Standard treatment of metastatic colorectal cancers relies on fluoropyrimidines, irinotecan alone or in association with fluoropyrimidines, oxaliplatin in association with fluoropyrimidines, bevacizumab and anti EGFR antibodies. After failure of classical regimen the national reference frame on the basis of phase II study proposes an association of fluoropyrimidine and mitomycin. These treatments give response rates of 10-20% with progression free survivals from 2 to 3 months. Hepatic intra-arterial chemotherapy is logical in the case of isolated hepatic metastases nonaccessible to curative resection: 1) hepatic metastases are vascularized by hepatic arterial system in contrast to nontumoral hepatic parenchyma; 2) arterial perfusion of oxaliplatin leads to a strong extraction by the liver during the first passage, a high intra-tumoral concentration and a low systemic concentration. So oxaliplatin is a drug of choice for arterial treatment but combination with fluoropyrimidines is impossible because of need for prolonged perfusion. Floxuridin is not available in France. Raltitrexed, a definitive inhibitor of the thymidylate synthase, does not require a prolonged perfusion and could be a good substitute.In a previous pilot study we demonstrated the feasibility, safety and efficacy of combination of raltitrexed and oxaliplatin arterial perfusion. Now we propose a phase II randomized clinical trial to evaluate the efficacy of hepatic arterial infusion of raltitrexed and oxaliplatin association versus standard chemotherapy for patients with metastases of colorectal origin restricted to the liver after failure of conventional chemotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
31
130 mg/m²Every 21 days
3 mg/m² with a maximum of 6 mg every 21 days
Centre Georges François Leclerc
Dijon, France
progression-free survival
Time frame: for each patient after the 6 months of treatment
Estimate the parameters of tumor perfusion using arterial CT Scan data
Time frame: for each patient of experimental arm every 9 weeks after the six months of treatment or until progression
Estimate the rate of objective response according to the criteria of CHOI and RECIST
Time frame: for each patient every 9 weeks during the 6 months of treatment or until progression
Estimate the overall survival which will be compared with the median of overall survival in other studies published in the literature
Time frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
Estimate the rate of secondary resectable hepatic metastases
Time frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
Estimate the tolerance of the treatment (NCI-CTCAE version 4.0)
Time frame: For each patient every 21 days during the six months of treatment and for one year of follow up or until progression
Estimate the quality of life (QLQ C30) and the fatigue MFI20
Time frame: after all data completion after the end of all patient follow-up (december 2013-anticipated)
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