metastatic colorectal adenocarcinoma without a RAS mutation
Conditions
Interventions
Trade Name: Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou
perfusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN
Sponsors
Fédération Francophone de Cancérologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically proven colorectal adenocarcinoma without RAS mutation - Confirmed, non-resectable metastatic disease (Stage IV) - No prior chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months - At least one measurable metastasis according to the RECIST v1.1 criteria - Age = 18 years - WHO = 2 - Neutrophils = 1500 /mm3, platelets = 100 000/mm3, Hb = 9 g/dL - Creatinine clearance = 50 mL/min according to the MDRD formula - Serum bilirubin = 25 µmol/L, AST, ALT, Alk Phos = 2.5 x ULN or = 5 x ULN in case of liver metastases - PT = 60%, albumin = 25g/L - Estimated life expectancy = 3 months - Patient affiliated to a social security scheme - Patient informed and informed consent form signed 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: - Presence of uncontrolled symptomatic brain metastases - RAS mutation (KRAS or NRAS mutation) - Patient taking warfarin. If treated with anticoagulant at the indicated effective dose, this must be replaced with low molecular weight heparin before inclusion - Known DPD deficiency - Peripheral neuropathy = 1 (NCI CTCAE v4.0) - Patient with interstitial pneumonitis or pulmonary fibrosis - History of chronic diarrhoea or inflammatory disease of the colon or rectum, or obstruction or sub-obstruction non-resolved during symptomatic treatment - chronic skin disease not controlled - Treatment with sorivudine or its chemically related analogues such as brivudine - Association with the yellow fever vaccine - Patient included simultaneously in another therapeutic trial with an experimental molecule (example: chemotherapy, targeted therapy, immunotherapy) - Any known specific contraindication or allergy to the medicinal products used in the study - Patient simultaneously included in another clinical trial involving an investigational drug - Arterial hypertension not controlled by medical treatment (Systolic BP = 160 mmHg end/or diastolic BP = 90 mmHg) - Any progressive pathology not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure - The following conditions in the 6 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischaemic attack - Patient who has received a transplant, is seropositive for HIV, hepatitis B or hepatitis C or has other immunodeficiency syndromes - History of malignant pathologies during the past 5 years except basal cell carcinoma of the skin or cervical carcinoma in situ, properly treated - QT/QTc interval > 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 who have not had a pregnancy test. Women of childbearing potential should agree to use a method of contraception during treatment of the trial and at least 4 months after discontinuation of oxaliplatin therapy, at least 2 months after discontinuation of panitumumab therapy and at least 30 days after discontinuation of 5-fluorouracil or capecitabine. Men must agree to use a method of contraception during treatment and at least 6 months after stopping oxaliplatin therapy and at least 3 months after stopping 5-fluorouracil or capecitabine. - Persons in custody or under wardship - Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the disease control duration; Secondary Objective: - Progression-free survival (PFS) 1 (first radiological progression or death) - Successive periods of progression-free survival - The best tumour response during treatment, the early response rate at 6 weeks and the maximum depth of response, evaluated according to the RECIST V1.1 criteria according to the investigator and centralised imaging review - Overall survival - Quality of life of patients (EORTC QLQ-C30) - Time to final deterioration of the overall health score - Safety profile, particularly in regard to skin toxicity events (acneiform rash, xeroderma, paronychia) - The predictive value of early evolution (at two weeks) of the circulating tumour DNA level correlated with the RECIST 1.1 response rate and the PFS 1 - The appearance of resistance mutations and clonal selection through analysis of circulating tumour DNA every two months. ;Primary end point(s): the primary endpoint is the disease control duration;Timepoint(s) of evaluation of this end point: 2 years after last patient registration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival (PFS) 1 (first radiological progression or death) - Successive periods of progression-free survival - The best tumour response during treatment, the early response rate at 6 weeks and the maximum depth of response, evaluated according to the RECIST V1.1 criteria according to the investigator and centralised imaging review - Overall survival - Quality of life of patients (EORTC QLQ-C30) - Time to final deterioration of the overall health score - Safety profile, particularly in regard to skin toxicity events (acneiform rash, xeroderma, paronychia) - The predictive value of early evolution (at two weeks) of the circulating tumour DNA level correlated with the RECIST 1.1 response rate and the PFS 1 - The appearance of resistance mutations and clonal selection through analysis of circulating tumour DNA every two months. ;Timepoint(s) of evaluation of this end point: 2 years after last patient registration | — |
Countries
Belgium
Contacts
Public ContactClinical Trial Coordinator
Belgian Group of Digestive Oncology (BGDO)
Outcome results
None listed