A Phase I/II Study of Cardiac Radioablation for Refractory Ventricular Tachycardia

This voluntary study is designed to learn what is the minimum dose of radiation therapy (RT) needed to successfully reduce the incidence of refractory ventricular tachycardia (VT) by half. Additionally, the study will examine the utility of target volume definition using Delayed Enhancement Cardiac MRI (DE-CMR). Radiation therapy, given in a highly focused single dose to a portion of the heart, by a non-invasive method, has been found to change the electrical conduction of the heart. This will be done with the goal of reducing the number of episodes of VT in people where invasive thermal (heat) ablation and heart medications have not completely worked.

Cardiac radioablation has been done at other institutions using a dose of RT that may be higher than needed to obtain the benefit of fewer episodes of VT. We are trying to learn if lower doses of RT will work to reduce VT. Cardiac radioablation is currently offered at a number of institutions worldwide at the standard dose of 25 Gray, or Gy (the unit of dose for radiation therapy) given in a single treatment. This study is testing if lower doses of RT are just as effective as 25 Gy. The doses being tested are 15 Gy (the dose that we will start at), 20 Gy and 25 Gy (if the lower doses are found not to work well).

Potential participants will be identified by their cardiologist. Electroanatomic mapping will have already been obtained as part of routine care. A Delayed Enhancement Cardiac MRI will be performed (if a new one is necessary) and a Radiation Therapy Simulation. Commercial RT software will be used to fuse the DE CMR and the RT Simulation treatment planning CT scan. The cardiologist and radiation oncologist will define the Gross Target Volume and the expansions for the Clinical and Planning Target Volumes. These volume definitions will be used by the Radiation Oncology Dosimetrist. The dose will be determined in standard 3+3 Phase I fashion. Dose escalation will proceed in a standard 3 + 3 Phase I fashion according to both dose limiting toxicity (DLT) and efficacy. Escalation will stop when there is efficacy 50% or greater without severe DLT or when there is severe DLT (2+ of 3 or 6 with DLT as per traditional 3 + 3 Phase I design). The dose will not be escalated within a single patient.

When the minimum effective dose (MED) or maximum tolerable dose (MTD) is determined, further accrual will occur at that dose level until 12 patients are accrued and observed for 14 weeks (6 week blanking and 8 week (56 day) evaluation).

DLT is defined as any grade 3 toxicity requiring hospitalization or any grade 4 - 5 toxicity (CTCAE v.5) determined to be treatment related (possibly, probably, or definitely related to study treatment) occurring within 14 weeks after treatment. DLT's occurring after the 14-week observation period may still impact on dose escalation.