Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma (NCT02754726), a na phase 2 study. The primary outcome is Complete Response Rate.

2. Clinical Question

In practical terms, the trial was intended to characterize response and safety when the five drugs were given together in this clinical setting. The registry describes the primary endpoint as being assessed from enrollment until documented progression or death from any cause, with assessment up to 84 months. Its endpoint definition distinguishes complete response from partial response and overall response. Those are related but not interchangeable measures: the stated primary endpoint is complete response, while overall response combines complete and partial responses.

Because the study had no comparator group, it can describe outcomes observed among participants receiving the combination, but it cannot by itself establish how those outcomes compare with another treatment. The posted registry record does not include the primary response result or a reported comparative analysis. The question that can be addressed from the available record is therefore limited to the study’s design, endpoint definition, and reported adverse-event counts.

3. Trial Design

This was a phase II pilot trial for participants with previously untreated metastatic pancreatic ductal adenocarcinoma. The registry lists the study as completed and reports enrollment of 35. The study started in 2016-04, and its primary completion date is 2023-04-11. The sponsor was HonorHealth Research Institute.

The design was single-group, with no allocation to separate treatment arms and no masking. The arm description identifies an open-label combination therapy. All five listed interventions were drugs: nivolumab, albumin-bound paclitaxel, paricalcitol, cisplatin, and gemcitabine. Since the registry describes no concurrent control group, differences between treatment groups cannot be estimated from this trial.

The stated primary outcome was complete response rate, measured in participants. The endpoint description refers to RECIST v1.1 assessment of target lesions and includes confirmation requirements for a complete response. It also describes partial response and overall response, but the named primary outcome is complete response rate. The stated assessment period runs from enrollment until documented progression or death from any cause, with assessment up to 84 months.

The registry also lists treatment-related adverse events assessed using CTCAE v4.0 as a secondary outcome. It reports counts for serious and other adverse events and lists serious adverse-event terms. The record does not provide the detailed statistical analysis plan, the criteria for inclusion in each analysis population, or a rationale for the enrollment target. Those details are not reported in the registry record. The absence of a posted analysis does not establish what analyses may have been conducted outside the registry.

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: Not evaluable for overall response as subject did not have post baseline scans (n=3)

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 Complete Response Rate, measured over From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 84 months.

The primary endpoint is complete response rate, expressed as a count of participants in the registry description. A complete response is defined using RECIST v1.1 criteria as disappearance of all target lesions with no new sites or disease-related symptoms. The description also requires confirmation at least 4 weeks after the initial documentation and specified tumor-marker values to be down to normal limits. It says a PET scan will be obtained to confirm a documented complete response.

The endpoint is used to describe whether participants meet the stated criteria for complete disappearance of target disease findings during follow-up. Such a defined endpoint makes response assessment more consistent than an informal judgment, although its interpretation still depends on the assessment process and the availability of follow-up scans. The registry description notes that participants without post-baseline scans were not evaluable for overall response; it does not state how those participants were handled in the primary complete response analysis.

The endpoint description also defines partial response as at least a 30% decrease in the sum of target-lesion diameters and overall response as complete response plus partial response. These definitions provide context but do not change which outcome is named primary. The posted registry record does not report the observed complete response count or rate. It therefore does not support a numerical statement about the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described are bounded by the registry record. It identifies a phase II pilot trial with a single-group, open-label design. It names the primary endpoint and describes how response was to be assessed. It does not report the statistical analysis plan, the primary response count, or a posted analysis result. Any explanation of statistical concepts below is general, rather than a claim about methods used in this trial.

What does a single-group design permit?

A single-group study follows participants receiving the study regimen without a concurrent comparison group. It can describe outcomes observed in the group, provided those outcomes and their analysis are reported. It cannot estimate a randomized treatment contrast because no group was assigned a different treatment. Even when an observed outcome is available, changes over time or response during treatment cannot, by themselves, separate the effect of the regimen from other explanations. This is why the design should be read as descriptive rather than as a controlled comparison.

The registry lists no allocation and no masking. In general, open-label assessment means treatment assignment is not concealed from participants or study personnel. For an imaging-based endpoint, a prespecified response definition can help standardize classification, but the record does not say whether assessors were independently blinded or how disagreements were handled. Those procedures are not reported in the registry record.

What does the response definition contribute?

RECIST v1.1 supplies the stated framework for assessing target lesions. The record defines complete response as disappearance of all target lesions with no new sites or disease-related symptoms, and requires confirmation at least 4 weeks after initial documentation. It also describes marker requirements and says a PET scan will be obtained to confirm a documented complete response. These rules make clear that a single observation of lesion disappearance is not, by itself, the full stated definition. The registry does not report the actual assessment schedule beyond the overall follow-up description, nor does it report how the criteria were applied to individual participants.

A complete response is narrower than overall response in the record’s definitions. Partial response is defined as at least a 30% decrease in the sum of target-lesion diameters, and overall response is defined as complete response plus partial response. Since the primary endpoint is complete response rate, a partial response should not be counted as a complete response when interpreting that endpoint. The numerical counts for these response categories are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under the assumptions of the analysis. Its width conveys precision: a wider interval indicates less precision than a narrower interval. A point estimate without an interval does not show how uncertain that estimate is. No primary response estimate or confidence interval is reported in this registry record, so there is no basis for describing the precision of the primary endpoint.

In general, a p-value is a measure calculated under a specified statistical model and null hypothesis. It is not a measure of clinical importance and does not replace an effect estimate with an uncertainty interval. The registry record does not report p-values or an inferential analysis for the primary endpoint. The trial’s single-group design also means that a p-value cannot create the missing concurrent treatment comparison.

What do the adverse-event counts describe?

The registry reports affected and at-risk counts for serious and other adverse events. These are descriptive counts for the single arm, not estimates of comparative risk. The serious adverse-event terms are listed with percentages, but the record does not describe the calculation method for each term or provide a comparison group. General statistical interpretation of event counts should distinguish the number of participants with an event from the number of events, since an individual may experience more than one event. The registry’s figures are described as participants affected; they should not be read as event totals unless the record says so.

In general, adverse-event rates may be difficult to interpret when follow-up time differs across participants or when definitions and ascertainment vary. The record states that treatment-related events were assessed using CTCAE v4.0, but it does not provide participant-level follow-up time, exposure duration, or detailed rules for attributing an event to treatment. Those limitations prevent a more detailed rate interpretation.

What is not available about the analysis?

The registry record does not report the analysis population, missing-data approach, prespecified statistical model, or handling of multiple outcomes. It also does not provide a sample-size justification. The presence of a planning illustration elsewhere does not establish the trial’s original design assumptions; the record’s sample-size assumptions describe an illustration based on an observed effect, not the trial’s own design. No recalculated efficacy estimate is available in the record. Without the underlying outcome results and analysis specification, readers should not infer an analysis method or reconstruct an endpoint result.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies complete response rate as the primary outcome and lists treatment-related adverse events as a secondary outcome. It also describes partial response and overall response in the definition of the primary endpoint, but that does not make them reported primary results. The record does not state how many outcomes were prespecified in the protocol, how multiple outcomes were prioritized, or whether any adjustment for multiple statistical tests was planned. Multiplicity procedures are therefore not reported in the registry record.

Multiplicity matters in general when several outcomes or analyses are tested: the chance of finding an apparently notable result can depend on how many opportunities were considered. An adjustment or a clear hierarchy can address that issue, but neither can be assumed. Since the record does not post the primary response result or inferential analyses, there is no basis to evaluate how multiplicity affected reported efficacy findings.

Missing response assessment is explicitly noted for 3 participants, who were described as not evaluable for overall response because they had no post-baseline scans. The record does not say whether this same evaluability rule applied to the complete response endpoint, whether missing responses were counted as nonresponses, or whether another approach was used. The analysis population and missing-data handling are not reported in the registry record. It would be inappropriate to select a denominator or impute outcomes from the enrollment count.

The record does not identify intention-to-treat, per-protocol, or safety populations, or explain which participants were included in each outcome analysis. These labels should not be assigned based on assumption. The posted information supports noting the reported enrollment and the stated non-evaluable status, but not reconstructing the analysis set or the treatment of missing observations.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: colitis (8.6%), dehydration (5.7%), fatigue (5.7%), lung infection (5.7%), sepsis (5.7%).

The registry reports serious adverse events for 35 participants at risk, with 14 affected. It separately reports other adverse events for 35 participants at risk, with 35 affected. These are participant counts in the single arm, not a comparison with another regimen. The record lists serious adverse-event terms including colitis at 8.6%, and dehydration, fatigue, lung infection, sepsis, and thromboembolic event at 5.7% each.

The listed terms should be read as the registry’s reported serious-event entries, not as a complete account of every safety outcome. The record does not provide a comparative group, event-level detail, participant follow-up time, or the statistical method behind these percentages. Because a participant can experience more than one type of event, the term-specific entries should not be added together to infer a total number of affected participants.

The registry also lists 1 death. It does not give enough detail in the record to determine the cause or relationship of that death to treatment. These safety figures describe what is recorded for this study group; without comparative data, they cannot establish whether the regimen changes the frequency of adverse events relative to another approach.

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

This trial record describes a completed phase II pilot study of a five-drug combination in previously untreated metastatic pancreatic ductal adenocarcinoma. It provides a defined primary response endpoint and some safety counts. Those details are useful for understanding what the investigators intended to measure and what adverse-event information was posted.

The central efficacy result is not reported in the registry record. The complete response count and rate are unavailable, as are an uncertainty interval and the analysis method. The record therefore does not allow a reader to quantify the primary outcome or assess its precision. The noted participants without post-baseline scans further underscore that the evaluable population and handling of missing response data matter, but those analytic details are not provided.

The observed adverse-event counts are descriptive. In a single-group study, they cannot show how the same participants would have fared under a different treatment. Nor do the reported counts establish that an event was caused by the combination; the registry labels the secondary outcome as treatment-related, but does not provide enough detail to evaluate individual attribution.

These limits do not make the registry information uninformative. The design, response criteria, follow-up description, and adverse-event entries help readers understand the scope of the study record. They do mean that conclusions should remain proportionate to what is reported. The record does not establish comparative effectiveness, does not provide the primary response result, and does not support a causal interpretation of the listed safety events. Additional analyses or reports may exist, but they are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a narrowly defined response endpoint with a single-group design and an incomplete posted efficacy result. That combination makes it especially important to distinguish the endpoint’s clinical definition from the evidence available to estimate it. RECIST v1.1, confirmation requirements, and the stated tumor-marker conditions clarify what would count as a complete response; they do not substitute for a reported response count or rate.

The study also illustrates why evaluability and analysis populations matter. The registry notes participants without post-baseline scans, but does not describe how those observations affected the primary analysis. A response estimate can depend on who is included and how missing assessments are handled. Without that information, readers cannot reconstruct a denominator or judge possible bias from incomplete assessment.

Its single-group structure places a clear boundary on inference. Even a fully reported response frequency would describe outcomes in participants receiving the combination, not a treatment contrast against a concurrent control. The same distinction applies to the adverse-event counts: they provide a safety description for the study group, not comparative evidence.

Finally, the record offers a useful reminder that completion status and outcome availability are different. A study may be listed as completed while important results and statistical details remain unreported in its registry entry. Clear reporting of response counts, analysis populations, missing-data handling, and uncertainty would be needed to support a fuller statistical interpretation. Those details are not reported in the registry record.

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 limitation for interpreting efficacy is that the registry record does not report the primary complete response count or rate. It also provides no confidence interval, p-value, or analysis method for that endpoint. The primary result’s precision and the extent to which it depends on analytic choices therefore cannot be assessed.

The record notes that 3 participants were not evaluable for overall response because they lacked post-baseline scans. It does not specify the primary endpoint denominator, the response status assigned to participants without scans, or whether the same evaluability designation applied to complete response. This prevents reconstruction of the response analysis and leaves the handling of missing assessments unclear.

The single-group, open-label design has no concurrent comparator. It can describe the study group but cannot provide a controlled estimate of how outcomes differ from another treatment. The registry does not report details of response assessor masking or adjudication, so the safeguards used to limit assessment bias are unknown.

Safety interpretation is also limited. The registry gives affected and at-risk counts, listed serious-event terms, and a death count, but not a comparative group, detailed event-level data, exposure duration, or enough context to establish causality. The analysis populations, multiplicity approach, protocol-based statistical plan, and sample-size justification are not reported in the registry record. These limitations are specific to the information available in this trial entry and should not be filled by assumptions about the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combination Therapy for Patients With Untreated Metastatic Pancreatic Ductal Adenocarcinoma — NCT02754726.
• Registry record last updated 2025-08-27; status last verified 2025-08.
• Results first posted 2024-12-10.
• 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

NCT02754726 is a completed phase II pilot trial sponsored by HonorHealth Research Institute. It enrolled 35 participants with previously untreated metastatic pancreatic ductal adenocarcinoma and used a single-group, open-label design. The combination included nivolumab, albumin-bound paclitaxel, paricalcitol, cisplatin, and gemcitabine.

The primary endpoint was complete response rate, assessed using RECIST v1.1 criteria and additional confirmation requirements. The registry record does not report the primary response count or rate. It notes 3 participants were not evaluable for overall response because they had no post-baseline scans. The record reports serious adverse events in 14 of 35 participants at risk and other adverse events in 35 of 35 participants at risk, and lists 1 death.

The study started in 2016-04, with primary completion dated 2023-04-11. Statistical analysis details, the response analysis population, and missing-data handling are not reported in the registry record.