Refractory Ventricular Tachycardia
Conditions
Brief summary
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.
Interventions
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.
Sponsors
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ICD (Implantable Cardioverter Defibrillator) Shock Free Survival | 6 months | ICD (implantable cardioverter defibrillator) shock free survival at six months |
| Incidence of Salvage Definitive Anti-arrhythmia Therapy (Cardiac Transplant) | 5 years | Incidence of salvage definitive anti-arrhythmia therapy (cardiac transplant) over 5 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Return of Ventricular Tachycardia Requiring Defibrillation, Intravenous Drug Therapy or Readmission to Hospital | 5 years | Incidence of return of ventricular tachycardia requiring defibrillation, intravenous drug therapy or readmission to hospital over 5 years |
| Incidence of ICD Shocks | 12 months post-SABR procedure | Incidence of ICD shocks 12 months post-SABR procedure |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Decline of LV Ejection Fraction by More Than 5% on Two Consecutive Echocardiograms | 5 years | Incidence of decline of LV ejection fraction by more than 5% on two consecutive echocardiograms over 5 years |
| Incidence of Persistent Increase in Baseline Supplemental Oxygen Requirement by 1L for a Duration of >3 Months | 5 years | Incidence of persistent increase in baseline supplemental oxygen requirement by 1L for a duration of \>3 months over 5 years |
| Incidence of Steroid Use for Radiotherapy Related Indications | 5 years | — |
| Overall Survival | Followed for 10 years + | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stereotactic Ablation Treatment Arm This is a single-arm, non-blinded study.
Stereotactic Ablative Radiotherapy (SABR): 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. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Stereotactic Ablation Treatment Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
ICD (Implantable Cardioverter Defibrillator) Shock Free Survival
ICD (implantable cardioverter defibrillator) shock free survival at six months
Time frame: 6 months
Population: Patients with refractory VT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Ablation Treatment Arm | ICD (Implantable Cardioverter Defibrillator) Shock Free Survival | 1 Participants |
Primary
Incidence of Salvage Definitive Anti-arrhythmia Therapy (Cardiac Transplant)
Incidence of salvage definitive anti-arrhythmia therapy (cardiac transplant) over 5 years.
Time frame: 5 years
Population: Single participant was lost to followup prior to 5-year assessment
Secondary
Incidence of ICD Shocks
Incidence of ICD shocks 12 months post-SABR procedure
Time frame: 12 months post-SABR procedure
Population: Subject was followed for 28 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stereotactic Ablation Treatment Arm | Incidence of ICD Shocks | 1 Participants |
Secondary
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
Time frame: 5 years
Population: Study participant was lost to follow-up prior to 5-year assessment
Other Pre-specified
Incidence of Decline of LV Ejection Fraction by More Than 5% on Two Consecutive Echocardiograms
Incidence of decline of LV ejection fraction by more than 5% on two consecutive echocardiograms over 5 years
Time frame: 5 years
Population: Subject was not followed for 5 years
Other Pre-specified
Incidence of Persistent Increase in Baseline Supplemental Oxygen Requirement by 1L for a Duration of >3 Months
Incidence of persistent increase in baseline supplemental oxygen requirement by 1L for a duration of \>3 months over 5 years
Time frame: 5 years
Population: Subject was not followed for 5 years
Other Pre-specified
Incidence of Steroid Use for Radiotherapy Related Indications
Time frame: 5 years
Population: Subject was not followed for 5 years
Other Pre-specified
Overall Survival
Time frame: Followed for 10 years +
Population: Subject was not followed for 10 years