Colorectal Neoplasms, Liver Neoplasms
Conditions
Brief summary
To see if Disease Free Survival (DFS) is improved when complete surgical resection of liver metastases (R0) is followed by chemotherapy with CPT-11 and 5-FU/FA as FOLFIRI regimen, compared to 5-FU/FA alone.
Interventions
DRUGIrinotecan + 5 FU + folinic acid
irinotecan 180 mg/m2 folinic acid 400 mg/m2 (DL) followed by 5 FU bolus 400 mg/m2 5 FU continuous infusion (2400 mg/m2 over 46 hours) every 2 weeks
DRUGFolinic Acid + 5 FU
folinic acid 400 mg/m2(DL) followed by bolus 5 FU 400mg/m2 5 FU continuous infusion (2400 mg/m2 over 46 hours) every 2 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Histologically proven adenocarcinoma of the colon or rectum with complete resection of primary tumour. * Complete surgical resection (R0) of the liver metastasis(es) within a minimum of 3 weeks, and a maximum of 8 weeks prior to the first study treatment infusion. * Exclusively hepatic metastasis (es) : absence of bone, lung and brain metastases.
Exclusion criteria
* Prior hepatic radiation or resection. * Prior radiofrequency ablation or cryoablation Incomplete surgical resection of liver metastasis (es). * Prior chemotherapy for metastatic disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | last tumor assessment date or cut-off date, whichever is earlier. | time interval between the date of randomization and the earliest date of local, regional or distant relapse, or death due to cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rates | Median follow-up time (42 months) | Probability of being alive was calculated in a yearly increment. |
Countries
Belgium, Denmark, France, Germany, Hong Kong, Israel, Italy, Portugal, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Ukraine, United Kingdom
Participant flow
Recruitment details
study was conducted at 66 centers.
Pre-assignment details
Eligible subjects (subjects who underwent complete liver metastasis resection within 8 weeks of study drug administration) were randomly assigned. Of the 321 subjects randomized in the study, all but 15 were treated.
Participants by arm
| Arm | Count |
|---|---|
| 5-FU/FA simplified 5-FU/FA De Gramont regimen for a period of twelve 2-week cycles (6 months) | 153 |
| Irinotecan + 5-FU/FA irinotecan plus simplified 5-FU/FA De Gramont regimen for a period of twelve 2-week cycles (6 months) | 153 |
| Total | 306 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 8 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Randomized Not Treated | 7 | 8 |
| Overall Study | Relapse | 15 | 7 |
| Overall Study | specified by site | 4 | 9 |
| Overall Study | Withdrawal by Subject | 3 | 12 |
Baseline characteristics
| Characteristic | 5-FU/FA | Irinotecan + 5-FU/FA | Total |
|---|---|---|---|
| Age Continuous | 61 years | 63 years | 62 years |
| Sex: Female, Male Female | 53 Participants | 63 Participants | 116.0 Participants |
| Sex: Female, Male Male | 100 Participants | 90 Participants | 190.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 146 / 152 | 150 / 154 |
| serious Total, serious adverse events | 15 / 152 | 32 / 154 |
Outcome results
Primary
Disease Free Survival (DFS)
time interval between the date of randomization and the earliest date of local, regional or distant relapse, or death due to cancer.
Time frame: last tumor assessment date or cut-off date, whichever is earlier.
Population: Full analysis set = all treated subjects according to randomization: n=153, 153 for 5-FU/FA \& Irinotecan + 5-FU/FA, respectively. Safety analysis set (for Adverse Events) = all treated subjects according to treatment actually received (1 subject randomized to 5-FU/FA actually received treatment from Irinotecan + 5-FU/FA). n=152, 154 as above).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 5-FU/FA | Disease Free Survival (DFS) | 21.6 months |
| Irinotecan + 5-FU/FA | Disease Free Survival (DFS) | 24.7 months |
95% CI: [0.67, 1.2]
p-value: 0.468Log Rank
Secondary
Overall Survival Rates
Probability of being alive was calculated in a yearly increment.
Time frame: Median follow-up time (42 months)
Population: Full analysis set = all treated subjects according to randomization: n=153, 153 for 5-FU/FA \& Irinotecan + 5-FU/FA, respectively. Safety analysis set (for Adverse Events) = all treated subjects according to treatment actually received (1 subject randomized to 5-FU/FA actually received treatment from Irinotecan + 5-FU/FA). n=152, 154 as above).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5-FU/FA | Overall Survival Rates | 24 months | 0.845 survival rate |
| 5-FU/FA | Overall Survival Rates | 12 months | 0.961 survival rate |
| 5-FU/FA | Overall Survival Rates | 36 months | 0.716 survival rate |
| Irinotecan + 5-FU/FA | Overall Survival Rates | 12 months | 0.973 survival rate |
| Irinotecan + 5-FU/FA | Overall Survival Rates | 24 months | 0.881 survival rate |
| Irinotecan + 5-FU/FA | Overall Survival Rates | 36 months | 0.727 survival rate |