De-escalation Chemotherapies Versus Escalation in Non Pre-treated Unresectable Patients With Metastatic Colorectal Cancer (HIGH-LIGHT)

This is an interventional treatment trial for Colorectal Neoplasms focused on measuring colorectal, cancer, metastasis Read More

Inclusion Criteria:

• Metastatic colorectal cancer, histologically proven (on primary tumour and/or metastases)
• Unresectable and non-pretreated metastases
• BRAF wild-type
• Patient considered able to receive 3 lines of chemotherapy
• At least one measurable target lesion > 1 cm according to RECIST 1.1 (Appendix 4)
• Tumour assessment according to RECIST, performed 4 weeks or less prior to randomization
• Age ≥ 18 years
• WHO performance status ≤ 2 (Appendix 5)
• No major surgery within 4 weeks prior to randomisation. Wound healing must be complete
• Life expectancy greater than 3 months
• Laboratory tests: Neutrophils ≥ 1500/mm3, platelets ≥ 100,000/mm3, haemoglobin > 9 g/dL
• Creatinine clearance > 30 mL /min (capecitabine dose modification if the creatinine clearance < 30-50 mL/min), serum creatinine < 1.25 x ULN
• Liver function tests: bilirubin < 1.25 x ULN, AST/ALT < 5 x ULN
• Women of childbearing age and men (who have sexual relations with women of childbearing age) must agree to use effective contraception without interruption throughout the duration of treatment and for 6 months after the last administration
• Signed informed consent

Exclusion Criteria:

• Patient with a potentially resectable colorectal cancer; i.e. for whom the goal of chemotherapy would be to make all metastases resectable
• Patients with symptomatic metastases
• Patient with aggressive disease and a large tumour volume
• Active gastroduodenal ulcer, wound or bone fracture
• At least one of the following laboratory values: Neutrophils <1500/mm3, platelets < 100,000/mm3, haemoglobin < 9 g/dL, total bilirubin > 1.5 N, alkaline phosphatase > 2.5 N (or > 5 N in case of hepatic involvement), serum creatinine > 1.5 N, 24 hr proteinuria > 1 g
• Chronic inflammatory bowel disease, extensive resection of the small bowel
• Clinically significant coronary artery disease or a history of myocardial infraction within the last 6 months. Uncontrolled hypertension while receiving chronic medication
• Abdominal or major extra-abdominal surgical procedure (except diagnostic biopsy) or radiation within 4 weeks before starting treatment
• Previous treatment with an anti-angiogenic or irinotecan
• Known or suspected central nervous system metastasis CNS metastases, or suspected CNS metastases
• Other previous malignancies within 5 years, except for basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix - Peritoneal macro-nodular carcinomatosis
• History of haemoptysis ≥ grade 2 (defined as ≥ 2.5 mL of bright red blood per episode) in the month prior to inclusion
• Known hypersensitivity to any component of bevacizumab or to one of the study treatments
• Active infection requiring intravenous antibiotics at start of treatment
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to treatment start
• Pregnant or breastfeeding women
• Concomitant participation in another clinical study involving a drug during the treatment phase and 30 days before starting the study treatment
• Patient unable to undergo medical treatment for geographical, social, psychological or legal reasons.