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
Primary Purpose
Colorectal Cancer With Non Resectable Hepatic Metastasis
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
HIA DEBIRI + systemic FOLFOX
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer With Non Resectable Hepatic Metastasis focused on measuring Metastatic colorectal Cancer
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.
Sites / Locations
- Hopital Saint André
- CHU - Hôpital François Mitterand
- Hôpital Prive Jean Mermoz
- Centre Léon Berard
- Institut Paoli Calmette
- CHU de la TIMONE
- Hôpital Europeen G Pompidou
- CHU Charles Nicolle
- Hôpital Rangueil
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
HIA DEBIRI + systemic FOLFOX
Arm Description
Intra-arterial hepatic beads loaded with irinotecan with systemic FOLFOX
Outcomes
Primary Outcome Measures
Progression-free survival rate at 9 months
Secondary Outcome Measures
safety of the study treatment
Adverse event rate; all grade, grades 1-2 and grades 3-4
Overall survival
Full Information
NCT ID
NCT01839877
First Posted
April 12, 2013
Last Updated
December 21, 2020
Sponsor
Federation Francophone de Cancerologie Digestive
Collaborators
Biocompatibles UK Ltd
1. Study Identification
Unique Protocol Identification Number
NCT01839877
Brief 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
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
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
May 2013 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
January 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Federation Francophone de Cancerologie Digestive
Collaborators
Biocompatibles UK Ltd
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer With Non Resectable Hepatic Metastasis
Keywords
Metastatic colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
58 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIA DEBIRI + systemic FOLFOX
Arm Type
Experimental
Arm Description
Intra-arterial hepatic beads loaded with irinotecan with systemic FOLFOX
Intervention Type
Drug
Intervention Name(s)
HIA DEBIRI + systemic FOLFOX
Primary Outcome Measure Information:
Title
Progression-free survival rate at 9 months
Time Frame
at 9 months after inclusion
Secondary Outcome Measure Information:
Title
safety of the study treatment
Description
Adverse event rate; all grade, grades 1-2 and grades 3-4
Time Frame
at 9 months after inclusion
Title
Overall survival
Time Frame
2 years after last patient in
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien TAIEB, Pr
Organizational Affiliation
Fédération Francophone de Cancérologie Digestive
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Saint André
City
Bordeaux
ZIP/Postal Code
33075
Country
France
Facility Name
CHU - Hôpital François Mitterand
City
Dijon
Country
France
Facility Name
Hôpital Prive Jean Mermoz
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Centre Léon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Institut Paoli Calmette
City
Marseille
ZIP/Postal Code
13273
Country
France
Facility Name
CHU de la TIMONE
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Hôpital Europeen G Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU Charles Nicolle
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Hôpital Rangueil
City
Toulouse
ZIP/Postal Code
31059
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
32507854
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.
Results Reference
result
Learn more about this trial
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
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