Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia

Patients with Ventricular Tachycardia (VT) who have failed standard therapy (medicines,
invasive catheter ablation) have limited options, with one-year survival below 20%.
Preclinical data demonstrate that single fraction stereotactic body radiotherapy (SBRT) to
discrete portions of the heart is feasible and may result in a reduction or elimination of
VT. The efficacy may be further improved when guided by cardiac electrophysiologic (EP)
testing. In total, the mapping and ablation proposed for this EP-guided Noninvasive Cardiac
Radioablation (ENCORE) is a rapid and totally non-invasive method. Overall safety and early
efficacy of ENCORE have not been rigorously studied in a prospective trial to-date. The
purpose of this phase I/II study is to demonstrate the short-term safety and preliminary
efficacy of ENCORE for patients with life-threatening, treatment-refractory VT.

Inclusion Criteria:

1. DOCUMENTED VT:

1. Patient must have documented sustained monomorphic ventricular tachycardia as
documented on either a 12-lead ECG or intracardiac ICD interrogation — OR—

2. Monomorphic PVCs documented on a 12-lead ECG.

2. ANTIARRHYTHMIC MEDICATION: Patient must have failed or become intolerant to at least
one antiarrhythmic medication (amiodarone, sotalol, or mexiletine).

-AND—

3. CATHETER ABLATION: Patient must have failed at least one invasive catheter ablation
procedure, or have a contraindication to a catheter ablation procedure (e.g., LV
thrombus, severe pulmonary disease), or have VT thought to arise from a protected
location (e.g., epicardial VT with history of previous cardiac surgery).

4. MINIMUM VT BURDEN: Patient must have either:

1. At least 3 VT episodes (sustained VT, ICD ATP or ICD shock) over previous 6
months prior to enrollment

-OR—

2. >20% PVC burden with a cardiomyopathy (LVEF<50%)

5. Patient must be deemed medically fit for stereotactic body radiation therapy by the
treating physician.

6. Patient must be > 18 years old.

7. Patient must be able to understand and be willing to sign an IRB approved written
informed consent document.

Exclusion Criteria:

1. Patient must not have past history of radiotherapy within the projected treatment
field.

2. Advanced symptomatic heart failure as defined as NYHA Class IV heart failure (inotrope
dependent and/or current left-ventricular assist device (LVAD))

3. Polymorphic VT or ventricular fibrillation (VF) as a clinical heart rhythm (as
determined by 12-lead ECG and/or ICD interrogation).

4. More than 3 distinct clinical VT morphologies observed (ECG or ICD interrogation or
invasive EP study) OR more than 5 distinct induced VT morphologies during ECGI
testing.

5. Advanced myocardial scar substrate that would require stereotactic delivery to a
target volume deemed unsafe by the treating physician.

6. Unlikely to live 12 months, in the absence of VT, as best based on clinical judgment
by the treating and enrolling physicians.

7. Patient must not be pregnant and/or breastfeeding and must have a negative pregnancy
test within 14 days of study entry.