REVOLUTION - Randomized phasE 2 study of Valproic acid in combination with bevacizumab and Oxaliplatin/fLUoropyrimidine regimens in patients with ras-mutated metastaTIc cOlorectal caNcer

Lab values

• Tumors without RAS mutations • Prior chemotherapy or any other medical treatment for advanced mCRC (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) • Any other invasive malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA) • 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 • Known dihydropyrimidine dehydrogenase (DPD) deficiency • Pregnancy or nursing • Concomitant pathologies or laboratory alterations or concomitant medications use that prevent or contraindicate the use of study drugs • Brain metastases

• Age = 18 • 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 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