Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Colorectal Cancer w/Liver Dominant Disease

Exclusion Criteria

• •Child-Pugh Class B or C cirrhosis or evidence of clinically significant portal hypertension by history, endoscopy, or radiologic studies (large abdominal varices, prior history of varices by endoscopy).
• •New York Heart Association functional classification II, III or IV or active cardiac condition(s), including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease that create(s) undue risks of undergoing general anesthesia.
• •History or evidence of clinically significant pulmonary disease that precludes the use of general anesthesia.
• •History of bleeding disorders, presence of brain metastases, or other intracranial abnormalities found on baseline radiologic imaging that would put them at risk for bleeding with anti-coagulation.
• •Known varices at risk of bleeding, including medium or large esophageal or gastric varices, active peptic ulcer, or history of recent hemoptysis.
• •Active second malignancy, or has history of recently definitively treated invasive cancer in the past 2 years prior to enrolment with the exception of non-melanoma skin cancer.
• •Peritoneal lesions or large abdominal masses.
• •Use of immunosuppressive drugs.
• •Inability to temporarily stop chronic anti-coagulation therapy.
• •Active bacterial infections with systemic manifestations.
• •Active viral infection, including Hepatitis B and Hepatitis C infection. NOTE: Patients with anti-hepatitis B core antibody (HBc) positive, or hepatitis B surface antigen (HBsAg) but DNA negative are allowed exception(s).
• •Severe allergic reaction to iodine contrast that cannot be controlled by premedication with antihistamines and steroids.
• •History of or known hypersensitivity to melphalan or the components of the melphalan/HDS system.
• •History of known hypersensitivity to heparin or the presence of heparin-induced thrombocytopenia.
• •Uncontrolled endocrine disorder including diabetes mellitus, hypothyroidism, or hyperthyroidism.
• •Received anti-cancer therapy including radiotherapy or investigational agent for any indication ≤ 30 days prior to randomization
• •Previous treatment with trifluridine-tipiracil.
• •History of allergic reactions attributed to compounds of similar composition to trifluridine/tipiracil or any of its excipients.
• •Hereditary problems of galactose intolerance, total lactase deficiency or glucosegalactose malabsorption.
• •History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients.
• •History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
• •Contraindications to bevacizumab, including uncontrolled hypertension, history of active fistula or bowel perforation (unless in the setting of a resected primary), history of CVA or arterial thrombotic event in the last 1 year, or history of venous thrombotic event in the last 30 days.
• •Evidence of hepatic vein or portal vein thrombosis
• •Prior chemoembolization or radioembolization to the liver or prior hepatic arterial infusion therapy