colorectal cancer with hepatic metastasis MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Fédération Francophone de Cancérologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically proven colorectal adenocarcinoma with hepatic metastasis(es) - At least one measurable hepatic metastasis according to the criteria RECIST v1.1 - No other metastatic sites except lung nodules accepted if number = 3 and 3 months - PNN > 1500/mm3, platelets > 100 000/mm3, Hb > 9 g/dLq - Total bilirubin 60%, proteinuria from 24H 50 mL/min according to MDRD formula - Patient affiliated to a social security scheme - Patient information and signature of the informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 228
Exclusion criteria
Exclusion criteria: - Contraindications specific to the installation of a KTHIA: thrombosis of the hepatic artery, arterial vascular anatomy may compromise a secondary hepatic resection. - Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR - Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack - Hypertension not controlled by medical treatment (SBP> 140 mmHg and/or DBP> 90 mmHg with blood pressure taken according to the diagram of the HAS) - A history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding in the 6 months preceding the start of treatment - Progressive gastroduodenal ulcer, wound or fractured bone - Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment - Transplant patients, HIV positive or other immune deficiency syndromes - Any progressive pathology not balanced over the past 6 months: hepatic failure, renal failure, respiratory failure - Peripheral neuropathy > 1 (NCI CT v4.0) - Patient with interstitial pneumonitis or pulmonary fibrosis - History of chronic diarrhea or inflammatory disease of the intestine, colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment - History of malignant pathologies during the past 5 years except basocellular skin carcinoma or in situ cervical carcinoma, properly treated - Patient already included in another clinical trial with an experimental molecule - Any known specific contraindication or allergy to the treatments used in the study (cf RCP Appendix 7) - Partial or complete DPD deficiency (Uracilemia = 16 ng/ml) - QT/QTc range > 450 msec for men and > 470 msec for women - K+ < LNL, Mg2+ < LNL, Ca2+ < LNL - Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test - Persons deprived of liberty or under supervision - Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparison of radiological and/or clinical progression free survival between intra-arterial administration of oxaliplatin (arms A and C) and intravenous administration of oxaliplatin (arms B and D). Progression was assessed according to the criteria RECIST v1.1 and according to the investigator.;Secondary Objective: -Toxicities according to NCI-CTC v4.0 -Evaluation of the best response under treatment, and radiological progression-free survival after central review of the X-rays -Best response obtained under treatment according to the investigator -Overall survival (median) -Hepatic progression free survival (median) -Evaluation of quality of life (QLQ-C30) -Early tumor shrinkage (response > 20%) at 8 weeks -Depth of response -Secondary resection rate -Histological response in case of secondary resection -Evolution of tumoral marker (CEA) - Progression free survival under 'active' treatment - Subgroup analysis on patients being treated with intra-arterial oxaliplatin versus intravenous oxaliplatin with bichemotherapy and with trichemotherapy;Primary end point(s): Progression free survival (median);Timepoint(s) of evaluation of this end point: To evaluate the primary end point we need to have 318 events (progression or death) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - The adverse events will be graded according to NCI CTCAE v4.0 before each chemotherapy cycle. - The best response under treatment will be evaluated based on the response RECIST v1.1 according to the investigator to the different X-rays; it will be described by the levels in the different categories: complete or partial response, stability, progression or non-evaluable. - Overall survival: defined by the time between the date of treatment beginning and the date of death, whatever the cause; patients alive will be censured at the date of latest news. - Hepatic progression free survival: defined by the time between the date of treatment beginning and the date of first hepatic progression or death, whatever the cause; patients alive without progression will be censured at the date of latest news. - Early tumour shrinkage (difference > 20%) at 8 weeks: defined as the relative difference between the sum of the largest diameters of the RECIST target lesions at 8 weeks and this sum at inclusion (prior to C1 before randomization). - Depth of response: defined as the relative difference between the sum of the largest diameters of the RECIST target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the RECIST target lesions at inclusion. - Secondary resection rate: Rate of patients who were able to benefit from a resection of their tumor (primary and/or secondary) after treatment (by mentioning the character R0, R1 or R2) - Evaluation of the histological response, TRG (Rubbia-Brandt L et al. Annals Oncol 2007) in case of hepatic resection - Evolution of the marker during treatment - Quality of life - Progression free survival under 'active' treatment defined by the time between the date of treatment beginning and the date of first progression under treatment (excluding therapeutic break) or death, whatever the cause; patients alive without progression will be censured at th | — |
Countries
Belgium, France
Contacts
Public ContactMeriem GUARSSIFI Chef de projets
Fédération Francophone de Cancérologie Digestive
Outcome results
None listed