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
| Feature | FIRE-6 |
|---|---|
| NCT ID | NCT05217069 |
| Acronym | FIRE-6 |
| Title | FOLFIRI + Cetuximab + Avelumab RAS Wild-type CRC |
| Status | Completed |
| Start date | 2019-09-27 |
| Primary completion date | 2023-09-01 |
| Sponsor | Ludwig-Maximilians - University of Munich |
| Design | Single group, open label |
2. Clinical Question
Population
Patients with RAS wild-type colorectal cancer receiving the study treatment regimen.
Intervention
5-FU, folinic acid, irinotecan, cetuximab, and avelumab.
Comparator
No comparator arm was specified because the study used a single-group design.
Primary Question
The trial evaluated progression free survival rate after 8 months according to RECIST 1.1.
3. Trial Design
NA
None
Treatment
1
The study evaluates outcomes within one treatment strategy rather than comparing randomized groups.
4. Treatment Regimen
| Component | Intervention |
|---|---|
| Fluoropyrimidine | 5-FU |
| Folate component | Folinic Acid |
| Chemotherapy | Irinotecan |
| EGFR-directed therapy | Cetuximab |
| Maintenance therapy | Avelumab |
5. Endpoints
| Endpoint | Definition | Time Frame |
|---|---|---|
| Progression free survival (PFS) | The primary clinical objective is to determine the efficacy of a standard 1st-line regimen (FOLFIRI plus cetuximab) in patients with RAS wild-type mCRC with Avelumab maintenance in terms of progression free survival rate after 8 months according to RECIST 1.1. | up to 8 months |
6. Planned Analysis
The ClinicalTrials.gov record identifies progression free survival as the primary endpoint. No posted statistical analyses or efficacy estimates are available in the registry record.
For a progression-free survival endpoint, analysis typically involves time-to-event methods that account for patients who have not experienced progression or death at the time of analysis. Common approaches include Kaplan-Meier estimation of the progression-free survival function and summary measures of the event distribution.
The endpoint is designed to evaluate disease-control duration over the specified follow-up period. Because the registry does not report results, the observed progression-free survival rate and associated statistical estimates are not available.
7. Statistical Methodology
Progression-free survival analysis
PFS is a time-to-event endpoint. The event is generally defined by disease progression or death, while patients without an event at the analysis cutoff contribute follow-up information through censoring.
RECIST 1.1 assessment
The registry specifies that progression-free survival is assessed according to RECIST 1.1. This framework provides standardized criteria for evaluating tumor response and progression.
Single-group trial interpretation
Because FIRE-6 uses a single-group design, the statistical interpretation differs from randomized comparative trials. Observed outcomes describe the treated population but do not provide a randomized estimate of treatment effect versus an external comparator.
8. Statistical Methods Explained
Why is progression-free survival analyzed as a time-to-event endpoint?
PFS incorporates both the timing of disease progression and the possibility that some patients have not yet experienced progression at the analysis date. This avoids requiring all patients to have identical follow-up durations.
What does RECIST 1.1 contribute to the analysis?
RECIST 1.1 provides standardized criteria for determining radiographic response and progression, helping make endpoint assessment more consistent.
Why does a single-group design affect interpretation?
Without a randomized comparator, differences between treated patients and other populations may reflect patient characteristics, disease factors, or other differences rather than treatment alone.
Why is censoring important in PFS?
Patients may remain progression-free when follow-up ends. Statistical methods must account for these incomplete observations rather than treating them as failures or excluding them.
9. Limitations
- No randomized comparator: The single-group design does not estimate a randomized treatment difference.
- No posted statistical analyses: The registry does not provide formal statistical analysis results.
- Endpoint uncertainty: Without reported outcomes, the distribution of progression-free survival cannot be evaluated.
- Generalizability: Applicability depends on how closely future populations resemble the enrolled study population.
10. Why This Trial Matters Statistically
FIRE-6 illustrates several important principles in clinical trial statistics, including the interpretation of phase 2 single-group studies, the analysis of progression-free survival, and the role of standardized response criteria.
| Concept | How it appears in FIRE-6 |
|---|---|
| Phase 2 methodology | Evaluation of a treatment strategy before larger confirmatory development. |
| Time-to-event analysis | Progression-free survival measured over time. |
| Censoring | Patients without observed progression contribute partial follow-up information. |
| RECIST 1.1 | Standardized assessment framework for progression. |
| Single-group interpretation | Outcomes describe the treated cohort rather than a randomized comparison. |
11. Sources
- ClinicalTrials.gov record: NCT05217069