Phase I/II Randomized Study of Stereotactic Ablative Radiotherapy (SABR) Versus Standard of Care for Refractory Structural Cardiac Arrhythmias (SABR-HEART)

Cardiac Arrhythmia Clinical Trial

Official title: Phase I/II Randomized Study of Stereotactic Ablative Radiotherapy (SABR) Versus Standard of Care for Refractory Structural Cardiac Arrhythmias (SABR-HEART)

Status Withdrawn

Clinical Trial Summary

Phase I: For the Phase I portion, there will be up to 15 patients treated with SABR and followed for 6 months post-treatment to ensure no significant acute grade 3 or 4 toxicity from SABR treatment. Efficacy as defined below will also be assessed. Following this Phase I lead-in, results will be presented to the FDA for review. Only upon favorable analysis by the FDA committee, and with written explicit permission, will the Phase II randomized portion ensue. This is to act as a safety and efficacy safeguard and has is addressed more thoroughly in the Statistical Analysis Plan of this protocol.

Phase II: A 1:1 randomized Phase II portion with 25 patients in each arm assigned to SABR or current practice (standard of care; Figure 3). Standard of care is defined as nationally recognized appropriate next treatment strategies for medical and catheter-ablation refractory structural cardiac VT that is assessed and judged appropriate for the patient by his/her treating cardiologist. This includes repeat catheter ablation (intravascular and/or epicardial catheter ablation), placement of left-ventricular assist device (LVAD), heart transplant, or further medical management (e.g. antiarrhythmic drug modulation/continuation). Randomization will be performed through the Clinical Trial Conduct (CTC) website.

Clinical Trial Description

Primary Objectives Phase I:

-Assess acute toxicity and efficacy with SABR in treating refractory structural cardiac ventricular tachyarrhythmias (VT). Ensure safety and treatment efficacy.

Primary Objectives Phase II:

• Investigate overall toxicity with SABR compared to next best management practices (standard of care) in treating refractory structural cardiac ventricular tachyarrhythmias (VT).

• Investigate VT episode reduction with SABR compared to standard of care to evaluate effectiveness and potential superiority of SABR to current day options.

Primary Objectives Phase I:

1. Assess acute toxicity and efficacy with SABR in treating refractory structural cardiac ventricular tachyarrhythmias (VT). Ensure safety and treatment efficacy.

Primary Objectives Phase II:

1. Investigate overall toxicity with SABR compared to next best management practices (standard of care) in treating refractory structural cardiac ventricular tachyarrhythmias (VT).

2. Investigate VT episode reduction with SABR compared to standard of care to evaluate effectiveness and potential superiority of SABR to current day options.

Secondary Objectives

The following endpoints will be analyzed retrospectively based on prospectively collected (event-free survival endpoints) and at the specified time points (e.g. QOL questionnaire). Participation in QOL assessment and bio specimen collection for secondary endpoints is completely voluntary and not mandated by the trial.

1. 6-month and 1-year overall survival (OS) of SABR compared to standard of care.

2. Quality of life (QOL) with SABR compared to standard of care (baseline and at 6 months after randomization).

3. Hospitalization-free survival with SABR compared to standard of care (evaluated at 1-year).

4. Cost-effectiveness analysis with SABR compared to standard of care (evaluated at 1-year).

5. Freedom-from Antiarrhythmic medications with SABR compared to standard of care (evaluated at 1-year).

6. Freedom-from Electrical Storm with SABR compared to standard of care (evaluated at 1-year).

7. Treatment-free Survival with SABR compared to standard of care (evaluated at 1-year).

8. Event-free Survival with SABR compared to standard of care (evaluated at 1-year).

9. Long term (>1year) toxicity with SABR compared to standard of care (evaluated at 1-year).

10. Ejection fraction improvement with SABR compared to standard of care (evaluated at 1-year).

11. Transplant/LVAD-free survival with SABR compared to standard of care (evaluated at 1-year).

12. Number, type, and treatment success and cycle length of ICD-treated VTs with SABR compared to standard of care (evaluated at 1-year).

13. Parameters obtained from cardiac imaging, and/or serum markers will be associated with frequency of survival, response to treatment, and toxicity at regular time intervals using cardiac ECHO, MRI, CT imaging, ICD interrogation, and/or serum/blood work studies for prognostic/predictive biomarker and radiomic identification. ;

Related Conditions & MeSH terms

• Arrhythmias, Cardiac
• Cardiac
• Cardiac Arrhythmia
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Tachyarrhythmias

• NCT number: NCT05084391
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: September 12, 2019
• Completion date: February 8, 2024