Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma (NCT02551991), a na phase 2 study. The primary outcome is Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT).

2. Clinical Question

Although the study title describes a comparison with nab-paclitaxel plus gemcitabine, the registry record explains that the comparative part was not initiated. The results described in the clinical study report concern the single-arm dose exploration and dose expansion in Part 1. They therefore address tolerability and preliminary efficacy of the nal-IRI-containing regimen in this study setting, rather than a relative treatment effect against the regimen named as comparator in the title.

The registry lists secondary outcomes including progression-free survival, overall survival, best overall response, overall response rate, disease control rate, and duration of response. Numerical results for those outcomes are not reported in the registry record. Numerical results for the primary DLT endpoint are also not reported in the registry record, so the clinical question can be described but the endpoint result cannot be interpreted from this record.

3. Trial Design

This was a phase 2, open-label study sponsored by Ipsen. The registry lists an enrollment of 56 and identifies pancreatic cancer as the condition. The study start date is 2015-10-19, and the primary completion date is 2021-02-15. Its status is recorded as completed.

The original study plan described two parts. Part 1 included dose exploration, designated Part 1A, followed by dose expansion, designated Part 1B, for nal-IRI with 5-FU/LV and oxaliplatin. Part 2 was intended to compare an irinotecan liposome injection-containing regimen with nab-paclitaxel plus gemcitabine. The registry states that a protocol amendment dated 11 April 2018 removed the comparative Part 2 before it was initiated. The comparative question was being undertaken as a stand-alone phase III study, while the clinical study report for this record pertains to Part 1.

The record identifies the allocation as not applicable and the model as single group. It also identifies masking as none, consistent with an open-label design. There is no randomized control group in the analyzed Part 1 results. The dose exploration cohorts and dose expansion cohort are therefore not interchangeable treatment arms in a randomized comparison; they are cohorts within a dose-finding and expansion study.

The registry record does not report a detailed allocation procedure, a statistical analysis plan, or a sample-size justification. Those details should not be inferred from the phase, enrollment, or cohort labels. The number of participants recorded as enrolled describes the study record and does not itself supply the number included in each endpoint analysis. Endpoint-specific analysis populations and results are not reported in the registry record.

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: This study was divided into 2 parts: Part 1 (dose exploration \[Part 1A\] followed by dose expansion \[Part 1B\] of the irinotecan liposome injection + 5 fluorouracil \[5-FU\]/leucovorin \[LV\] + oxaliplatin regimen) and Part 2 (comparison of irinotecan liposome injection-containing regimen versus \[vs\] nab-paclitaxel plus gemcitabine). Overall, 56 participants were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included participants who received at least 1 dose of any study treatment.

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.

Population: Safety population included participants who received at least 1 dose of any study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT), measured over From the start of the first study treatment (Cycle 1 Day 1) up to 14 days after the second dose of study treatment, maximum of 42 days.

The primary endpoint is the number of participants with dose-limiting toxicities in Part 1A. A DLT was an adverse event occurring during the safety evaluation period and judged related to the study treatment regimen. An adverse event attributed to disease progression was not considered a DLT. The endpoint is a participant count, rather than a measure of how many total adverse-event episodes occurred.

The safety evaluation period was defined as 28 days of Cycle 1, or 14 days after the second dose if treatment was delayed. The stated overall timeframe runs from the start of the first study treatment, Cycle 1 Day 1, up to 14 days after the second dose, with a maximum of 42 days. This defined observation window focuses the DLT assessment on early treatment tolerability during dose exploration.

In general, a DLT endpoint can help guide dose selection by identifying treatment-related toxicities in a prespecified period. It is not a complete account of all safety events over the course of treatment, and it does not measure efficacy. Interpreting a participant count also requires knowing the relevant cohort denominator and the assessment rules applied to each participant. The registry record describes the endpoint and its population but does not report the observed DLT count or the corresponding denominator for Part 1A. The endpoint result is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine what statistical conclusions can reasonably be drawn. This study’s analyzed Part 1 is described as single-group and non-comparative. Its dose exploration and expansion cohorts are useful to describe within-study safety experience, but they do not create the randomized contrast needed to estimate a treatment effect against an active control. The comparative Part 2 named in the original study plan was removed before initiation.

What does a participant count represent?

The primary endpoint is a count of participants who experienced at least one qualifying DLT during the defined safety window. It is not a count of all adverse events, because one participant can experience multiple events. It is also narrower than overall safety: an event must occur in the evaluation period and be considered related to the regimen, while an event related to disease progression is excluded by the endpoint definition.

For a binary participant outcome, a count is ordinarily interpreted alongside the number of participants evaluated. The denominator clarifies how many people were at risk of meeting the endpoint, while the numerator records how many did. A proportion can then be presented with an uncertainty interval to show how imprecisely the underlying event frequency is estimated. The registry record does not report the Part 1A DLT count, endpoint denominator, proportion, or confidence interval. No such value can be inferred from the serious adverse event counts, because serious adverse events and protocol-defined DLTs are different outcomes.

Why does the study structure matter?

Dose exploration studies are designed to describe experience across regimen cohorts and inform further study, rather than to establish a randomized comparison. Cohort counts can differ because of cohort size, dose selection, participant characteristics, exposure, or chance. Without a randomized comparator and appropriate analysis, a difference between two cohort counts is descriptive and does not isolate the effect of a treatment difference.

Open-label conduct means treatment was not masked. The registry records no masking. In general, lack of masking can influence event reporting, clinical assessment, and decisions about whether an event is related to treatment. The DLT definition includes a judgment of relation to the regimen, so such judgments are relevant to interpretation. The registry does not report procedures for blinded event review or adjudication; whether such procedures were used is not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes the range of values reasonably compatible with the data under a specified statistical method. It conveys uncertainty around an estimate; it does not guarantee that the true value lies in the interval, nor does it account for every source of bias. For a small cohort, an event proportion can be imprecise even when reported as a simple percentage. Since the registry does not report DLT estimates or confidence intervals, the precision of the primary endpoint cannot be evaluated from this record.

The serious adverse event figures are counts and term percentages. They provide descriptive information, but the record does not supply comparative models, adjustment variables, or confidence intervals for these summaries. No inferential conclusion should be attached to numerical differences between cohorts. Serious event counts also do not substitute for a full event-level safety analysis, because the registry summary does not specify onset, duration, severity grading, treatment exposure, or participant-level overlap across event terms.

What do planning illustrations mean?

Any sample-size values presented with the posted results are planning illustrations based on an observed effect, not observed power and not the study’s original design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the planning target is a stated fraction of the observed effect. For time-to-event outcomes, such illustrations use a total event count, while other outcomes use participants per arm. These are general planning calculations and cannot convert this single-group Part 1 study into a randomized comparison. The trial’s own sample-size justification is not reported in the registry record.

The registry record lists no analyses for the outcomes in its analysis listing. The particular statistical procedures used for the clinical study report, including any adjustments, model choices, or handling of censoring, are not reported in the registry record. Consequently, it is not possible to reproduce or assess the statistical analysis from the registry summaries alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Dose Exploration: Cohort 1", "Dose Exploration: Cohort -1", "Dose Exploration: Cohort -2B", "Dose Exploration: Cohort -3")
n      <- c(7, 7, 10, 7)
events <- c(2, 1, 2, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dose Exploration: Cohort 1  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1
ARM  Dose Exploration: Cohort -1  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  Dose Exploration: Cohort -2B  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8
ARM  Dose Exploration: Cohort -3  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes alongside the primary DLT endpoint. Assessing several outcomes creates a multiplicity issue: when many statistical tests are conducted, the chance of at least one apparently notable result can increase. In general, a prespecified testing hierarchy or multiplicity adjustment can address this concern, but it is not possible to determine whether either was used. Multiplicity procedures and a detailed statistical analysis plan are not reported in the registry record.

The registry identifies the safety population as participants who received at least one dose of any study treatment. It does not report endpoint-specific analysis populations for the DLT endpoint or secondary outcomes. The number enrolled is recorded as 56, but that overall enrollment figure does not establish how many participants contributed to each analysis, completed follow-up, or had evaluable outcome data.

Missing-data methods are not reported in the registry record. For a time-to-event outcome, general methods may address incomplete follow-up through censoring rules; for a binary outcome, analysts may need rules for participants whose outcome status is unknown. Which approaches were used, and how missing observations affected results, cannot be determined from the registry information.

The registry record also does not report interim analyses, stopping rules, or sample-size justification. These omissions limit assessment of whether outcome selection, follow-up, or analysis decisions could affect interpretation. They should be treated as unreported methodological details, not as evidence that a particular procedure was or was not used.

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: abdominal pain (42.9%), diarrhoea (28.6%), colitis (28.6%), vomiting (20.0%), small intestinal obstruction (14.3%).

The serious adverse event summaries report the number affected and the number at risk in each cohort. The listed counts are 6 of 7 for Dose Exploration: Cohort 1, 2 of 7 for Dose Exploration: Cohort -1, 7 of 10 for Dose Exploration: Cohort -2B, 4 of 7 for Dose Exploration: Cohort -3, and 15 of 25 for Dose Expansion: Cohort -1. These are descriptive participant counts within the named cohorts.

The serious-event terms listed are abdominal pain (42.9%), diarrhoea (28.6%), colitis (28.6%), vomiting (20.0%), small intestinal obstruction (14.3%), and enteritis (14.3%). The registry information does not identify a denominator for these term percentages. The terms may overlap within participants, so the percentages are not additive and should not be treated as mutually exclusive categories.

These summaries should not be confused with the primary DLT endpoint. DLTs had a specific treatment-relatedness definition and a limited safety evaluation period; serious adverse event summaries are a separate safety description. The registry does not report event-level detail or comparative safety estimates, and the cohort counts do not support a causal comparison.

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

The record describes a phase 2, open-label, single-group study of nal-IRI with 5-FU/LV and oxaliplatin in previously untreated metastatic pancreatic adenocarcinoma. It documents dose exploration and dose expansion and provides descriptive serious adverse event counts for the listed cohorts. This information can help readers understand the structure of the study and the kind of safety experience recorded.

The record does not report the numerical result for its primary endpoint, the number of participants with DLTs in Part 1A. It also does not report numerical results for the listed secondary outcomes, which include response and time-to-event measures. Accordingly, it cannot support a quantified conclusion about DLT frequency, response, progression-free survival, overall survival, or duration of response. It also cannot show how precisely any such outcome was estimated.

The study title refers to a comparison with nab-paclitaxel plus gemcitabine, but the registry states that this comparative part was removed before it began. The posted Part 1 results therefore do not compare the nal-IRI regimen with that comparator. Cohort-to-cohort differences in the serious adverse event counts are not randomized treatment effects and should not be presented as proof of a safety advantage or disadvantage.

In general, a completed study can have results that are not displayed in a registry record. The absence of numerical outcomes from this record means those results are unavailable for interpretation from the registry information; it does not mean that outcomes were not measured or that no analysis was conducted. A fuller assessment would require the relevant outcome estimates, their denominators and uncertainty, and the analysis methods. No treatment recommendation follows from these descriptive registry data.

14. Why This Trial Matters Statistically

This study illustrates why the design actually analyzed matters as much as the study title. The title describes a comparison, but the registry record states that the comparative Part 2 was removed before initiation and that the clinical study report covers single-arm Part 1. Readers who rely on the title alone could mistake dose exploration and expansion cohorts for a controlled comparison.

The primary endpoint also shows the importance of distinguishing related but non-identical safety outcomes. A serious adverse event count is not the same measure as a protocol-defined DLT count. The DLT endpoint applied a treatment-relatedness criterion and a specified evaluation window. Without its result, the serious-event summaries cannot answer the primary endpoint question.

From a statistical perspective, this record is a useful reminder that counts need denominators, outcome definitions, and analysis populations to be interpretable. Even when cohort denominators are listed for serious events, the absence of a randomized comparator and uncertainty estimates limits between-cohort inference. For the primary endpoint, the missing numerical result prevents assessment even of the basic event frequency.

The registry lists several secondary outcomes, but their estimates are not reported in the registry record. That gap also prevents evaluation of precision and multiplicity. The study’s phase and enrollment do not fill in those missing results or reveal the statistical rationale. Clear separation of the planned study, the initiated study, the analyzed population, and the outcomes actually reported is essential for sound interpretation.

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 main trial-specific limitation is that the comparative Part 2 described in the title was removed before it began. The posted Part 1 evidence is single-group and non-comparative, so it cannot estimate a randomized contrast against nab-paclitaxel plus gemcitabine. The dose exploration and dose expansion cohorts should not be treated as arms of a controlled trial.

The primary outcome result is absent from the registry record. Although the DLT definition, timeframe, and safety population are described, the DLT count and its analysis denominator are not. The secondary outcome names are listed, but numerical estimates for those outcomes are not reported. This restricts interpretation to design details and the available descriptive serious adverse event summaries.

The serious-event information has limited detail. The registry provides counts by cohort and percentages for listed event terms, but does not report the denominator attached to those term percentages in the information available. Nor does the summary provide event timing, severity grades, duration, exposure, or participant-level overlap. The percentages for different terms may refer to overlapping participants and should not be combined.

The record does not report the statistical analysis plan, sample-size justification, missing-data procedures, multiplicity approach, interim analyses, or endpoint-specific analysis populations. These omissions make it difficult to assess how analyses were selected and how incomplete observations were handled. The registry enrollment of 56 should not be taken as the denominator for every outcome. These are limitations of the information reported in the registry record; they do not establish what analyses or additional reporting may exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma — NCT02551991.
• Registry record last updated 2022-10-10; status last verified 2022-10.
• Results first posted 2022-10-10.
• 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.

19. Record Summary

NCT02551991 is a completed, open-label phase 2 study sponsored by Ipsen, with registry enrollment of 56. Its analyzed results concern Part 1 dose exploration and dose expansion of nal-IRI with 5-FU/LV and oxaliplatin in previously untreated metastatic pancreatic adenocarcinoma. The comparative Part 2 against nab-paclitaxel plus gemcitabine was removed before initiation.

The primary endpoint was the number of participants with DLTs in Part 1A, assessed during a defined safety window. The registry describes the endpoint but does not report its numerical result. It lists secondary efficacy outcomes without numerical results. Cohort-level serious adverse event counts and selected event-term percentages are reported descriptively; they do not establish comparative effects. The registry record does not report the detailed analysis plan, missing-data methods, multiplicity procedures, or sample-size justification.