The goal of this clinical trial is to help learn about the safety and feasibility of hepatic artery infusion chemotherapy for those who have colorectal liver metastases, both resectable and unresectable, or unresectable intrahepatic cholangiocarcinoma. The main questions it aims to answer are:

• safety and feasibility of installing a pump that deliveries chemotherapy to the hepatic artery (the blood vessel that supplies blood to the liver)
• help learn more about the safety of patients having pump refills at home or a local clinic versus having it routinely done at the hospital

Participants will have surgery to install a pump which is a standard surgical procedure. After surgery, participants will select to either receive treatment at the hospital facility or with a community oncologist that will provide cancer care to participants close to home, rather than in a large hospital or academic medical center.

The main treatment on study will last about 3-4 months.

Inclusion Criteria:

• Colorectal adenocarcinoma metastatic to the liver which is either Unresectable (group A) or Resectable (group B; ie, will be completely resected), AND with no definitive clinical or radiographic evidence of extrahepatic disease other than: metastatic disease to resectable peri-hepatic lymph nodes; up to 5 proven or suspected lung metastases, provided they are stable or responding in number and size for a minimum of 2-months of systemic chemotherapy and are amenable to SBRT or resection. or
• Histologically confirmed unresectable intrahepatic cholangiocarcinoma (group C), with presence of less than 70% liver involvement with no definitive clinical or radiographic evidence of extrahepatic metastatic disease other than resectable perihepatic lymph nodes.
• Patients > or equal 18 years of age
• ECOG Performance Status of 0 - 1 (APPENDIX C)
• Lab Values < or equal 14 days prior to study enrollment: absolute neutrophil count > or equal 1,500/mcL Total Bilirubin < or equal 1.5 mg/dL AST/ALT < 5 x institutional upper limit of normal (ULN) Platelets > or equal 100,000/mcL Creatinine < 1.5 mg/dL HGB > 8 g/dL INR < or equal 1.5
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Prior chemotherapy is acceptable if last dose given > or equal 3 weeks prior to study enrollment
• Any investigational agent is acceptable if last dose administered > or equal 3 months before study enrollment
• In order for patients to select treatment in the CO arm, they must have the ability to do telehealth visits, either via a home computer, tablet, or smartphone, either via home internet access or cellphone network.

Exclusion Criteria:

• Presence of distant non-liver metastatic disease confirmed by radiographic evaluation. Clinical or radiographic evidence of metastatic disease to regional peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. For the colorectal carcinoma only: Up to 5 lung metastases are allowable, provided they are stable (or responding) in number and size for minimum of 2-mos of systemic chemo and are amenable to SBRT.
• Microsatellite instability (MSI) or Mismatch repair deficiency (MMR-D)
• Prior radiation to the liver, including external beam, SBRT, Y90. Prior radiation therapy to the pelvis is acceptable
• Bevacizumab (Avastin®) cannot be given concurrently with HAI FUDR. Patients can previously have received it with a minimum 6-week washout period
• Active infection, hepatic encephalopathy
• Clinical evidence of portal hypertension (ascites, gastroesophageal varices or portal vein thrombosis) are exclusions. Note: surgically-related ascites does not exclude the patient.
• Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of childbearing potential must have negative pregnancy test prior to surgery)
• If in the opinion of the treating investigator a patient has any serious medical problems which may preclude receiving this type of treatment
• Patients with history or known presence of primary CNS tumors, seizures not well-controlled with standard medical therapy; Patients with a history of stroke within 3 months or with substantial residual deficit, based on investigator discretion
• Serious or non-healing active wound, ulcer, or bone fracture
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the HAIP chemotherapy (i.e., investigational regimen)
• Patients with psychiatric illness or social situations that would limit compliance with study requirements. Examples: active substance abuse, active severe alcohol abuse, etc.
• Inability to reliably commit to traveling to either Lexington, KY (for patients choosing TO site for HAI administration) or local CO site every 2 weeks for duration of the study treatment (6 months). Patient must have readily identifiable, reliable primary and back-up modes of transportation regardless of weather.
• Patients with AXIOS™ stents (or similar) used to connect the small intestine to the gastric remnant after a prior gastric bypass for access for ERCP/stent in the setting of biliary obstruction are eligible at the discretion of the investigator. Considerations regarding eligibility comprise removal of the stent prior to HAIP implantation, or the placement of the HAIP catheter at least 5cm away from the AXIOS stent.