Intra-arterial Hepatic Beads Loaded With Irinotecan With Concomitant Chemotherapy With FOLFOX in Patients With Colorectal Cancer With Unresectable Liver Metastases: a Phase II Multicenter Study

Study Overview
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Brief Summary
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Treatment of patients with colorectal cancer having liver metastases is currently based on systemic chemotherapy. Triple therapy with 5FU, oxaliplatin and irinotecan intravenously was effective in terms of response and secondary resectability, however it is particularly toxic. Hepatic intra-arterial chemotherapy (HIA) has been the subject of several studies. It has shown good efficacy with oxaliplatin and FUDR. However, the procedure is difficult to set up and reserved for experienced centers. The objective of this protocol is to use a triple therapy based on 5FU and oxaliplatin associated to irinotecan which is administered by hepatic intra-arterial route, loaded onto microbeads (DEBIRI). Furthermore, the procedure for chemo-embolization DEBIRI is limited to 2 sessions, and therefore could be more easily generalized.

Official Title
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Intra-arterial Hepatic Beads Loaded With Irinotecan With Concomitant Chemotherapy With FOLFOX in Patients With Colorectal Cancer With Unresectable Liver Metastases: a Phase II Multicenter Study

Conditions
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Colorectal Cancer With Non Resectable Hepatic Metastasis

Intervention / Treatment
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* Drug: HIA DEBIRI + systemic FOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven colorectal adenocarcinoma, Liver metastases radiologically or histologically proven At least one measurable liver lesions by RECIST v1.1 Age ≥ 18 years WHO Index < or = 2 Life expectancy ≥ 3 months No extrahepatic disease except lung nodules if number < or = 3 and size < 10 mm each Healthy liver <60% Primary tumor resected or still in place No prior chemotherapy for metastases treatment (except a perioperative chemotherapy, if the last cycle was administered at least 12 months ago) Adjuvant chemotherapy after resection of the primary authorized if the last cycle was administered at least 12 months ago Normal hepatic function: total bilirubin ≤ 1.5 N; AST ≤ 5N; ALT ≤ 5N and PAL ≤ 5N TP ≥ 60% Adequate hematologic function: ANC ≥ 1500/mm3, platelets ≥ 100 000/mm3, Hb ≥ 9g/dl Good renal function: creatinine clearance ≥ 60 mL / min No cardiac dysfunction: no cardiovascular events in the last 6 months or no NYHA ≥ 2 Exclusion Criteria: Patient eligible for curative treatment (resection and / or radiofrequency ablation) by a multidisciplinary decision (including the opinion of a liver surgeon) Pregnant or lactating woman or patients of both sexes and of childbearing age not using adequate contraception History of cancer, except skin cancer (other than melanoma), carcinoma in situ of the cervix uteri treated curative. Other cancers treated with curative intent are permitted provided they did not relapse over the last 5 years Peripheral neuropathy Inflammatory Bowel Diseases Intestinal obstruction Chronic liver disease (viral, alcoholic or metabolic) Immune Deficiency Syndromes (history of transplantation, infection with HIV) Known to have contraindications to 5FU, oxaliplatin, folinic acid, irinotecan or to contrast products Patients with known contraindications against hepatic embolization procedures: Presence of biliary-digestive anastomosis or biliary stent Cruoric or tumor thrombosis of the portal vein Patient who for psychological, social, family or geographical reasons could not be followed up regularly Legal disability (persons deprived of liberty or under guardianship) Patient is not affiliated to a social security scheme Participation in another concurrent study investigating the effect of treatment and this until 4 weeks after the end of the concurrent study.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIA DEBIRI + systemic FOLFOX<br>Intra-arterial hepatic beads loaded with irinotecan with systemic FOLFOX | Drug: HIA DEBIRI + systemic FOLFOX<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate at 9 months |  | at 9 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of the study treatment | Adverse event rate; all grade, grades 1-2 and grades 3-4 | at 9 months after inclusion | 
| Overall survival |  | 2 years after last patient in | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal Cancer