Soluble Vascular Endothelial Growth Factor Receptor 2 as Predictor of Benefit From Bevacizumab Beyond Progression in Metastatic Colorectal Cancer (CIRCUS)

Inclusion Criteria:

• Male or female of ≥ 18 years of age
• Progressive disease during or after first-line chemotherapy plus bevacizumab, including fluoropyrimidine alone (5-fluorouracil or capecitabine), fluoropyrimidine in combination with oxaliplatin (XELOX or FOLFOX regimen) or irinotecan (FOLFIRI regimen) or with oxaliplatin and irinotecan (FOLFOXIRI regimen);
• No more than 3 months from the last administration of bevacizumab and evidence of progressive disease are allowed;
• Measurable disease according to RECIST 1.1.
• Indication to second-line treatment with a bevacizumab-containing second-line regimen (second-line XELOX, FOLFOX, FOLFIRI and FOLFOXIRI plus bevacizumab are allowed);
• Neutrophils 1.5 x 109/L, Platelets 100 x 109/L, Hgb >9 g/dl
• Total bilirubin 1.5 time the upper-normal limits (UNL) of the institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase 2.5 x UNL, 5 x UNL in case of liver metastases
• Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL
• Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24 hr
• Will and ability to comply with the protocol
• Written informed consent to study procedures.

Exclusion Criteria:

• Patient unable to give consent
• Absolute contraindications to the use of bevacizumab.