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

Phase 2RecruitingNCT07312292

Niek Wijnen15 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Interventions

Angiotensin II (Giapreza®)DRUG

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)

Yttrium-90 radioembolizationRADIATION

Selective intra-arterial administration of yttrium-90 glass microspheres for the treatment of primary or metastatic liver tumors, performed according to standard clinical protocol.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: From work-up procedure (baseline ⁹⁹ᵐTc-MAA SPECT/CT) to post-treatment imaging following radioembolization (⁹⁰Y PET/CT), within approximately 2-3 weeks.

Secondary Outcomes

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.

Time frame: From start of angiotensin II infusion during the therapeutic procedure until completion of post-procedural monitoring (up to 1 week after the procedure).

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.

Time frame: During the therapeutic radioembolization procedure.