Intensified Chemotherapy in CRC After Resection of Liver Metastases

Study Overview
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Brief Summary
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Randomized, open label, multicentre phase II trial followed by phase III comparing overall survival after having selected the best experimental arm.

Official Title
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Randomized Phase II Trial Followed by Phase III Trial With Molecular Biology Study, Comparing a Standard Bi-therapy vs 3 Arms of Intensified Chemotherapy in Patients With Unresectable or Not Optimally Resectable Colorectal Cancer Liver Metastases.

Conditions
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Colorectal Cancer, Liver Metastases, Chemotherapy

Intervention / Treatment
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* Drug: FOLFIRI
* Drug: FOLFOX-4
* Drug: FOLFIRI-HD
* Drug: FOLFOX-7
* Drug: FOLFIRINOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven adenocarcinoma of the colon or rectum without previous resection, or clinically asymptomatic (with or without stent) Hepatic unresectable metastases R0: due to close vascular contact, or due to liver remaining mass less than 25 to 30 % of functional liver. Not optimally resectable metastases Extra-hepatic disease will be accepted in case of: asymptomatic primary tumour or tumor requiring no urgent surgery (in less than 3 months); three of less than three lung metastases (thoracic scan diameter less than 2 cm) and potentially respectable. Synchronous and metachronous hepatic metastases WHO performance status 0-1 Adjuvant chemotherapy allowed, except oxaliplatin and irinotecan based combination. No prior treatment of the liver metastases, whatever. Life expectancy equal or more than 3 months Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>FOLFIRI | Drug: FOLFIRI<br>* FOLFIRI : Irinotecan : 180 mg/m² 90 min continuous perfusion during levorin d1 every 2 weeks<br>|
| Active Comparator: B<br>FOLFOX-4 | Drug: FOLFOX-4<br>* FOLFOX 4 : Oxaliplatine : 85 mg/m² 2h continuous perfusion during levorin d1 every 2weeks<br>|
| Experimental: C<br>FOLFIRI-HD | Drug: FOLFIRI-HD<br>* High Dose FOLFIRI : Irinotecan : 260 mg/m² in 90min continuous perfusion during levorin d1 every 2 weeks<br>|
| Experimental: D<br>FOLFOX-7 | Drug: FOLFOX-7<br>* FOLFOX 7 : Oxaliplatine : 130 mg/m² in 2h continuous perfusion during levorin d1 every 2 weeks<br>|
| Experimental: E<br>FOLFIRINOX | Drug: FOLFIRINOX<br>* FOLFIRINOX : Oxaliplatine : 85 mg/m² 2h continuous perfusion followed by 1H rest followed by 90 min continuous perfusion of irinotecan : 180 mg/m² during levorin d1 every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | end of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | during study treatment | 
| Survival |  | 2 years | 
| Secondary resection |  | surgery after chemotherapy |