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

Phase 2

Completed

• Conditions: Colorectal Cancer With Non Resectable Hepatic Metastasis
• Interventions: Drug: HIA DEBIRI + systemic FOLFOX

• Registration Number: NCT01839877
• Lead Sponsor: Federation Francophone de Cancerologie Digestive

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-04-12
• Study First Submitted QC: 2013-04-24
• Study First Posted: 2013-04-25
• Study Start: 2013-05
• Primary Completion: 2017-12
• Study Completion: 2019-01
• Results First Submitted: 2022-08-19
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-05
• Last Update Submitted: 2024-07-05
• Results First Posted: 2024-10-07
• Last Update Posted: 2024-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HIA DEBIRI + systemic FOLFOX	HIA DEBIRI + systemic FOLFOX	Intra-arterial hepatic beads loaded with irinotecan with systemic FOLFOX

Primary Outcome Measures

Name	Time	Method
Progression-free Survival Rate at 9 Months	at 9 months after inclusion	The primary endpoint was to evaluate the rate of patients alive without progression at 9 months after the start of treatment. Events to be considered for the endpoint were: * Progression : defined as radiological progression according to RECIST V1.1 criteria, as assessed by the investigator.; * Death Patients who progressed or died (from any cause) within 9 months of starting treatment were considered as failure for the primary endpoint. The first event which occured will be taken into accoun

Secondary Outcome Measures

Name	Time	Method
Overall Survival	up to 4 years after patient's inclusion	It was defined as the time interval between the date of inclusion and the date of death (whatever the cause). Patients lost to follow-up or alive at the time of analysis were censored at the date of last news.

Trial Locations

Locations (9)

CHU - Hôpital François Mitterand; 🇫🇷 Dijon, France

Centre Léon Berard; 🇫🇷 Lyon, France

CHU de la TIMONE; 🇫🇷 Marseille, France

Hôpital Rangueil; 🇫🇷 Toulouse, France

CHU Charles Nicolle; 🇫🇷 Rouen, France

Institut Paoli Calmette; 🇫🇷 Marseille, France

Hôpital Prive Jean Mermoz; 🇫🇷 Lyon, France

Hopital Saint André; 🇫🇷 Bordeaux, France

Hôpital Europeen G Pompidou; 🇫🇷 Paris, France