Clinical trial NCT01839877: 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
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer With Non Resectable Hepatic Metastasis
Keywords: Metastatic colorectal Cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
Collaborators: name: Biocompatibles UK Ltd
First posted: 2013-04-25
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival Rate at 9 Months
timeFrame: at 9 months after inclusion
Secondary outcomes:
measure: Overall Survival
timeFrame: up to 4 years after patient's inclusion
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hopital Saint André
city: Dijon
country: France
facility: CHU - Hôpital François Mitterand
city: Lyon
country: France
facility: Hôpital Prive Jean Mermoz
city: Lyon
country: France
facility: Centre Léon Berard
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Marseille
country: France
facility: CHU de la TIMONE
city: Paris
country: France
facility: Hôpital Europeen G Pompidou
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Toulouse
country: France
facility: Hôpital Rangueil
Study officials:
affiliation: Fédération Francophone de Cancérologie Digestive
name: Julien TAIEB, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pernot S, Pellerin O, Artru P, Monterymard C, Smith D, Raoul JL, De La Fouchardiere C, Dahan L, Guimbaud R, Sefrioui D, Jouve JL, Lepage C, Tougeron D, Taieb J; for FFCD1201-DEBIRI investigators/Collaborators. Intra-arterial hepatic beads loaded with irinotecan (DEBIRI) with mFOLFOX6 in unresectable liver metastases from colorectal cancer: a Phase 2 study. Br J Cancer. 2020 Aug;123(4):518-524. doi: 10.1038/s41416-020-0917-4. Epub 2020 Jun 8.