TAS-102 and Yttrium-90 Microsphere Radioembolization in Treating Patients with Metastatic Colorectal Cancer That Cannot Be Removed by Surgery

Inclusion Criteria

• Of any ethnic or racial group
• Diagnosis of unresectable metastatic colorectal adenocarcinoma with liver-dominant bilobar disease; diagnosis may be made by histo- or cyto-pathology, or by clinical and imaging criteria as is standard of care at University of California, San Francisco (UCSF)
• Disease progression or intolerance to at least two prior Food and Drug Administration (FDA)-approved therapeutic regimens
• If extrahepatic disease is present, it must be asymptomatic
• If a primary tumor is in place, it must be asymptomatic
• Measurable target tumors using standard imaging techniques (RECIST version [v.] 1.1 criteria)
• Tumor replacement =< 50% of total liver volume
• Current Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 through screening to first treatment on study
• Completion of prior systemic therapy at least 14 days prior to enrollment
• Able to understand informed consent

Exclusion Criteria

• At risk for hepatic or renal failure * Serum creatinine > 1.5 mg/dl * Serum bilirubin > 1.3 mg/ml * Albumin < 2.0 g/dL * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper normal limit * Any history of hepatic encephalopathy * Cirrhosis or portal hypertension * Clinically evident ascites (trace ascites on imaging is acceptable)
• Contraindications to angiography and selective visceral catheterization * Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device) * Severe allergy or intolerance to contrast agents, narcotics, or sedatives that cannot be managed medically
• Symptomatic lung disease
• Prior therapy with TAS-102
• Contraindications to TAS-102 * Absolute neutrophil count < 1,500/ul * Platelet count < 75,000/ul * Allergy or intolerance to TAS-102
• Unresolved toxicity of greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 2 due to prior therapies
• Evidence of potential delivery of * Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration; or * Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments
• Evidence of any detectable technetium Tc-99m albumin aggregated (Tc99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop such flow
• Previous radiation therapy to the lungs and/or to the upper abdomen
• Any prior arterial liver-directed therapy, including transarterial chemoembolization (TACE), arterial embolization (TAE), and 90Y radioembolization
• Any intervention for, or compromise of the ampulla of Vater
• Active uncontrolled infection; presence of latent or medication-controlled human immunodeficiency virus (HIV) and/or viral hepatitis is allowed
• Significant extrahepatic disease * Symptomatic extrahepatic disease (including primary tumor, if unresected) * Greater than 10 pulmonary nodules (each =< 20 mm in diameter) or combined diameter of all pulmonary nodules > 15 cm * Peritoneal carcinomatosis
• Life expectancy less than 3 months
• Pregnant or lactating female
• In the investigator’s judgment, any comorbid disease or condition that would place the patient at undue risk and preclude safe use of radioembolization or TAS-102