Stereotactic Ablative Radiotherapy for Refractory Ventricular Tachycardia

Study Overview
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Brief Summary
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Single arm, phase Ib/2a dose escalation study with an expansion cohort to determine the maximal tolerated dose (MTD) for stereotactic ablative radiotherapy of targets in the cardiac myocardium and to make a preliminary assessment of the efficacy of the treatment. The dose escalation will be guided by Time-to-Event Continual Reassessment Method (TITE-CRM) to ensure more patients will be spared dose limiting toxicities and more patients will be entered on the dose level that will be chosen as minimal dose of maximal effect. This design also allows for continual accrual of patients when delayed adverse events may be observed.

Official Title
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Stereotactic Ablative Radiotherapy (SABR) for Refractory Ventricular Tachycardia - a Phase I/II Study

Conditions
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Refractory Ventricular Tachycardia

Intervention / Treatment
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* Radiation: Stereotactic Ablative Radiotherapy (SABR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented sustained ventricular arrhythmias refractory to or not a suitable candidate for catheter based RFA ablative therapy Documented sustained ventricular arrhythmias refractory to or not a suitable candidate for cardiac sympathetic denervation therapy Documented ventricular arrhythmias refractory to or not a suitable candidate for cardiac transplantation Documented sustained ventricular arrhythmias refractory to or not a suitable candidate for additional medical management ICD in place with documented episodes recurrent VT despite best clinical management previous refusal of ICD with recurrent sustained ventricular arrhythmias If ischemic cardiomyopathy, myocardial infarction occurred more than one month prior to enrollment No history of prior radiotherapy to the chest Prescribed dose must be deliverable using SABR technique Age ≥ 18 years Karnofsky Performance Status (KPS) > 70 If a woman is of childbearing potential, a negative serum pregnancy test must be documented. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for at least 4 weeks after study treatment. Ability to understand and willingness to sign a written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic Ablation Treatment Arm<br>This is a single-arm, non-blinded study. | Radiation: Stereotactic Ablative Radiotherapy (SABR)<br>* A single fraction of radiation is delivered using a clinical radiotherapy system capable of stereotactic radiotherapy to the chest, with on-board image guided radiotherapy capabilities, respiratory motion management, and Intensity Modulated Radiotherapy Treatment (IMRT) planning.<br>* Other names: external beam radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICD (Implantable Cardioverter Defibrillator) Shock Free Survival | ICD (implantable cardioverter defibrillator) shock free survival at six months | 6 months | 
| Incidence of Salvage Definitive Anti-arrhythmia Therapy (Cardiac Transplant) | Incidence of salvage definitive anti-arrhythmia therapy (cardiac transplant) over 5 years. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Return of Ventricular Tachycardia Requiring Defibrillation, Intravenous Drug Therapy or Readmission to Hospital | Incidence of return of ventricular tachycardia requiring defibrillation, intravenous drug therapy or readmission to hospital over 5 years | 5 years | 
| Incidence of ICD Shocks | Incidence of ICD shocks 12 months post-SABR procedure | 12 months post-SABR procedure |