Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy

Adrenocortical Carcinoma, Colorectal Neoplasms, Intrahepatic Cholangiocarcinoma, Metastasis, Neoplasm, Neoplasms

Hepatic artery infusion, Carfilzomib, Colorectal Cancer, Intrahepatic cholangiocarcinoma, Adrenocortical Cancer, Measurable liver metastasis

Background: Cancers that begin in the colon, adrenal glands, or bile ducts may spread to the liver. These liver tumors are often treated using a hepatic artery infusion (HAI) pump. The HAI pump is installed in the artery that goes to the liver; drugs are administered directly to the liver through this pump. But these tumors often return after treatment. Carfilzomib (CFZ) is a drug approved to treat another kind of cancer. Researchers want to find out if this drug may be helpful when administered through the HAI pump directly to the liver for people with colon, adrenal glands, or bile duct cancer that has spread to the liver. Objective: To test the safety of carfilzomib (CFZ) delivered via a hepatic artery infusion (HAI) pump directly to the liver in people with cancer in their liver. Eligibility: People aged 18 years or older with cancers of the colon, adrenal glands, or bile ducts that spread to the liver and persist after treatment. They must have a functioning hepatic artery infusion (HAI) pump in place from previous treatment of HAI pump therapy. Design: Participants will be screened. They will have a physical exam, blood tests, imaging scans, and a test of their heart function. They will also have a test to show how the blood flows through their liver: A radioactive substance will be injected into a vein, and a special camera will take pictures of the blood flow for up to 1 hour. Participants will receive the study drug for about 6 months. They will visit the clinic once a week. Their HAI pump will be filled with the drug at each visit; the drug will slowly drain from the pump into the liver. Blood tests and imaging scans will be repeated during the study. Participants will have follow-up visits 1 and 3 months after their last dose of study drug. An optional liver biopsy (tissue sample) for research purposes may be done before the study drug is given, and again (optional) within 28 days after first receiving the study drug. Individuals may participate in the study even if they do not agree to have the biopsies done. ...

Background: * Targeting protein homeostasis with proteasome inhibitors has demonstrated excellent efficacy across multiple pre-clinical cancer models, although translation to patients with solid tumors has consistently failed to yield meaningful responses secondary to new protein synthesis rebound associated with intermittent dosing. * Implantable pumps for outpatient continuous infusion were developed and culminated in a commercialized product in 1980, though the only drug used to date is floxuridine. * Carfilzomib (CFZ), a second-generation irreversible 20S core particle proteasome inhibitor, can be delivered by the hepatic artery infusion pump to diminish extra-hepatic systemic clearance and feasibly direct a larger percentage of the total dose to the desired tissues at continuous concentrations. Objective: -To establish the safety of hepatic artery infusion (HAI) of carfilzomib (CFZ) in participants with liver metastatic disease who were previously treated with HAI pump therapy Eligibility: * Participants with colorectal cancer (CRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC) with liver metastatic disease not amenable to resection * Participants must have been treated with HAI floxuridine and already have a surgically inserted HAI pump in place * Age \>= 18 years * Adequate organ function Design: * Open-label, single-center, non-randomized Phase I study * Treatment with HAI infusion of CFZ will be delivered in cycles of 28 days for up to 6 cycles.

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