Radioembolization With Intra-arterial Angiotensin II to Improve Tumor-absorbed Dose (RADIANT) (RADIANT)

Radioembolization With Intra-arterial Angiotensin II to Improve Tumor-absorbed Dose

This clinical trial will test whether a short infusion of a drug called angiotensin II (AT-II) can make a liver cancer treatment work better. The drug is given directly into the artery that supplies blood to the liver, right before a treatment called yttrium-90 (90Y) radioembolization.

The main questions it aims to answer are:

• Does angiotensin II help more of the radioactive beads reach the tumor and less reach the healthy parts of the liver?
• Is it safe to add angiotensin II to the standard radioembolization treatment? What will participants do?
• First visit (work-up): Participants will have the standard preparation for radioembolization. A small test dose of radioactive tracer technetium 99mTc macroaggregated albumin (99mTc-MAA) will be injected into the liver through an artery. On the same day, a single-photon emission computed tomography (SPECT)/CT scan will be performed to see how the tracer distributes in the liver and if there are depositions outside the liver. If everything looks good, the participant will return for treatment in 2-3 weeks.
• Second visit (treatment): Participants will receive the actual radioembolization treatment. At each injection site in the liver, first angiotensin II is administered, immediately followed by the injection of the radioactive beads (90Y microspheres). If the treatment requires injections in multiple locations, the participant will receive angiotensin II at each spot.
• After treatment: Participants will receive a Positron Emission Tomography (PET)/CT scan so the research team can see where the radioactive beads went. This will be compared to the distribution of the radioactive tracer (99mTc-MAA) from the first SPECT/CT scan (performed without angiotensin II) to measure how much angiotensin II helped target the tumor.

All monitoring (including blood pressure, heart rate, oxygen saturation, and breathing rate) takes place during the procedure as part of routine care, and there are no extra hospital visits beyond what is normally required for radioembolization.

Study Overview

• Status: Recruiting
• Conditions: Liver Cancer Adult; Liver Cancer (Locally Advanced or Metastatic)
• Intervention / Treatment: Drug: Angiotensin II (Giapreza®); Radiation: Yttrium-90 radioembolization

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Niek Wijnen, MD; Phone Number: +31652022145; Email: n.wijnen-5@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht
    • Utrecht, Utrecht, Netherlands, 3584 CX
      • Recruiting
      • University Medical Center Utrecht
      • Contact: Niek Wijnen, MD; Phone Number: +31652022145; Email: n.wijnen-5@umcutrecht.nl
      • Principal Investigator: Maarten L.J. Smits, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Patients diagnosed with primary or metastatic liver tumors (any histological type).
• A clinical indication for radioembolization.
• Liver tumors with a diameter ≥ 2 cm.
• Age ≥ 18 years.
• Competent and able to provide own informed consent (no legally designated representative).
• Written informed consent.

Exclusion criteria:

• Any serious comorbidity preventing the safe administration of angiotensin II (AT-II). This includes:

  1. Uncontrolled hypertension.
  2. Treatment with ≥ 3 antihypertensive drugs.
  3. Arterial (cerebro-)vascular or venous thromboembolic event within the past 6 months.
• Current use of angiotensin-converting enzyme (ACE) inhibitors.
• Current use of angiotensin II receptor blockers (ARBs).
• Known hypercoagulable state (i.e., thrombophilia).
• History of severe peripheral vascular disease.
• Known hypersensitivity to the active substance in Giapreza: angiotensin II.
• Known hypersensitivity to any of the excipients in Giapreza: mannitol, sodium hydroxide or hydrochloric acid.
• Any serious and/or chronic liver disease preventing the safe administration of radioembolization.
• Uncorrectable extrahepatic deposition of scout dose activity; activity in the falciform ligament, portal lymph nodes, and gallbladder is accepted.
• Pregnancy or breastfeeding.
• Body weight over 150 kg (because of maximum table load).
• Known severe allergy to intravenous contrast fluids.
• Participation in another investigational study which may compromise any endpoint of the study.
• Any other significant comorbidity or medical condition that may compromise the safety of radioembolization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radioembolization with intra-arterial angiotensin II; Single-arm study in which all participants undergo standard yttrium-90 (⁹⁰Y) radioembolization for primary or metastatic liver tumors. During the therapeutic radioembolization procedure, angiotensin II is administered intra-arterially immediately prior to ⁹⁰Y glass microsphere injection at each arterial injection position.

Drug: Angiotensin II (Giapreza®); Angiotensin II is administered intra-arterially into the hepatic artery during the therapeutic radioembolization procedure. After confirmation of correct microcatheter position, angiotensin II is infused at a dose of 10 µg/min for 100 seconds, immediately followed by injection of yttrium-90 glass microspheres (TheraSphere®). In participants with multiple arterial injection positions, angiotensin II is administered at each injection position. In cases where whole-liver treatment is performed in two separate sessions, angiotensin II is administered during both treatment sessions. Dose: 10 µg/min Duration of Administration: 100 seconds per injection position Route of Administration: Intra-arterial (hepatic artery); Radiation: Yttrium-90 radioembolization; Selective intra-arterial administration of yttrium-90 glass microspheres for the treatment of primary or metastatic liver tumors, performed according to standard clinical protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor-to-non-tumor ratio (TNR) improvement factor	The tumor-to-non-tumor ratio (TNR) improvement factor is defined as the ratio of the TNR measured after yttrium-90 (⁹⁰Y) radioembolization with intra-arterial angiotensin II infusion to the TNR measured during the standard work-up procedure without angiotensin II. TNR after treatment is quantified using post-radioembolization (⁹⁰Y) Positron Emission Tomography (PET)/CT imaging. Baseline TNR is quantified using technetium-99m macroaggregated albumin (⁹⁹ᵐTc-MAA) single-photon emission computed tomography (SPECT)/CT imaging obtained during the work-up procedure. TNR values represent the ratio of microsphere activity concentration in tumor tissue relative to non-tumorous liver parenchyma.	From work-up procedure (baseline ⁹⁹ᵐTc-MAA SPECT/CT) to post-treatment imaging following radioembolization (⁹⁰Y PET/CT), within approximately 2-3 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success of intra-arterial angiotensin II administration	Technical success is defined as the successful intra-arterial administration of angiotensin II at a dose of 10 µg/min for 100 seconds at the intended hepatic arterial injection position(s), followed immediately by delivery of yttrium-90 glass microspheres.	During the therapeutic radioembolization procedure.
Safety, as evaluated by the absence of adverse events, of intra-arterial angiotensin II infusion combined with radioembolization.	Assessment of adverse events related to intra-arterial angiotensin II infusion in combination with yttrium-90 radioembolization. Adverse events are graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Safety evaluation includes hemodynamic effects (e.g., changes in blood pressure, heart rate), procedural complications, and any other treatment-emergent adverse events.	From start of angiotensin II infusion during the therapeutic procedure until completion of post-procedural monitoring (up to 1 week after the procedure).

Collaborators and Investigators

• Sponsor: Niek Wijnen
• Collaborators: PAION Deutschland GmbH

Publications and helpful links

General Publications

• van den Hoven AF, Smits ML, Rosenbaum CE, Verkooijen HM, van den Bosch MA, Lam MG. The effect of intra-arterial angiotensin II on the hepatic tumor to non-tumor blood flow ratio for radioembolization: a systematic review. PLoS One. 2014 Jan 17;9(1):e86394. doi: 10.1371/journal.pone.0086394. eCollection 2014.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 16, 2025
• First Posted (Actual): December 31, 2025

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Radioembolization; Angiotensin II; yttrium-90
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neoplastic Processes; Carcinoma; Pathological Conditions, Signs and Symptoms; Carcinoma, Hepatocellular; Neoplasm Metastasis; Liver Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Biological Factors; Autacoids; Inflammation Mediators; Angiotensins; Giapreza; Angiotensin II
• Other Study ID Numbers: 24U-0008; 2025-521870-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are not able to share the data with other researchers due to privacy reasons, as this will not be explicitly requested from the patients during the informed consent procedure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No