Prospective study in patients with cancer of the colon or rectum with liver metastasis, of the efficacy and toxicity of standard therapy (chemotherapy + targeted therapy) combined with immunotherapy and internal radiotherapy targeting the liver
- Conditions
- MICROSATELLITE STABLE (MSS) COLORECTAL CANCER WITH LIVER-DOMINANT METASTASISTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002400-40-FR
- Lead Sponsor
- Fédération Francophone de Cancérologie Digestive
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 52
- 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 < 50 % of total liver volume
- No prior oncologic treatment for metastatic disease (i.e. chemotherapy, radiotherapy or investigational drug). Patients may have received adjuvant chemotherapy or (neo) adjuvant radiochemotherapy to the pelvis (tumor of the rectum), but the last dose of chemotherapy/radiotherapy must be administered at least 6 months prior to entry into this study. Analgesic radiotherapy of metastasis is permitted except on hepatic lesions and must be completed at least 14 days before inclusion.
- WHO performance status = 1
- Estimated life expectancy = 3 months
- Adequate hematological function: with neutrophils = 1,500 /mm3, platelet count = 100,000/mm3, hemoglobin > 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
- 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 < 500 IU/mL (or 2500 copies/mL) at screening. Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be managed per treatment guidelines. Patients receiving antivirals at Screening should have been treated for > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method