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer — NCT02775695.
• Registry record last updated 2023-07-03; status last verified 2023-06.
• Results first posted 2023-07-03.
• 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.

19. Record Summary

NCT02775695 is recorded as a completed phase 2, single-group study sponsored by the Medical College of Wisconsin. It enrolled 12 patients with resectable pancreatic cancer and studied oral doxycycline in a window-of-opportunity setting. The brief summary describes eight weeks of treatment, and the primary endpoint timeframe is the Month 3 visit.

The primary endpoint is the number of observed dead or dying metakaryotes per gram of resected pancreatic tissue, summarized as a mean with standard deviation. The registry record does not report a numerical primary endpoint result or analysis. It lists serious adverse events affecting 9 of 12 at risk, other adverse events affecting 11 of 12 at risk, and deaths of 0. These safety summaries are descriptive and have no comparator group.

The record establishes the study’s intent and broad design, but does not provide enough endpoint or analysis information to assess efficacy, precision, missing data, or comparative safety.