Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies (NCT02109445), a randomized phase 2 study. The primary outcome is Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1.

2. Clinical Question

The study was designed around two related questions in people with previously untreated metastatic pancreatic ductal adenocarcinoma. The Phase 1b portion was intended to assess the safety of PF-03084014 combined with gemcitabine and nab-paclitaxel and determine a maximum tolerated dose. The Phase 2 portion was intended to evaluate the triple combination’s efficacy in terms of overall survival. The registered primary outcome, however, is the number of participants with dose-limiting toxicities in Cycle 1. No DLT count or overall-survival comparison is reported in the registry record.

The study is listed as randomized and unmasked, but the record does not describe the allocation method or the number assigned to each treatment group. Its brief summary describes a planned Phase 1b safety and dose-finding portion followed by a Phase 2 overall-survival evaluation. The available registered primary outcome instead focuses on first-cycle toxicity. These are distinct questions: a DLT count can describe early tolerability, while an overall-survival comparison would address a longer-term efficacy outcome. Neither question can be answered fully from the posted results because the DLT result and comparative survival analysis are not reported in the registry record.

3. Trial Design

The registry describes a randomized study with no masking and identifies its phase as Phase 2. The official title and brief summary describe a Phase 1/2 study, with a Phase 1b portion intended to evaluate dose and safety before a Phase 2 portion evaluating overall survival. The record lists three treatment descriptions: PF-03084014 with gemcitabine and nab-paclitaxel in Phase 1; the same combination in Phase 2 Arm A; and gemcitabine plus nab-paclitaxel in Phase 2 Arm B. The record does not report the dose levels, randomization procedure, allocation ratio, or participant counts by arm.

Enrollment was 3. The study started on 2014-09-03, had a primary completion date of 2014-11-06, and is listed as terminated. The reason for termination is not reported in the registry record, so the status and dates alone do not establish why recruitment or study conduct ended. The registry record does not explain how the planned Phase 1 and Phase 2 portions related to one another in practice, or whether the Phase 2 comparison proceeded as intended.

The registered primary outcome is the number of participants with DLTs during Cycle 1, defined as 28 days. Its evaluable population includes enrolled participants who received study treatment and either experienced a DLT during the first cycle or completed the one-cycle observation period. Only 2 of the 3 participants were evaluable for DLTs. The registry record does not report the DLT count among those evaluable participants. It lists 30 outcome measures and no posted analyses. Consequently, the record documents the study’s planned comparison and endpoint but does not provide the outcome estimates needed to assess the primary question or compare the Phase 2 arms.

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: All enrolled participants who received study treatment and who either experienced DLT during the first cycle, or completed the 1-cycle observation period, were considered evaluable for DLT. Only 2 of the 3 participants were evaluable for DLTs.

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 Participants With Dose-limiting Toxicities (DLTs) in Cycle 1, measured over Cycle 1 (28 days).

The primary endpoint counts participants with a dose-limiting toxicity during Cycle 1, a 28-day period. A DLT was defined as a Grade 3 or 4 clinically relevant non-hematologic and/or hematologic toxicity considered at least possibly related to study medication, or a delay of more than 2 weeks in receiving the next scheduled cycle because of persisting treatment-related toxicities. The endpoint therefore combines specified toxicities with a treatment delay attributed to persisting toxicity.

In general, a first-cycle DLT endpoint is used in early treatment evaluation because it focuses on serious treatment-related problems that arise during an initial observation period. Counting participants rather than counting all events gives a participant-level summary: the count concerns how many people met the DLT definition, not the total number of separate toxicities. The endpoint is relevant to a dose-finding objective because early toxicity information can inform assessment of tolerability at a dose level. It does not, by itself, measure tumor response or survival.

The registry record says that 2 of the 3 enrolled participants were evaluable for DLTs, but it does not report how many of those evaluable participants experienced a DLT. It also does not report the dose levels or a maximum tolerated dose result. Thus, the endpoint definition and analysis population are described, while the observed endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is primarily descriptive. It states the intended design, defines the primary endpoint, identifies the DLT-evaluable population, and gives participant counts for adverse events. It does not report an inferential analysis of the primary endpoint or a comparison of the Phase 2 treatment groups. The record lists no posted analyses. As a result, there is no reported test statistic, confidence interval, or estimate of treatment effect to interpret.

What a participant count represents

The registered primary endpoint is a count of participants meeting a binary definition: a participant either experienced a qualifying DLT during the observation period or did not. For a binary endpoint, a count is often read alongside the number of participants assessed. The registry gives the number evaluable, but it does not give the number with DLTs. Without both pieces, the observed event proportion cannot be described from the registry record. No proportion should be inferred from the evaluable count alone.

Participant-level counting differs from event-level counting. A participant can experience more than one adverse event, while a count of participants affected records whether a person had one or more events within the reported category. These are not interchangeable summaries. The serious adverse event figures report affected participants in the treatment group; the listed terms are also reported with percentages. The record does not provide enough detail to infer how many separate occurrences of each event were recorded.

What a confidence interval would add

In general, a confidence interval describes the range of estimates compatible with the observed data under a specified statistical method. It communicates precision as well as the central estimate. With very few participants, an estimate can be sensitive to the outcome of an individual participant, and its uncertainty can be substantial. This is general statistical context; the registry record does not report a confidence interval for the DLT count or a treatment comparison. Without a reported estimate and interval, precision cannot be assessed directly for the trial’s primary outcome.

Why randomization is not enough to interpret a comparison

Random allocation can support a fair comparison by limiting systematic differences between treatment groups in expectation. It does not itself supply a treatment-effect estimate, ensure that the groups were balanced in a small study, or replace reporting of the actual assigned group sizes and outcomes. Here, the record identifies the study as randomized and describes the Phase 2 regimens, but does not report allocation details, group sizes, comparative outcomes, or an analysis. Thus, the registry description establishes the intended design feature, not a demonstrated comparison.

The record is also unmasked. In general, masking can reduce the influence of knowledge of treatment assignment on some aspects of trial conduct and outcome assessment. The impact depends on the endpoint and procedures. The registry record does not describe outcome-assessment procedures or explain how the absence of masking was handled. No conclusion about bias can be made from that design label alone.

Over-dispersion and count outcomes

Over-dispersion is a general issue for count data when variability exceeds what a chosen probability model expects. It matters because a model that understates variability can produce uncertainty estimates that are too narrow. The primary endpoint is described as a participant count with an event, rather than a recurrent-event count, and the registry record does not report a fitted model or an over-dispersion assessment. The concept is relevant to statistical modeling in general but cannot be used to characterize an analysis that is not reported.

Planning calculations and observed evidence

Sample-size calculations are planning illustrations, not observed power. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustration is based on a fraction of an observed effect. Such assumptions do not establish the trial’s actual design rationale, and the record does not report a sample-size justification for this study. A planning calculation cannot substitute for an observed result or demonstrate that the study had a particular probability of detecting an effect. In particular, it should not be read as evidence that the Phase 2 comparison was adequately powered.

The intended Phase 2 overall-survival outcome would ordinarily require methods suited to time-to-event data, with clear definitions of the analysis population, follow-up, censoring, and treatment comparison. These are general considerations. The registry record does not report the survival analysis method, survival estimates, event counts, censoring details, or an analysis plan. Therefore, there is no basis to assess how such an analysis was performed or how precise its results might be.

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("PF-03084014 + Nab-Paclitaxel + Gemcitabine")
n      <- c(2)
events <- c(2)
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  PF-03084014 + Nab-Paclitaxel + Gemcitabine  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 30 outcome measures, including the primary DLT endpoint and secondary safety, laboratory, vital-sign, QTc, and pharmacokinetic outcomes. When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase if each is tested separately. In general, a prespecified multiplicity strategy can address that concern, but the choice depends on the study’s objectives and analysis plan. A multiplicity adjustment or testing hierarchy is not reported in the registry record.

The record gives no posted analyses and does not report result values for the primary DLT outcome or the planned Phase 2 overall-survival comparison. It also does not report whether analyses were prespecified, whether any interim analyses were conducted, or how any such analyses would have been handled. Those details should not be inferred from the listed outcomes or from the terminated status.

Missing-data handling is not reported in the registry record. The DLT description does identify the evaluable population: participants who received study treatment and either experienced a DLT during the first cycle or completed the one-cycle observation period. Only 2 of the 3 enrolled participants were evaluable. The reason the remaining participant was not evaluable, and the treatment of that participant in any other analysis, are not reported in the registry record. Rules for incomplete follow-up, withdrawal, censoring, and missing outcome measurements are also not reported.

The record does not specify whether an intention-to-treat population, a treated population, or other analysis populations were used for outcomes beyond the DLT evaluability description. Nor does it provide sensitivity analyses to show how alternative missing-data assumptions might affect results. With no reported outcome estimates or analysis details, the effect of multiplicity and missingness cannot be quantified for this study.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: vomiting (33.3%), alanine aminotransferase increased (33.3%), aspartate aminotransferase increased (33.3%), pulmonary embolism (33.3%).

For the PF-03084014, nab-paclitaxel, and gemcitabine group, the registry reports 3 participants at risk for serious adverse events and 2 participants affected. For other adverse events, it reports 3 participants at risk and 3 affected. These are participant counts, not a measure of event severity beyond the distinction between serious and other adverse events, and they do not indicate how many separate events each participant experienced.

The listed serious adverse event terms are vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, and pulmonary embolism. Each term is reported at 33.3%. The registry record does not provide corresponding comparative figures for the gemcitabine-plus-nab-paclitaxel arm. It also does not report deaths in the adverse-event summary. The absence of a reported death count should not be interpreted as evidence that no deaths occurred.

These safety figures describe a small group and do not provide a controlled estimate of differences between regimens. The record does not report timing, duration, recurrence, or participant-level overlap among the listed terms. The DLT result is also not reported, and adverse-event counts should not be treated as a substitute for that endpoint.

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

The registry record documents a randomized, unmasked study with a planned Phase 1b dose and safety component and a planned Phase 2 overall-survival evaluation. It records 3 participants enrolled, identifies the treatment regimens, and defines the primary DLT endpoint. It also reports that 2 participants were evaluable for DLTs and gives adverse-event participant counts for the triple-combination group.

Those descriptions do not establish the observed DLT frequency. The number of evaluable participants with a DLT is not reported in the registry record. Nor does the record report a maximum tolerated dose, the Phase 2 overall-survival results, or a comparative estimate between the triple combination and gemcitabine plus nab-paclitaxel. The design alone cannot show whether one regimen differed from the other on efficacy or safety.

The adverse-event figures indicate that the registry recorded serious adverse events affecting 2 of 3 participants in the triple-combination group and other adverse events affecting 3 of 3. The listed serious terms are reported at 33.3% each. These figures do not establish how the regimens compare, and the record does not report deaths. No treatment recommendation or conclusion about clinical benefit follows from these descriptive data.

More generally, results from a small number of participants are typically imprecise, and the registry record contains no confidence intervals with which to evaluate precision. This general point is especially relevant when the planned objective includes a treatment comparison, but it does not supply a trial-specific uncertainty estimate. The termination status also does not explain why the study ended. The record supports a description of what was planned and what limited safety information was posted; it does not support an efficacy conclusion or a complete assessment of the intended study questions.

14. Why This Trial Matters Statistically

This study illustrates the difference between a trial design and a trial result. The registry describes randomization, treatment groups, an early DLT endpoint, and a planned Phase 2 overall-survival question. Yet it reports enrollment of 3, only 2 DLT-evaluable participants, and no posted analyses. The design description is useful for understanding the questions investigators intended to address, but it is not evidence that those questions were answered.

It also highlights why analysis populations and endpoint results need to be reported together. The DLT definition is detailed, and the registry specifies who counted as evaluable. Without the number of evaluable participants who met the endpoint, readers cannot assess the observed outcome. Similarly, an adverse-event count in one treatment group cannot serve as a comparative safety analysis when corresponding group results and allocation counts are not reported.

From a statistical perspective, the small enrollment makes uncertainty central. In general, estimates based on few participants can be strongly affected by individual outcomes. Confidence intervals and clear reporting of group sizes would help readers understand precision, while an explicit analysis plan would clarify how multiple outcomes and incomplete data were handled. Those elements are not reported in the registry record.

The record therefore matters as an example of the limits of interpreting a trial from design labels and partial outcome information. A randomized designation, a planned efficacy endpoint, and a safety summary each answer different descriptive questions. None replaces a reported estimate with its uncertainty. The record offers a limited account of study conduct and posted safety counts, while leaving the primary DLT result and planned comparative efficacy question unresolved.

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 is that the registry record does not report a result for the primary DLT endpoint. Although 2 of the 3 participants were evaluable, the number who experienced a DLT is missing. The stated maximum-tolerated-dose objective is also not accompanied by a reported dose level or dose-finding result.

Enrollment was 3, and the record does not report participant allocation by treatment arm. This prevents readers from determining how many participants contributed to either Phase 2 group or whether the planned comparison was carried out. The Phase 2 overall-survival outcome is described as an objective, but survival estimates and comparative analyses are not reported. The reason for termination is also not reported in the registry record.

The available safety summary is limited to the triple-combination group. The registry does not report comparable adverse-event counts for the gemcitabine-plus-nab-paclitaxel arm, nor does it describe event timing, duration, recurrence, or overlap. Deaths are not reported in the registry record; that omission does not establish that none occurred. The listed serious event terms and percentages therefore provide only a narrow descriptive view.

Other trial details needed to assess the evidence are not reported in the registry record, including doses, randomization procedures, the sample-size justification, statistical analysis methods, multiplicity handling, missing-data procedures, interim analyses, and the analysis populations beyond the DLT evaluability definition. These omissions constrain interpretation without implying a particular reason for the study’s status or the absence of results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies — NCT02109445.
• Registry record last updated 2019-01-10; status last verified 2018-12.
• Results first posted 2017-06-12.
• 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

The registry record describes a randomized, unmasked Phase 1/2 study of PF-03084014 with gemcitabine and nab-paclitaxel in previously untreated metastatic pancreatic ductal adenocarcinoma. Phase 2 Arm B is described as gemcitabine plus nab-paclitaxel. The study enrolled 3 participants, started on 2014-09-03, had a primary completion date of 2014-11-06, and is listed as terminated.

The registered primary endpoint is the number of participants with DLTs during Cycle 1, defined as 28 days. Only 2 of the 3 participants were evaluable for DLTs; the DLT count is not reported in the registry record. The registry describes overall survival as the intended Phase 2 efficacy outcome but does not report a comparative result. Safety counts are posted for the triple-combination group, without a corresponding comparative summary for the other regimen.