MICROSATELLITE STABLE (MSS) COLORECTAL CANCER WITH LIVER-DOMINANT METASTASIS
Conditions
Interventions
Trade Name: CAPÉCITABINE MYLAN
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: CAPECITABINE
Other descriptive name: CAPECITABINE
Concentration unit: mg/ml milligram(s)/millilitre
Conce
Sponsors
Fédération Francophone de Cancérologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age =18 years - Histologically proven mismatch repair proficient metastatic colorectal cancer (pMMR and/or MSS) - Liver-dominant disease with up to 6 extrahepatic lesions (only peritoneal lesions are not allowed) if asymptomatic and without organ dysfunction. - Measurable disease according to RECIST 1.1 - Patient with initially unresectable disease according to the local multidisciplinary team and eligible for radioembolization according to the radiologist's opinion - Tumor volume 9 g/dL (5,6 mmol/l) - Adequate hepatic function: hepatic transaminases (ASAT and ALAT) = 5 x UNL, total bilirubin = 2 x UNL, alkaline phosphatase = 5 x UNL - Adequate renal function: creatinine clearance = 50 ml/min according MDRD (Modification of Diet in Renal Disease) - Patient affiliated to a social security system Information provided to patient and signature of the informed consent form by patient and the investigator 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: - Active infection still requiring intravenous antibiotics on the first scheduled day of protocol treatment - Symptomatic or untreated central nervous system metastasis - Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for = 5 years, - Other malignancy in the 5 years prior to inclusion in the study, except for localized cancer in situ, basal or squamous cell skin cancer - Confirmed peritoneal carcinomatosis (lesions detectable on CT-scan and/or MRI) - Active autoimmune disease or inflammatory bowel disease - Bone marrow allograft or solid organ transplant history - History of idiopathic pulmonary fibrosis, drug-induced pneumonitis or evidence of active pneumonitis on screening chest CT-scan - Positive tests for HIV or other immunodeficiency syndromes - Active hepatitis B or hepatitis C. 1 - If patient has HBV, meets the following criteria as applicable to the infection type to be eligible: for patients with inactive/asymptomatic carrier, chronic, or active HBV: HBV DNA 2 weeks prior to enrollment and should continue treatment on study. 2 - For patients with HCV : to be eligible, patients with detectable HCV RNA should remain on continuous, effective antiviral therapy during the study. - Active tuberculosis - No contraindication to angiography and selective hepatic catheterization such as bleeding diathesis or coagulopathy with serious bleeding risk that is not correctable by usual therapy of hemostatic agents. Patients on anticoagulant therapy may be included but must be on low-molecular-weight heparin (excluding VKA and NOACs) and must be stopped 24 hours before invasive procedures according to usual recommendations (SIRT) - Significant presence of ascites, cirrhosis, portal hypertension, main portal venous tumor involvement or thrombosis on clinical or radiological evaluation Previous radiotherapy in the upper abdominal region (liver or liver vessels in the radiation field) - If primary tumor is non-resected, it must be asymptomatic - Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if they receive a dose equivalent to no more than 10 mg of prednisone equivalent dose per day, and corticosteroid administration is permitted by a route resulting in minimal systemic exposure (cutaneous, rectal, articular, ocular or inhalation) is authorized) - Partial or complete DPD deficiency - Known hypersensitivity to any components of bevacizumab, Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies and any other contraindications to the use of investigational medicinal products - Allergy to contrast agents that do not allow radioembolization to be performed - Uncontrolled hypertension (blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg) - Clinically significant cardiovascular disease, for example cerebrovascular accidents = 6 months prior to the start of study treatment, myocardial infarction = 6 months prior to the start of study treatment, unstable angina, congestive heart failure of NYHA (New York Heart Association Funct
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the progression-free survival at 9 months (according to RECIST 1.1) according to the investigator.;Secondary Objective: - safety (NCI-CTCAE v 4.0) - median progression-free survival (RECIST 1.1 and immune-RECIST (iRECIST)) - liver specific progression-free survival (RECIST 1.1 and iRECIST) - extra-hepatic progression-free survival (RECIST 1.1 and iRECIST) - overall survival - overall best response rate (RECIST 1.1 and iRECIST) - response rates at weeks 9, 18 and 27 (hepatic and non-hepatic target lesions) - early tumor shrinkage - depth of tumor response - secondary resection rate - time to treatment strategy failure - biomarker analyses (ancillary studies);Primary end point(s): Progression-free survival at 9 months: percentage of patients alive and without a radiological progression (whatever the type of radiological progression: hepatic or extra-hepatic) 9 months after inclusion (using RECIST v1.1 criteria) according to the investigator;Timepoint(s) of evaluation of this end point: 12 months after last inclusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety: adverse events will be graded according to the NCI-CTCAE v 4.0 criteria before each cycle. - Median progression-free survival: progression-free survival (PFS) will be defined as the time between inclusion date and the first radiological progression (whatever the type of radiological progression: hepatic or extra-hepatic, according to RECIST 1.1 and iRECIST criteria) or death (whatever occurs first). Patients alive and without progression will be censored at date of last news. - Liver specific progression-free survival: PFS will be defined as the time between inclusion date and the first radiological hepatic progression (according to RECIST 1.1 criteria) or death (whatever occurs first). Patients alive and without hepatic progression will be censored at date of last news. - Extra-hepatic progression-free survival: PFS will be defined as the time between inclusion date and the first radiological extra-hepatic progression (according to RECIST 1.1 criteria) or death (whatever occurs first). Patients alive and without extra-hepatic progression will be censored at date of last news. - Overall survival: overall survival will be defined as the time between inclusion date and death (any cause). Patients alive will be censored at date of last news. - Overall best response rate: best response according to RECIST v1.1 and iRECIST will be evaluated regarding CT-scans done during the treatment period. - Response rates at weeks 9, 18 and 27: response (partial or complete responses) according to RECIST v1.1 and iRECIST for hepatic and non-hepatic target lesions. - Early tumor shrinkage: early tumor shrinkage will be defined as a response >20% (according to RECIST v1.1 and iRECIST) at week 9. - Depth of tumor response: depth of tumor response will be defined as the percentage of tumor shrinkage observed at the lowest point (nadir according to RECIST v1.1 and iRECIST). - Time to treatment strategy failure: is defined as the time between in | — |
Countries
France
Contacts
Public ContactGEILLON Flore
Fédération Francophone de Cancérologie Digestive
Outcome results
None listed