Smart dosing: tailoring cancer drug levels could extend life for colorectal patients

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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). Exclusion Criteria: Less than 6 months from the end of any prior chemotherapy, radiotherapy or adjuvant surgery. * Patient with a known non-indication or contraindication to first-line chemotherapy based on bevacizumab. * Cardiovascular contraindication to the prescription of bevacizumab: heart failure, cardiovascular event within 6 months, NYHA ≥ 2 (New York Heart Association), poorly controlled arterial hypertension, history of hypertensive crisis or hypertensive encephalopathy; Grade 3/4 anterior venous thromboembolism (NCI-CTCAE) * Inadequate hematological, hepatic and renal function * Urine test strip for proteinuria ≥ 2+ unless proteinuria \< 1 g / 24 hours is demonstrated. * Current or recent (within 10 days of study enrollment) use of aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day). * Current or recent use (within 10 days before the first dose of bevacizumab) of oral or parenteral therapeutic anticoagulants or thrombolytic agents for therapeutic purposes. * Untreated CNS metastases or treatment of brain metastases, either by surgical or radiological techniques, must have been completed more than 4 weeks before the first study treatment. * Surgical procedure (including open biopsy, surgical resection, wound revision, or other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to study enrollment or anticipation of study need for major surgery during the study. * Serious non-healing wound, active ulcer or untreated bone fracture. * Other neoplasias (previous or current), except: * i/ carcinoma in situ of the cervix adequately treated, * ii/ basal cell or squamous cell carcinoma of the skin, * iii/ cancer in complete remission for more than 5 years. * Other illnesses, which, according to the doctor, are life-threatening to the patient and/or which are uncontrolled. * Primary tumor in place and symptomatic (occlusion, hemorrhage). * Pregnant or breastfeeding women. * Patients unable to give consent. * Patients under guardianship, curatorship or legal protection.