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Rectal Cancer Phase 3 Randomized Trial NCT01804790

PRODIGE 23: Complete Statistical Analysis of Neoadjuvant mFolfirinox in Resectable Locally Advanced Rectal Cancer

An independent statistical review of the PRODIGE 23 phase 3 randomized trial evaluating neoadjuvant mFolfirinox-based treatment strategies in patients with resectable locally advanced rectal cancer.

ClinicalTrials.gov record: NCT01804790

This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.

1. Trial at a Glance

PRODIGE 23 was a phase 3 randomized parallel-group treatment trial evaluating neoadjuvant mFolfirinox in patients with resectable locally advanced rectal cancer.

461
Enrollment
3
Phase
2
Arms
3 years
Primary endpoint timeframe
FeatureDescription
ConditionCancer of the Rectum
AllocationRandomized
Design modelParallel
MaskingNone
Primary purposeTreatment
Lead sponsorUNICANCER

2. Clinical Question

Population

Patients with resectable locally advanced rectal cancer.

Intervention

mFolfirinox with additional trial-specified treatment components including radiotherapy, capecitabine, and TME surgery.

Comparator

The control treatment pathway included mFolfox6 or capecitabine.

Primary question

Does the investigational strategy improve 3-year disease-free survival compared with the control arm?

3. Trial Design

01
Randomization
461 patients
02
Parallel arms
2 groups
03
Treatment
Protocol therapy
04
Surgery
TME
05
Assessment
Disease-free survival

Investigational strategy

  • mFolfirinox
  • Radiotherapy 50 Gy
  • Capecitabine
  • TME surgery

Control strategy

  • mFolfox6 or capecitabine
  • Radiotherapy 50 Gy
  • TME surgery

4. Endpoints

EndpointDefinitionTime frame
Disease-free survivalTo compare the 3-year disease-free survival between the investigational arm and the control arm.3 years

5. Planned Analysis

The ClinicalTrials.gov record identifies disease-free survival as the primary endpoint. Disease-free survival is a time-to-event endpoint generally evaluated using methods such as Kaplan-Meier estimation, comparison of survival curves, and regression approaches that estimate relative treatment effects.

No formal statistical analyses were posted to ClinicalTrials.gov. The registry reports the endpoint definition and timeframe but does not provide posted estimates, confidence intervals, or p-values for the primary endpoint.

6. Statistical Methodology

Time-to-event analysis

Disease-free survival measures the time until a defined disease-related event or censoring. Statistical methods for this endpoint account for patients who have different follow-up durations.

Conceptual survival function

S(t) represents the probability that an individual remains event-free beyond time t.

Randomization

The randomized allocation creates the framework for comparing treatment strategies while reducing the influence of measured and unmeasured baseline differences between groups.

7. Statistical Methods Explained

Why is disease-free survival used as the primary endpoint?

Disease-free survival combines information about recurrence-related events and follow-up time. It can provide an earlier assessment of treatment effects than overall survival in some cancer trials.

Why does randomization matter?

Randomization allows treatment groups to be compared according to their assigned intervention rather than according to characteristics that may influence outcomes.

How is a time-to-event endpoint analyzed?

Patients are followed over time, and observations without the event by the end of follow-up contribute information through censoring methods.

Why are confidence intervals important?

A confidence interval describes uncertainty around an estimated treatment effect. It does not describe the range of outcomes experienced by individual patients.

Why can a registry endpoint description not replace a statistical analysis?

An endpoint definition explains what will be measured, but interpretation requires the reported estimates, uncertainty measures, and statistical testing results.

8. Limitations

9. Why This Trial Matters Statistically

PRODIGE 23 is an example of a randomized phase 3 oncology trial where the statistical framework centers on a time-to-event endpoint. The design illustrates how randomized comparisons, endpoint definitions, and survival-analysis methods work together in evaluating treatment strategies.

ConceptApplication
RandomizationParallel randomized comparison
Primary endpoint3-year disease-free survival
Time-to-event methodsAppropriate framework for disease-free survival analysis
InterpretationRequires both effect estimates and uncertainty measures

10. Sources