Stereotactic Arrhythmia Radioablation for Ventricular Tachycardia (StAR-VT)

NCT ID: NCT05258422

Last Updated: 2025-03-18

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2031-12-31

Brief Summary

In 2017 a novel treatment approach to a series of 5 patients with refractory VT was introduced, using ablative radiation with a stereotactic body radiation therapy (SBRT) technique to arrhythmogenic scar regions defined by noninvasive cardiac mapping. More recently, Robinson et al. reported on the results of their Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia (ENCORE-VT) trial, also using a similar SBRT technique in a series of 17 patients with refractory VT. Both studies report a marked reduction in VT burden, a decrease in antiarrhythmic drug use, and an improvement in quality of life. Since then, numerous other centres have detailed their initial experience with this technique. These initial results suggest that this new treatment paradigm has the potential to improve morbidity and mortality for patients suffering from treatment-refractory VT by means of a minimally invasive technique, but requires further validation for widespread use.

The appropriate dose for therapeutic effect of this new treatment is not well established as only a single dose prescription of 25 Gy in 1 fraction has been described with benefit. In this phase 2 trial, the investigators plan on expanding the experience with this technique but also by contributing to understanding the relationship between dose-effect relationship through a dose de-escalation stratification, to 20 Gy in 1 fraction, with the goal of minimizing possible adverse events and radiation dose to surrounding healthy tissue while maintaining a clinical benefit.

Detailed Description

Ventricular tachycardia (VT) is a potentially life-threatening arrhythmia characterized by electrical re-entry within patches of heterogeneous myocardial fibrosis leading to sustained consecutive ventricular beats at a rate > 100 per minute. VT is classified based on hemodynamic stability, duration (less than or greater than 30 seconds), morphology (monomorphic or polymorphic), and mechanism (scar-related re-entry, automaticity, triggered activity.

In patients with monomorphic VT, implantable cardioverter-defibrillators (ICDs) have become the cornerstone of therapy in decreasing mortality, through the prevention of sudden death from potentially lethal sustained arrhythmia in select patients. However, ICDs have no effect on the underlying arrhythmogenic substrate or fibrotic scar and thus are primarily a symptom-control therapy; patients may develop recurrent and debilitating shocks associated with an increase in mortality. Currently, catheter ablation (CA) for VT is used as an adjunctive therapy for patients who are refractory to medical therapy. A recent systematic review and meta-analysis of randomized controlled trials and observation studies comparing medical therapy and catheter ablation for VT shows that CA is superior to medical therapy for scar-related VT with respect to VT recurrence and the life-threatening VT storm. Despite this, there is still a high reported incidence of VT recurrence in both medically-treated (48%) and ablation-treated (39%) patients, suggesting that the current treatment paradigm is suboptimal for good control of this debilitating arrhythmia.

In 2017, Cuculich et al. introduced a novel treatment approach to a series of 5 patients with refractory VT, using ablative radiation with a stereotactic body radiation therapy (SBRT) technique to arrhythmogenic scar regions defined by noninvasive cardiac mapping. More recently, Robinson et al. reported on the results of their Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia (ENCORE-VT) trial, also using a similar SBRT technique in a series of 17 patients with refractory VT. Both studies report a marked reduction in VT burden, a decrease in antiarrhythmic drug use, and an improvement in quality of life. These initial results suggest that this new treatment paradigm has the potential to vastly improve morbidity and mortality for patients suffering from VT by means of a minimally invasive technique, but requires further validation for widespread use.

Additionally, the appropriate dose for therapeutic effect of this new treatment is not well established as only a single dose prescription of 25 Gy in 1 fraction has been described with benefit. In this phase 2 trial, the investigators plan on expanding the experience with this technique but also by contributing to understanding the relationship between dose-effect relationship through a dose de-escalation stratification, to 20 Gy in 1 fraction, with the goal of minimizing possible adverse events and radiation dose to surrounding healthy tissue while maintaining a clinical benefit.

Conditions

Ventricular Tachycardia; Arrhythmia; Arrhythmic Storm; Radiation Toxicity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiation: 20 Gy in 1 fraction

External beam, stereotactic body radiotherapy of 20 Gy delivered in 1 fraction to the planning target volume (PTV) of the arrhythmogenic substrate

Group Type: EXPERIMENTAL

stereotactic body radiotherapy, 20 Gy in 1 fraction

Intervention Type: RADIATION

A single dose of focused radiation therapy of 20 Gy in 1 fraction to the PTV of the arrhythmogenic substrate

Interventions

stereotactic body radiotherapy, 20 Gy in 1 fraction

A single dose of focused radiation therapy of 20 Gy in 1 fraction to the PTV of the arrhythmogenic substrate

Intervention Type: RADIATION

Other Intervention Names

stereotactic ablative radiotherapy, 20 Gy in 1 fraction

Eligibility Criteria

Inclusion Criteria

• 18 years of age
• Ishemic or non-ischemic cardiomyopathy
• Recurrent episodes of monomorphic ventricular tachycardia having failed standard treatment with at least 1 antiarrhythmic drug
• Previous endocardial and/or epicardial electrophysiology study and ablation.

Participants who have a contraindication to electrophysiology studies (ventricular thrombus, absence of vascular access, valvular heart disease or mechanical heart valve that precludes left-ventricular access) may be eligible for the protocol provided the arrhythmic substrate can be defined through non-invasive methods.

Exclusion Criteria

• Previous RT in the treatment field that precludes furth RT
• Active connective tissue disease
• Interstitial pulmonary fibrosis
• Pregnant or breastfeeding individuals
• Participants who plan to become pregnant or breast feed during the study duration

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Joanne Alfieri

Associate Professor Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joanne Alfieri, MD

Role: PRINCIPAL_INVESTIGATOR

MUHC division of radiation oncology/RIMUHC

Martin L Bernier, MD

Role: PRINCIPAL_INVESTIGATOR

MUHC division of cardiology

Locations

Cedars Cancer Center, McGill University Health Centre

Montreal, Quebec, Canada

Countries

Canada

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Related Links

https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm

CTCAE v5.0

Other Identifiers

2022-7202

Identifier Type: -

Identifier Source: org_study_id