Hybrid hospital and community delivery of hepatic artery infusion chemotherapy for liver metastases and intrahepatic cholangiocarcinoma

Phase IIa Study of Safety/Feasibility of a Hybrid Model of Tertiary and Community Delivery of Hepatic Artery Infusion Chemotherapy

This Phase 2 trial will test whether giving floxuridine through a surgically implanted hepatic artery infusion pump — with follow-up care either at a major hospital or by local community oncologists — is safe and practical for adults with colorectal cancer liver metastases or unresectable intrahepatic cholangiocarcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: University of Kentucky (Academic / other)
• Drugs / interventions: Bevacizumab, chemotherapy, radiation
• Locations: 1 site (Lexington, Kentucky)
• Trial ID: NCT07201519 on ClinicalTrials.gov

What this trial studies

This Phase 2 study implants a hepatic artery infusion pump to deliver floxuridine directly to the liver in adults with colorectal cancer liver metastases (resectable or unresectable) or unresectable intrahepatic cholangiocarcinoma. After pump placement, participants receive liver-directed chemotherapy for about 3–4 months and are managed either at the coordinating hospital or through a community oncologist close to home. The trial measures safety outcomes related to pump implantation and infusion, and feasibility outcomes related to performing routine pump refills and follow-up outside the tertiary center. Key endpoints include procedural complications, adverse events during infusion, and logistics/retention comparisons between hospital and community delivery.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed colorectal adenocarcinoma limited to the liver (resectable or unresectable per protocol) or unresectable intrahepatic cholangiocarcinoma with less than 70% liver involvement, ECOG 0–1, and acceptable blood counts and liver function are the intended candidates.

Not a fit: Patients with widespread extrahepatic metastatic disease, extensive liver involvement beyond protocol limits, poor performance status (ECOG ≥2), or who cannot undergo pump surgery are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could allow effective liver-directed chemotherapy while reducing travel and increasing access to care by letting patients receive pump refills closer to home.

How similar studies have performed: Prior single-center series have shown hepatic artery infusion of floxuridine can control liver metastases, but structured hybrid models that shift routine pump refills to community providers remain relatively novel and less studied.

Eligibility criteria

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.

Where this trial is running

Lexington, Kentucky

• University of Kentucky — Lexington, Kentucky, United States (Recruiting)

Study contacts

• Principal investigator: Michael Cavnar, MD — University of Kentucky
• Study coordinator: Yvonne Taul, RN

Conditions Colorectal Cancer Metastatic; Intrahepatic Cholangiocarcinoma; hepatic artery infusion; chemotherapy; floxuridine