Valproic Acid in Combination With Bevacizumab and Oxaliplatin/Fluoropyrimidine Regimens in Patients With Ras-mutated Metastatic Colorectal Cancer

Inclusion criteria * Age \>=18 years * Histologically confirmed diagnosis of colorectal adenocarcinoma * Stage IV of disease (according to TNM 8th edition) * RAS mutations * Clinical or radiologic evidence of disease (at least one target or non target lesion according to RECIST 1.1) * ECOG performance status 0 to 1 * Life expectancy \> 3 months * Use of an acceptable mean of contraception for men and women of childbearing potential * Adequate recovery from previous surgery. At least 28 days should elapse from a surgical procedure or from performing a biopsy for the enrolment into the study * Written informed consent Exclusion criteria Cancer related * RAS wild type colorectal cancer Prior, current or planned treatment related * Prior chemotherapy or any other medical treatment for advanced colorectal cancer (previous adjuvant chemotherapy is allowed if ended \> 6 months before relapse or \> 24 months if the adjuvant treatment included oxaliplatin) * Radiotherapy to any site for any reason within 28 days prior to randomization (palliative radiotherapy to bone lesions is allowed if \>=14 days before randomization) * Patient who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor like activity, such as valproic acid * Full dose anticoagulation with warfarin * Current or recent (within the last 10 days) use of aspirin (\>325 mg/day) or chronic use of other full dose nonsteroidal antiinflammatory drugs (NSAIDs) with antip…