Ignite Creation Date:
2024-05-05 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00126256
Status:
COMPLETED
Last Update Posted:
2015-08-13
First Post:
2005-08-02
Brief Title:
Trial Comparing Two Strategies of Chemotherapy for Metastatic Colorectal Cancer
Sponsor:
Gustave Roussy Cancer Campus Grand Paris
Organization:
Gustave Roussy Cancer Campus Grand Paris
Study Overview
Official Title:
Randomized Trial of Treatment Strategy for Chemotherapy in Colorectal Cancer FFCD 2000-05
Status:
COMPLETED
Status Verified Date:
2015-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The standard treatment of metastatic colorectal cancer is based on systemic chemotherapy Several effective drugs are currently available and can be administered either sequentially or in combination Most patients receive 2 or 3 lines of chemotherapy The aim of this randomized trial is to evaluate the potential benefit of a bitherapy with 5-fluorouracil 5-FU and oxaliplatin as first line chemotherapy compared with a sequential chemotherapy with 5-FU alone as first line chemotherapy followed by the combination of 5-FU with oxaliplatin in case of progressive disease in terms of progression-free survival and overall survival in patients with advanced colorectal cancer
Detailed Description:
Background
The addition of oxaliplatin and irinotecan to 5-FU improves tumor response rate and progression-free survival in patients with advanced colorectal cancer compared with 5-FU alone but increases toxicity It is not clear whether such combination therapies 5-FUoxaliplatin or 5-FUirinotecan should be systematically used as first line treatment or as second line treatment after 5-FU failure
Design open-label multicentric randomized trial
Aim The main objective of this multiline strategy trial was to compare two 5-FU based regimens with or without the addition of oxaliplatin to 5-FU in the first line setting in terms of progression-free survival after two lines of chemotherapy in patients with metastatic colorectal cancer
Treatment compared
Control arm first line 2-hour infusion 400 mgm² leucovorin LV followed by 5-fluorouracil 400 mgm² and 46-hours 2400 mgm² every 2 weeks LV5FU2 second line LV5FU2 oxaliplatin 100 mgm² as a 2-hour perfusion on day 1 FOLFOX6 third line LV5FU2 irinotecan 180 mgm² FOLFIRI
Experimental arm first line FOLFOX6 second line FOLFIRI third line 5-FU 250 mgm²day in continuous perfusion 7 out of 8 weeks or capecitabine 2500 mgm² per oral 14 out of 21 days or inclusion in a phase I
Inclusion criteria
Histologically confirmed metastatic colorectal adenocarcinoma
Unresectable metastasis
Bidimensionally measurable disease WHO criteria
WHO performance status of 2 or less
Adequate hematologic renal function and liver functions
No previous chemotherapy other than previous adjuvant chemotherapy or concomitant chemoradiotherapy with 5-fluorouracil and leucovorin for the treatment of the primary tumor completed at least 6 months before inclusion
Signed written inform consent
Quality of life questionnaire QLQ C-30 filled out
Exclusion criteria
Pregnant or breast-feeding women
No possible regular follow-up for psychological social or geographical reason
Severe cardiac respiratory renal or hepatic failure
Active coronary heart disease
Central nervous system metastases
Past history of second malignancies
Another investigational drug
Chronic inflammatory bowel disease
Previous chemotherapy with irinotecan or oxaliplatin based regimens
Randomization
Randomization is performed centrally using a minimization technique stratifying patients according to centre previous adjuvant treatment WHO performance status and number of metastatic sites
Outcomes
Progression-free survival after two lines of chemotherapy defined as the time duration from randomization until progression after two lines of chemotherapy or death whatever the cause in the absence of progression or last-follow-up
Overall survival secondary surgery response rate progression-free survival after the first and the third line of chemotherapy safety quality of life and costs
Follow-up
Tumor assessments is performed every 8 weeks quality of live assessment every 8 weeks until progression after 2 lines of chemotherapy or for one year if no progression After the end of the planned treatment patients are followed up until death or the cut-off date
Sample size and statistical analyses
570 patients 285 per arm will be needed to detect a difference in median of progression-free survival after two lines of chemotherapy of 3 months from 10 months in the control arm to 13 months in the experimental arm for a type I error of 5 and a power of 80 bilateral log rank test
The analysis will be performed according to the intent-to treat principle An interim analysis is planned after the inclusion of 400 patients with 3 months follow-up or the occurrence of 250 events and reviewed by an independent data monitoring committee
Estimated duration of the trial accrual period 3 years minimum follow-up one year
The addition of oxaliplatin and irinotecan to 5-FU improves tumor response rate and progression-free survival in patients with advanced colorectal cancer compared with 5-FU alone but increases toxicity It is not clear whether such combination therapies 5-FUoxaliplatin or 5-FUirinotecan should be systematically used as first line treatment or as second line treatment after 5-FU failure
Design open-label multicentric randomized trial
Aim The main objective of this multiline strategy trial was to compare two 5-FU based regimens with or without the addition of oxaliplatin to 5-FU in the first line setting in terms of progression-free survival after two lines of chemotherapy in patients with metastatic colorectal cancer
Treatment compared
Control arm first line 2-hour infusion 400 mgm² leucovorin LV followed by 5-fluorouracil 400 mgm² and 46-hours 2400 mgm² every 2 weeks LV5FU2 second line LV5FU2 oxaliplatin 100 mgm² as a 2-hour perfusion on day 1 FOLFOX6 third line LV5FU2 irinotecan 180 mgm² FOLFIRI
Experimental arm first line FOLFOX6 second line FOLFIRI third line 5-FU 250 mgm²day in continuous perfusion 7 out of 8 weeks or capecitabine 2500 mgm² per oral 14 out of 21 days or inclusion in a phase I
Inclusion criteria
Histologically confirmed metastatic colorectal adenocarcinoma
Unresectable metastasis
Bidimensionally measurable disease WHO criteria
WHO performance status of 2 or less
Adequate hematologic renal function and liver functions
No previous chemotherapy other than previous adjuvant chemotherapy or concomitant chemoradiotherapy with 5-fluorouracil and leucovorin for the treatment of the primary tumor completed at least 6 months before inclusion
Signed written inform consent
Quality of life questionnaire QLQ C-30 filled out
Exclusion criteria
Pregnant or breast-feeding women
No possible regular follow-up for psychological social or geographical reason
Severe cardiac respiratory renal or hepatic failure
Active coronary heart disease
Central nervous system metastases
Past history of second malignancies
Another investigational drug
Chronic inflammatory bowel disease
Previous chemotherapy with irinotecan or oxaliplatin based regimens
Randomization
Randomization is performed centrally using a minimization technique stratifying patients according to centre previous adjuvant treatment WHO performance status and number of metastatic sites
Outcomes
Progression-free survival after two lines of chemotherapy defined as the time duration from randomization until progression after two lines of chemotherapy or death whatever the cause in the absence of progression or last-follow-up
Overall survival secondary surgery response rate progression-free survival after the first and the third line of chemotherapy safety quality of life and costs
Follow-up
Tumor assessments is performed every 8 weeks quality of live assessment every 8 weeks until progression after 2 lines of chemotherapy or for one year if no progression After the end of the planned treatment patients are followed up until death or the cut-off date
Sample size and statistical analyses
570 patients 285 per arm will be needed to detect a difference in median of progression-free survival after two lines of chemotherapy of 3 months from 10 months in the control arm to 13 months in the experimental arm for a type I error of 5 and a power of 80 bilateral log rank test
The analysis will be performed according to the intent-to treat principle An interim analysis is planned after the inclusion of 400 patients with 3 months follow-up or the occurrence of 250 events and reviewed by an independent data monitoring committee
Estimated duration of the trial accrual period 3 years minimum follow-up one year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CET 815 | None | None | None |