Clinical trial NCT06743789: Trial in Arrhythmia Radioablation for Ventricular Tachycardia: Single Fraction vs Three Fractions
Official title: Dose De-escalation Randomized Phase I/II Trial in Arrhythmia Radioablation for Ventricular Tachycardia: Single Fraction vs Three Fractions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ventricular Tachycardia
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
First posted: 2024-12-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: If participants are randomized to either Arm 1 or Arm 2, participants will be in one of the three groups. Each group will enroll 3 participants, based on a criteria of consecutive enrollment over time. After 6 weeks from the last treated participant in Group 1, there will be a review of safety and efficacy of the study intervention in the treated participants before enrolling participants in the next group. This review will continue until the 3rd participant in Group 3 is enrolled and treated. Subsequently the protocol will then move into the follow up phase.
Primary purpose: TREATMENT

Brief summary: This is a research study that aims to understand if giving a lower dose of treatment all at once is as effective and safe as dividing it into three smaller doses for patients with a heart condition called refractory ventricular tachycardia (VT). These patients have not exhibited positive responses to conventional medications or procedures. This study aims to explore whether an alternative approach could yield more beneficial outcomes.

Detailed description: Ventricular tachycardia (VT) is a life-threatening heart rhythm disorder that arises from areas of diseased tissue in the heart. Treatment of VT can involve anti-arrhythmic drugs and catheter-based ablations. Unfortunately, despite multiple antiarrhythmic drugs, as well as the catheter-based ablation procedures, VT continues to persist in your case. At this point in time, The investigators believe that stereotactic body radiotherapy (SBRT) remains the only possible option to potentially treat VT. The investigators hypothesize that by administering SBRT at different dose levels and fractionation may achieve a better therapeutic ratio, defined as comparable efficacy with less risk of toxicity due to lower dose exposure to the normal tissue, including the heart vasculature, in patients when compared to VT patients who receive a dose of 25Gy in a single fraction which is the current treatment option.

This is a randomized dose de-escalation trial where the patients will be randomized in in one of the two experimental arms, receiving 1 single fraction OR 3 daily consecutive fractions of RT, and will be treated into a prespecified dose level group, based on the study development. The study includes three de-escalated consecutive dose level groups for each of two randomized treatment arms and there will be 3 patients per group and each group will receive a particular radiation treatment either as single treatments or three treatments.

The purpose of this treatment is to safely reduce episodes of VT.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Structural heart disease:

  1. Ischemic cardiomyopathy
  2. Non-ischemic cardiomyopathy
  3. Hypertrophic cardiomyopathy
* Refractory VT severity:

  1. VT leading to ICD shock with minimum 3 episodes in any 3-month period without reversible cause;
  2. Failed or intolerant to antiarrhythmic drug therapy (either amiodarone or ≥ 2 AADs) AND failed ablation (CA)
  3. OR ablation (CA) contraindicated
* Ability to understand study protocol and to write informed consent
* Willing to comply with specified pre-, post- and follow-up testing, evaluations and requirements
* Expected to remain available for at least 36 months after enrollment

Exclusion Criteria:

* Age \< 18 years
* Pregnancy
* Prior chest radiation therapy

Primary outcomes:
measure: Efficacy as measured by number of subjects with a reduction ≥ 60% (tracked by ICD recordings) ventricular tachycardia (VT) episodes
timeFrame: 6 months before treatment
measure: Efficacy as measured by number of subjects with a reduction ≥ 60% (tracked by ICD recordings) ventricular tachycardia (VT) episodes
timeFrame: 6 weeks post treatment
measure: Number of treatment-related serious adverse events (SAEs)
timeFrame: 6 weeks post treatment
Secondary outcomes:
measure: Number of ventricular tachycardia (VT) episodes
timeFrame: 3 months post
measure: Number of ventricular tachycardia (VT) episodes
timeFrame: 6 months post
measure: Number of ventricular tachycardia (VT) episodes
timeFrame: 12 months
measure: Number of subacute treatment side-effects
timeFrame: 3 months post
measure: Number of subacute treatment side-effects
timeFrame: 6 months post
measure: Number of late Adverse events
timeFrame: 1 year post
measure: Number of late Adverse events
timeFrame: 2 year post
measure: Overall survival
timeFrame: 1 year post
measure: Overall survival
timeFrame: 2 year post
measure: Recurrence free survival
timeFrame: 3 months post
measure: Recurrence free survival
timeFrame: 6 months post
measure: Recurrence free survival
timeFrame: 12 months post
measure: Recurrence free survival
timeFrame: 24 months post
measure: Number of incidents of implantable cardiac device (ICD) shock
timeFrame: 3 months before treatment
measure: Number of incidents of implantable cardiac device (ICD) shock
timeFrame: 3 months post treatment
measure: Number of Anti-Arrhythmic Drugs (AADs) administration
timeFrame: 3 months before treatment
measure: Number of Anti-Arrhythmic Drugs (AADs) administration
timeFrame: 3 months post treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Silvia Formenti, M.D.
role: PRINCIPAL_INVESTIGATOR
References: