Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Phase I Study Evaluating Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
2 other identifiers
interventional
20
1 country
1
Brief Summary
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. ...
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2026
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 18, 2026
CompletedFirst Posted
Study publicly available on registry
July 21, 2026
CompletedStudy Start
First participant enrolled
August 5, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2029
Study Completion
Last participant's last visit for all outcomes
December 31, 2031
July 31, 2026
July 21, 2026
3.4 years
July 18, 2026
July 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
The safety of the study therapy will be evaluated by the maximum dosage at which no more than 1 of 6 participants experience DLT during DLT period (Cycle 1) and by reporting the grade and type of toxicity at each dose level
DLT assessment will occur during Cycle 1 (28 days total).Assessment of adverse events will occur from the first study intervention through 28 days after the last study intervention or initiation of a new anti-cancer treatment whichever comes first
Secondary Outcomes (1)
Establish the Overall Response Rate (ORR), defined as complete response (CR) + partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST)
Assessed based on imaging studies prior to starting cycles 1, 3 and 5, Day 28 Safety visit, and 3-month Follow Up visit
Study Arms (1)
1/Phase I
EXPERIMENTALParticipants with liver metastatic disease will receive continuous administration of carfilzomib via Hepatic Artery Infusion Pump (HAIP)
Interventions
Variable doses, continuously administered via Hepatic Artery Infusion Pump (HAIP) for up to 6 cycles
Eligibility Criteria
You may qualify if:
- Participants must have a histologically or cytologically confirmed by pathology report diagnosis of colorectal cancer (CRC), intrahepatic cholangiocarcinoma (ICC), or adrenocortical carcinoma (ACC).
- Participants must have measurable liver-dominant metastatic disease. Note: liver-dominant metastatic disease is defined as \>=75% of metastatic disease present in the liver as assessed by the principal investigator.
- Extrahepatic disease should be treated with anticancer therapy, if applicable, and should be stable by RECIST criteria for at least 6 weeks prior to study treatment initiation.
- Participants must have previously undergone hepatic artery infusion pump therapy and have a functioning hepatic artery infusion pump in place.
- Participants must have progressed on, been intolerant of, or have residual disease after HAI floxuridine and appropriate current standard-of-care treatment.
- Age \>= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status \<= 2.
- Participants must have an adequate organ and marrow function as defined below:
- Leukocytes \> 3,000/mcL
- Hemoglobin \>= 9 mg/dL
- Absolute neutrophil count \> 1,500/mcL
- Platelets \> 100,000/mcL
- Total bilirubin \< 2 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) \< 2.5 X institutional (ULN)
- Alanine aminotransferase (ALT) \< 2.5 X institutional (ULN)
- +8 more criteria
You may not qualify if:
- Participants with liver metastases amenable to resection.
- Participants who received floxuridine within 6 weeks prior to the study treatment initiation.
- Participants who received any anticancer therapy within 2 weeks prior to the study treatment initiation.
- Participants who received any investigational agents within 4 weeks prior to the study treatment initiation.
- Participants with incontrovertible radiographic evidence of disease progression per the RECIST definition outside of the liver within 3 months prior to the study treatment initiation. Note: Pulmonary lesions less than 1 cm are allowed.
- Prior radiation to the liver (Yttrium-90 \[Y-90\] or External Beam Radiation Therapy \[EBRT\]).
- History of allergic reactions attributed to compounds of similar chemical composition to CFZ.
- Positive serum or urine Beta-human chorionic gonadotropin (Beta-HCG) pregnancy test performed at screening.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, evaluated by medical history, electrocardiogram (EKG), physical exam, and laboratory testing, or social situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study or that would limit compliance with study requirements.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (4)
Larrain CM, Victory JH, Desai PP, Friedman LR, Stepp H, Ashe R, Remmert K, Sinha S, Smith EC, Russell N, Pu T, Eade AV, Burke JF, Ho J, Yaffe MB, Kleiner DE, Schmidt K, Figg WD, Hernandez JM. A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion. JCI Insight. 2025 Nov 4;10(24):e199200. doi: 10.1172/jci.insight.199200. eCollection 2025 Dec 22.
PMID: 41196694BACKGROUNDJun Y, Xu J, Kim H, Park JE, Jeong YS, Min JS, Yoon N, Choi JY, Yoo J, Bae SK, Chung SJ, Yeo Y, Lee W. Carfilzomib Delivery by Quinic Acid-Conjugated Nanoparticles: Discrepancy Between Tumoral Drug Accumulation and Anticancer Efficacy in a Murine 4T1 Orthotopic Breast Cancer Model. J Pharm Sci. 2020 Apr;109(4):1615-1622. doi: 10.1016/j.xphs.2020.01.008. Epub 2020 Jan 13.
PMID: 31945310BACKGROUNDZeng TM, Jiang TY, Yang G, Cheng Z, Lou C, Wei W, Tao CJ, Hu S, Wang H, Cui XW, Tan YX, Dong LW, Wang HY, Yuan ZG. Bortezomib in previously treated phosphatase and tension homology-deficient patients with advanced intrahepatic cholangiocarcinoma: An open-label, prospective and single-centre phase II trial. Clin Transl Med. 2024 May;14(5):e1675. doi: 10.1002/ctm2.1675.
PMID: 38689424BACKGROUNDTilk S, Frydman J, Curtis C, Petrov DA. Cancers adapt to their mutational load by buffering protein misfolding stress. Elife. 2024 Nov 25;12:RP87301. doi: 10.7554/eLife.87301.
PMID: 39585785BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jonathan M Hernandez, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 18, 2026
First Posted
July 21, 2026
Study Start (Estimated)
August 5, 2026
Primary Completion (Estimated)
December 31, 2029
Study Completion (Estimated)
December 31, 2031
Last Updated
July 31, 2026
Record last verified: 2026-07-21
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
- Access Criteria
- Clinical data will be made available upon request and with the permission of the study PI.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.