Pressure-enabled Delivery in Radioembolization (TriNav Study)

A Prospective, Randomized, Open-Label Study to Examine The Effects of a Pressure-Enabled Drug Delivery Device on Radiotracer Distribution Compared to a Standard Microcatheter in the Context of Radioembolization

The purpose of the study is to determine if the type of catheter used in the mapping procedure prior to radioembolization improves the delivery of radioactivity to tumor(s) in participants with liver cancer.

The name of the devices involved in this study are:

• Pressure Enabled Drug Delivery (PEDD)/TriNav Infusion System
• Standard 2.4F microcatheter, not otherwise specified

This is a prospective, randomized, open-label, single-center, investigator-initiated study to determine if the type of catheter used to deliver the radiotracer in the mapping procedure improves the delivery of radioactive microspheres during radioembolization treatment for liver cancer.

Both catheters being used, the Pressure Enabled Drug Delivery (PEDD)/TriNav Infusion System and theStandard 2.4F microcatheter have been cleared for clinical use by the U.S. Food and Drug Administration.

Radioembolization for the treatment of liver tumors typically requires 2 separate procedures. The first procedure is called the mapping procedure. During the mapping procedure, the blood supply to the liver and tumor are evaluated with a type of x-ray called angiography. Once the optimal catheter position is determined for treatment, a "simulation" run is performed with the injection of a fluid that acts like the radiation that will be delivered to treat the tumors. This fluid is called a radiotracer. The study is looking to learn if the Pressure Enabled Drug Delivery device increases the ratio of radiotracer delivered to liver tumor tissue relative to normal liver tissue compared to a standard microcatheter. An improved delivery of radiotracer may indicate improved delivery of radioactive microspheres which may lead to improved tumor response rates and less liver toxicity

The research study procedures include assessments for eligibility, study treatment including evaluations, and follow-up visits.

Participants will undergo the study procedures in the normal course of their radioembolization procedure, with the addition of a second mapping procedure on the treatment day. Participants will be randomly assigned to one of two mapping procedures: Sequence A or Sequence B.

It is expected that about 10-20 people in total will take part in this research study.

TriSalus Life Sciences, Inc., a biotechnology and medical device company, is supporting this research study by providing funding.

Inclusion Criteria:

• Known HCC or CLM that are not amenable to curative resection or thermal ablative techniques such as microwave ablation.

• Prior clinical decision for treatment by radioembolization.

• Disease that is visible on CT or MRI as well as measurable disease in the liver. Measurable is defined as at least one lesion in the expected treatment field that can be accurately measured in at least one dimension (longest diameter) as (≥1 cm) with CT scan or MRI.

• Age ≥18 years. Because there is limited data with respect to radioembolization in patients <18 years of age with respect to tumor dosimetry and associated adverse events participants <18 years of age, children are excluded from this study.

• ECOG performance status < 2 (Karnofsky ≥60%, see Appendix A).

• Life expectancy >16 weeks.

• Suitable target artery diameter(s), defined in the TriNav labelling as 1.5 to 3.5mm vessels, based upon pre-procedural imaging.

• Adequate organ and marrow function as defined below:

  • International Normalized Ratio (INR): ≤ 1.5
  • Hemoglobin: ≥ 8.5 g/dL
  • Leukocytes: ≥2,000/mcL
  • Absolute neutrophil count: ≥1,00/mcL
  • Platelets: ≥50,000/mcL(after transfusion, if necessary)
  • Total bilirubin: ≤2.0 mg/dL
  • Albumin: ≥3 g/dL
  • AST(SGOT)/ALT(SGPT): ≤6 × institutional ULN
  • Glomerular filtration rate (GFR): 30 mL/min/1.73 m2

• Child Pugh Score A, or B7 with bilirubin ≤ 2 mg/dL.

• If extrahepatic disease is present (e.g. brain metastases), such disease must be stable, under treatment, or not an imminent threat to the patient's life or quality of life.

• Ability to understand and the willingness to sign a written informed consent document.

• Prior to study entry women of child-bearing potential must agree to not become pregnant, nurse a baby, or use any milk expressed for 2 weeks following radioembolization. Men must agree to not father a baby for 2 months after treatment with radioembolization (This is confirmed during the consenting process and documented when the patient signs the informed consent form. The effects of Yttrium-90 and radiation associated with the procedures, radiotracers, and subsequent imaging are known to have teratogenic effects on the developing human fetus. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother breastfeeding should be discontinued for the duration of study participation.)

• For HCC patients: Barcelona Clinic Liver Cancer Stage: A, B, C.

Exclusion Criteria:

• Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Unresolved toxicities related to cancer therapy that the investigator will continue and compromise patient safety.
• History of hepatic encephalopathy; history of severe peripheral allergy or intolerance to contrast agents, narcotics, sedatives, or atropine that cannot be managed medically.
• Uncontrolled intercurrent illness.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Prior external beam radiation treatment to the liver or prior intra-arterial liver-directed therapy including transarterial bland embolization, chemoembolization or radioembolization.
• Contraindications to angiography and selective visceral catheterization, including bleeding diathesis or uncorrectable coagulopathy.
• > 50% of tumor involvement of the liver.
• Receipt of intervention for the Ampulla of Vater or compromise thereof.
• Child-Pugh B8 or greater.
• Evidence of thrombosis in the main portal vein.
• For CLM patients: evidence of cirrhosis or portal hypertension.
• For CLM: Clinically-evident ascites other than trace noted on imaging.