Bevacizumab-based Chemotherapy Tailored to the Pharmacokinetics of Bevacizumab in First-line Treatment of Unresectable Metastatic Colorectal Cancer: a Randomized, Multicenter, Double-blind Phase 3 Study
Bevacizumab is a standard drug for metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy. However, inter-individual pharmacokinetic variability was observed for bevacizumab and an exposure-response relationship for efficacy was described for bevacizumab in mCRC patients treated with 1st-line bevacizumab-based chemotherapy.
• Patients aged ≥18 years.
• Histologically proven metastatic colorectal adenocarcinoma (on primary tumor and/or metastases) inoperable, well documented, i.e. not compatible with complete oncological resection at inclusion.
• For whom treatment with bevacizumab is indicated.
• For women of childbearing age: effective contraception.
• ECOG Performance status (PS) 0-2.
• No prior treatment of metastatic disease (in the case of adjuvant treatment, interval between the end of chemotherapy and relapse \> 6 months if fluoropyrimidine alone or \> 12 months if FOLFOX).
• At least one evaluable or measurable lesion assessed by computed tomography (CT) according to RECIST v1.1 criteria.
• Life expectancy greater than 3 months.
• Adequate hematological, renal and hepatic biological parameters: neutrophils ≥ 1.5x109/L; platelets ≥ 100x109/L; hemoglobin ≥ 9 g/dL; serum creatinine \<150 μmol/L; bilirubinemia ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase \< 5xULN; proteinuria \< 2+ (urine dipstick) or ≤ 1 g/24h.
• Written informed consent signed by the patient.
• Patient affiliated to a French social security system.
⁃ Randomization criteria in the experimental phase:
⁃ \- Serum concentration of bevacizumab on D14 ≤ 15.5 mg/L (measured just before the 2nd infusion of bevacizumab).