Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer (NCT01523457), a non-randomized phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

3. Trial Design

This was a completed Phase II study with a non-randomized, parallel design and no masking. Yale University is listed as the sponsor. The registry record gives enrollment as 75 and identifies metastatic pancreatic cancer and pancreatic cancer as conditions under study. The study dates recorded are a start in 2011-10 and primary completion in 2014-12.

The study evaluated modified FOLFIRINOX in two disease-defined groups: patients with metastatic pancreatic cancer and patients with locally advanced unresectable pancreatic cancer. The arms are described separately as MPC modified FOLFIRINOX and LAPC modified FOLFIRINOX. The intervention was not compared with a randomized alternative. Disease status defines the groups, so differences between their outcomes could reflect differences in the populations as well as other factors; the design does not isolate a treatment contrast between those groups.

The registry describes the modified regimen as administered every 2 weeks. Its arm descriptions include oxaliplatin, folinic acid, and irinotecan doses and infusion details, but the available descriptions end before all regimen information is complete. The brief summary identifies the regimen as a dose-attenuated modification of folinic acid, fluorouracil, irinotecan, and oxaliplatin. Further details about treatment delivery are not reported in the registry record.

The primary objective was progression-free survival in both disease groups. Secondary outcomes included objective response rate according to RECIST, overall survival, toxicity, resection rate in the locally advanced group, and associations between early changes in glucose metabolism on FDG-PET scanning and time to progression, response, and overall survival. The registry lists six outcome measures, but it does not report a statistical analysis plan or the numerical primary outcome result. The record also does not describe a randomized allocation process, masking, or a like-for-like control comparison; allocation is explicitly non-randomized and masking is absent.

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: Two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment (one due to cholecystitis with abscess and one due to cerebrovascular accident).

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: 75 patients, including 44 with MPC and 31 with LAPC, were enrolled. The demographics and disease characteristics of the 37 evaluable patients in the MPC cohort in this study are presented here. Seven of 44 patients with MPC were excluded from efficacy analysis due to voluntary withdrawal.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival, measured over 24 weeks.

Progression-free survival (PFS) concerns the length of time during which a patient remains alive without disease progression. As a general statistical concept, PFS combines information about disease control and survival, rather than measuring tumour shrinkage alone. The registry record expresses this primary endpoint as a percentage of participants at 24 weeks, making the focus a status at a stated assessment time rather than a reported median time-to-event estimate.

The endpoint is relevant to a study of advanced cancer because it describes whether progression has occurred by a defined point in follow-up. A fixed-time percentage can be easier to interpret as a proportion of participants meeting an endpoint at that point. Its interpretation depends on how progression and deaths are handled, how follow-up is managed, and which participants are included in the analysis. The registry description states that tumour response was assessed according to RECIST 1.1 by independent radiology review; the full PFS event definition and estimation details are not reported in the registry record.

The record gives 24 weeks as the timeframe but does not provide the observed PFS percentage for either disease group, a confidence interval, or other uncertainty measure. It also does not report the denominators used for the primary endpoint results. Therefore, the endpoint's intended meaning can be described, but its observed magnitude and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is expressed as a percentage of participants with an event or status of interest at 24 weeks. In general, a percentage summarizes the share of an analysis group meeting a defined outcome. To interpret it, readers need both the numerator and denominator, along with a clear endpoint definition and information about how missing assessments and follow-up are handled. The registry record names PFS and its timeframe, but does not report the observed percentages, analysis denominators, or uncertainty estimates.

What does a confidence interval add?

General explanation: a confidence interval expresses the statistical uncertainty around an estimated quantity under the analysis method used. A narrow interval indicates greater precision than a wide interval, while an interval alone does not resolve bias from study design or missing data. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the PFS estimate cannot be judged from this information.

Why does the design matter?

General explanation: random allocation can help balance measured and unmeasured participant characteristics across treatment groups, supporting a causal comparison under appropriate conditions. This study was non-randomized and had no masking. Its parallel arms correspond to different disease groups, MPC and LAPC. They therefore do not form randomized treatment and control groups. Comparisons between their results would be descriptive and could be influenced by differences between the populations, disease settings, or other factors not described in the record.

Independent radiology review using RECIST 1.1 is specified for tumour response. General explanation: a predefined response framework can make assessments more consistent, and independent review can reduce the influence of treatment-team expectations on image assessment. The registry does not provide further details about review procedures, adjudication, or how progression events were incorporated into the PFS analysis. Those details are not reported in the registry record.

How should event counts be read?

The adverse-event summary gives counts of affected participants and the number at risk for serious and other events, separately by arm. These figures describe the recorded event categories and denominators. They do not, by themselves, show event timing, recurrent events, severity gradations, treatment attribution, or duration. General explanation: a count of participants affected is different from a count of total events, because an individual may experience more than one event. The registry record does not give event-level detail sufficient to determine whether the displayed counts represent all events or to characterize recurrence.

The registry's sample-size assumptions describe planning illustrations based on an observed effect, rather than the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event outcomes, the planning illustrations use a total number of events, while other outcomes use participants per arm. These calculations are planning illustrations, not observed power and not evidence that the trial was prospectively designed around those assumptions. The registry record does not report the trial's own sample-size justification or statistical plan.

General explanation: power is a design property tied to a specified effect, variability, analysis method, and sample-size plan. A retrospective planning calculation based on an observed effect cannot establish the probability that the completed study would detect a true effect. It is sensitive to the observed estimate, which may itself be imprecise. The assumptions listed for the planning illustration should therefore be read as hypothetical inputs, not as a description of the original protocol.

What is over-dispersion, and is it addressed?

General explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. It can make standard errors too small if the model does not account for the extra variability. Whether over-dispersion is relevant depends on the outcome and analysis model. The registry record does not describe a model for the primary endpoint, a variance adjustment, or a method for addressing over-dispersion, so whether it was considered is not reported in the registry record.

The study has several registered secondary outcomes, including response, overall survival, toxicity, resection, and PET-related correlations. General explanation: when many outcomes or comparisons are examined, the chance of finding an apparently notable result by chance can increase. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address particular multiplicity concerns. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or inferential analyses. No adjustment method should be assumed.

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("MPC Modified FOLFIRINOX", "LAPC Modified FOLFIRINOX")
n      <- c(37, 29)
events <- c(20, 28)
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  MPC Modified FOLFIRINOX  37  20  54.1  36.9  70.5  38.4  69.0  38.3  69.0
ARM  LAPC Modified FOLFIRINOX  29  28  96.6  82.2  99.9  82.8  99.4  82.8  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and lists secondary outcome topics: objective response rate, overall survival, toxicity, resection rate for locally advanced disease, and correlations involving PET changes and clinical outcomes. It does not report a statistical analysis plan, a testing hierarchy, or a multiplicity adjustment. Thus, it is not possible to determine from the registry record whether any formal approach was used to control the chance of false-positive findings across secondary outcomes.

The registry states that two of 31 patients with LAPC were excluded from efficacy analysis because they did not complete four cycles to reach the first efficacy assessment. The reasons recorded are cholecystitis with abscess and cerebrovascular accident. The record does not specify the analysis population for the MPC arm, how missing assessments were treated, or whether any sensitivity analysis was performed. These details are not reported in the registry record.

General explanation: excluding participants without an assessment can affect the interpretation of an outcome if their outcomes differ systematically from those who remain in the analysis. The direction and magnitude of any such effect depend on the missingness and outcome patterns, which cannot be inferred from the exclusion statement alone. A reader would need the relevant analysis denominators, missing-data handling, and sensitivity analyses to evaluate this issue.

The recorded exclusion is an efficacy-population detail, not evidence by itself of a biased result. Since the endpoint estimate, denominators, and analytic methods are absent, the extent to which exclusions or other missing data affect the reported PFS result cannot be assessed. These analysis-population and missing-data details are not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry separates serious events from other adverse events and reports participants at risk and affected participants for each arm. In MPC, 0 serious events are listed among 44 at risk; in LAPC, 0 serious events are listed among 31 at risk. For other events, the registry reports 20 affected among 43 at risk in MPC and 11 affected among 31 at risk in LAPC. These are the recorded counts; no percentages or comparisons are calculated.

The serious-event summary lists no serious adverse-event terms. It also records 0 deaths in each arm. These entries describe what is present in the registry summary, not proof that no serious harms occurred outside the captured reporting or observation process. The registry record does not describe the adverse-event collection window, event definitions, severity categories for other events, treatment attribution, or whether participants could contribute multiple events.

General explanation: “participants affected” counts people with at least one event in the specified category, whereas total event counts can include repeated events in the same person. The summary should therefore be read as participant-level counts where that is what the record reports, not as a complete event-by-event toxicity profile. The available safety information does not support a randomized safety comparison, because the arms are non-randomized and correspond to different disease groups.

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

This registry record documents a completed Phase II study of modified FOLFIRINOX in metastatic and locally advanced unresectable pancreatic cancer. It identifies PFS at 24 weeks as the primary endpoint and describes secondary outcome topics. It also records an efficacy exclusion in the LAPC group and selected serious and other adverse-event counts. These registry entries describe the study and its registered outcomes, but they do not provide the numerical primary result.

Without the PFS percentages, denominators, confidence intervals, or analysis details, the primary endpoint's magnitude and precision cannot be evaluated. The record does not establish how often participants were progression-free at 24 weeks, nor whether an estimate was similar or different across the disease groups. The lack of a numerical result in the registry record is not evidence that the outcome was favorable or unfavorable; it means the result cannot be assessed from this record.

The non-randomized design also limits interpretation of comparisons between the MPC and LAPC arms. The groups are defined by different disease settings, and there is no like-for-like randomized control group. Any difference in outcomes between them could reflect population or disease differences rather than a treatment effect. The study record therefore does not support a causal comparison between those arms.

The safety counts provide a limited descriptive view. They show the serious and other event counts recorded for the specified denominators, but do not convey detailed event types, timing, recurrence, severity, or attribution. Likewise, registered secondary outcome names do not substitute for outcome estimates. Overall, the record can inform readers about the study question, design, selected analysis-population information, and the scope of safety reporting; it cannot establish the size, precision, or comparative effect of the treatment from the information recorded.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the distinction between a clearly stated research question and an interpretable outcome estimate. The registry specifies PFS as the primary objective, gives the 24-week timeframe, and identifies independent RECIST 1.1 review for tumour response. Those details help define what the study set out to assess. However, the registry record does not report the primary endpoint result, its denominator, or an uncertainty interval. Without those elements, readers cannot evaluate the observed estimate or its precision.

The study also shows why design structure matters when reading results. Its non-randomized arms represent MPC and LAPC, not treatment alternatives assigned at random. Those arm labels might invite comparison, but the groups are not a like-for-like control comparison. Separating descriptive outcomes from causal treatment contrasts is essential when interpreting non-randomized clinical evidence.

The stated LAPC efficacy exclusions highlight the importance of analysis populations. The record explains why two of 31 patients did not reach the first efficacy assessment, but does not provide enough information to evaluate the impact of those exclusions on the endpoint estimate. Reporting participant flow, analysis denominators, and missing-data methods alongside outcome estimates helps readers judge how closely an analysis represents the enrolled population.

Finally, the adverse-event summary demonstrates the limits of aggregate counts. Counts and denominators provide a basic description, but detailed event information is needed to understand the safety profile. The registry's planning assumptions also illustrate that sample-size calculations based on an observed effect are planning illustrations, not observed power and not necessarily the original design rationale. Together, these features make the record useful for understanding study structure while emphasizing what outcome reporting is needed for statistical 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 limitation for interpreting efficacy is that the registry record does not report the numerical primary PFS result at 24 weeks. It also does not give the endpoint denominators, uncertainty intervals, analysis method, or complete event definition. Consequently, the magnitude and precision of the primary result cannot be assessed from the record.

The non-randomized design has no randomized control arm, and the MPC and LAPC arms are different disease groups. Their outcomes should not be used as a direct treatment comparison. The record does not describe methods for adjusting for differences between participants or other potential sources of confounding.

For LAPC, two of 31 patients were excluded from efficacy analysis after not completing four cycles to reach the first assessment. The registry gives the reasons but does not state how the exclusion affected the endpoint estimate, whether other participants had missing data, or what sensitivity analyses were used. The corresponding analysis-population information for MPC is not reported in the registry record.

Safety reporting is limited to serious and other event counts and the listed denominators. The registry does not provide serious-event terms, detailed event descriptions, timing, severity, treatment attribution, or the adverse-event observation period. The recorded zero counts should therefore be interpreted as entries in this summary, not as a complete account of possible harms.

The record lists secondary outcomes but does not provide their results or a multiplicity plan. Further information on the original sample-size justification, statistical analysis plan, handling of missing data, and outcome analyses is not reported in the registry record. In addition, the available regimen descriptions are incomplete, limiting the treatment-delivery detail that can be assessed from this record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Modified FOLFIRINOX in Advanced Pancreatic Cancer — NCT01523457.
• Registry record last updated 2017-08-30; status last verified 2017-05.
• Results first posted 2017-08-30.
• 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 describes a completed Phase II study of modified FOLFIRINOX for metastatic pancreatic cancer and locally advanced unresectable pancreatic cancer. The study used non-randomized parallel arms without masking. The sponsor is Yale University, and the recorded enrollment is 75. The primary objective was PFS, expressed as a percentage of participants at 24 weeks, with tumour response assessed according to RECIST 1.1 by independent radiology review.

The record lists secondary outcomes involving response, overall survival, toxicity, resection, and PET-related correlations. It reports that two of 31 LAPC patients were excluded from efficacy analysis for not reaching the first efficacy assessment. The adverse-event summary gives serious and other event counts by arm. The numerical primary endpoint result, its precision, and the statistical analysis plan are not reported in the registry record.