Study to Evaluate VORTX Rx (Theresa)

Study Overview
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Brief Summary
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Multi-center, Open-labeled, Non-randomized Study to Evaluate the Acute Technical Performance and Safety Profile of the VORTX Rx® for Ablation of Primary and Metastatic Liver Tumors

Detailed Description
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The study will assess the technical performance of the VORTX Rx device to deliver acoustic energy for cavitation-based cellular destruction. The planned duration of a single target tumor will be 60 minutes or less in a single session and adjusted intra-procedurally as necessary per investigator discretion. Subjects in this study must have an adequate acoustic window in the abdominal space in order to be eligible for enrollment. All patients who undergo ablation with the investigation device will be treated in a hospital environment under general anesthesia not to exceed four hours.

Official Title
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Multi-center, Open-labeled, Non-randomized Study to Evaluate the Acute Technical Performance and Safety Profile of the VORTX Rx® for Ablation of Primary and Metastatic Liver Tumors (Theresa Study)

Conditions
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Carcinoma, Hepatocellular, Liver Metastases

Intervention / Treatment
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* Device: VORTX Rx treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent before any study procedure is performed. Subjects of both sexes aged 18 years or older. Patients diagnosed with liver cancer, including HCC or liver metastases from breast, pancreas and/or colorectal cancers. If biopsy is required, there will be a minimum of 2-week period after biopsy and before the ablation. HCC patients must meet the United Network for Organ Sharing and Organ Procurement and Transplantation Network (UNOS-OPTN) class 5 criteria for HCC (52). Liver metastases patients must meet minimum criteria of liver biopsy and/or tissue diagnosis of primary tumor or metastatic tumor with new or growing liver tumors radiologically consistent with metastases. Patients with liver cancer not candidates for surgical resection and/or not suitable for other locoregional treatments or patients who have not responded to or relapsed from conventional therapies. Previous treatment with chemotherapy and/or radiotherapy is permitted provided that these treatments have been discontinued more than 2 weeks before the ablation and whenever patients have recovered from any related toxicity (53). Previous treatment with immunotherapies is permitted provided that these therapies have been discontinued at least 4 weeks before the ablation and whenever patients have recovered from any related toxicity. Previous ablation/surgery on other tumors different from those that will be targeted with the VORTX Rx® is allowed whenever a minimum of 2 weeks has elapsed since the prior procedure(s). Tumor to be targeted for ablation will be clearly separated from other tumors or other critical areas (i.e. located in different segments of the liver) and located in segment 2, 3, 4, 5 or 6. Largest diameter of targeted tumor ≤3 cm. Tumor that will be targeted at a depth <10 cm from the skin surface. Must have an adequate acoustic window in the abdominal space to be able to visualize targeted tumor using ultrasound imaging; also must be able to visualize targeted tumor using MRI with optional CT imaging at investigator discretion. Patients who can undergo general anesthesia. Liver function score of Child-Pugh A or Child-Pugh B. ECOG PS 0, 1 or 2 at screening. Adequate liver function (ALT and AST < 2.5 x upper limit of normal [ULN]), renal function (serum creatinine <2 ULN and/or bilirubin <2.5 UNL) and hematologic function (neutrophil count > 1.0 x 109/L and platelet > 50 x 109/L). An INR <2 within the last 7 days prior to the ablation in patients receiving anticoagulants, and an INR <1.5 for patients not treated with anticoagulants. Platelets level >50 x 109/L within the last 7 days prior to the ablation. Exclusion Criteria: Patients who decline or are unable to understand, provide or are unwilling to sign an informed consent form. Pregnant or nursing (lactating) women; women of childbearing potential and sexually active that are unwilling to use adequate contraception (such as oral contraceptives, intrauterine contraceptive device or barrier method with spermicide or surgical sterilization). Targeted tumor not clearly separated (i.e. located in the same liver segment as another tumor). Targeted tumor located in liver segments 1, 7 or 8. Targeted tumor >3 cm. Tumor that will be targeted >10 cm from the skin surface. Tumor not clearly visible with diagnostic ultrasound and MRI. Liver function score of Child-Pugh C. Liver volume reserve <40% as measured by CT Scan (54). Major surgical procedure, biopsy or significant traumatic injury <2 weeks prior to the procedure or has not recovered from side effects/complications of such procedure or trauma. Patient who has not recovered to grade 1 or better from any AEs (except alopecia, fatigue, nausea, vomiting) related to previous anti neoplastic therapies. BMI >30. Parkinson's disease. History of bleeding disorders (e.g. von Willebrand disease) or patients suspected to have a bleeding disorder. Not able to temporarily discontinue warfarin, clopidogrel or any other long-acting anticoagulants at least two weeks before the procedure. Initiation of any anticancer treatment during the screening period and during the follow-up study visits. Life expectancy to be less than 6 months. Unable or unwilling to complete all required screening and/or follow-up assessments. Patients under ongoing treatment with an investigational medication or medical device that conflicts with the study device. Patients for whom the investigator considers that the ablation is not in the patient's best interest. Patients with active alcohol or drug addiction or any other condition that, in the investigator's opinion, would interfere with their ability to comply with the study requirements. Patients with any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol. Patients with known sensitivity to iodine.

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: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VORTX Rx treatment<br>Focused ultrasound ablation of liver tumors. | Device: VORTX Rx treatment<br>* Cavitation-based cellular destruction using focused ultrasound<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Technical Performance of the VORTX Rx® Medical Device for the Ablation of Primary and Metastatic Liver Tumors | Number of Lesions that were Successfully Ablated according to technical success definition established in the protocol. | 1-day post ablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile of the VORTX Rx. Incidence of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related | Number of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related | 2 months | 
| Local Tumor Progression | Number of patients who have indicated local tumor progression in at least one visit (1 week, 1 month, 2 months) for each tumor ablated. The ablation zone will be assessed post-procedurally to evaluate local tumor progression by contrast-enhanced MRI imaging | 1 week, 1 month and 2 months post-procedure. | 
| Involution of the Ablation Zone | The involution of the ablation zone will be assessed post-procedurally by contrast-enhanced MRI imaging at 24h, 1 week, 1 month and 2 months | 24hours, 1 week, 1 month and 2 months, post-procedure. | 
| Assessment of Liver panel_Part 1 | Liver panel will be evaluated on the basis of the change of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, gamma glutamyl transpeptidase (GGT) from baseline to evaluation visits 24 hours, 1 week and 1 and 2 months post procedure. | Screening, 24 hours, 1 week, 1 month and 2 months. | 
| Assessment of Liver Panel_Part 2 | Liver panel will be evaluated on the basis of the change of albumin from baseline to evaluation visits 24 hours, 1 week and 1 and 2 months post procedure. | 24 hours, 1 week and 1 month and 2 months | 
| Assessment of Liver Panel_Part 3 | Liver panel will be evaluated on the basis of the change of bilirubin from baseline to evaluation visits 24 hours, 1 week and 1 and 2 months post procedure | 24 hours, 1 week and 1month and 2 months | 
| Assessment of Liver Panel_part 4 | Liver panel will be evaluated on the basis of the change of prothrombin time (PT) from baseline to evaluation visits 24 hours, 1 week and 1 and 2 months post procedure | 24 hours, 1 week and 1month and 2 months | 
| Assessment of Liver Panel_Part 5 | Liver panel will be evaluated on the basis of the change of International normalized ratio (INR = A system established by the World Health Organization (WHO) and the International Committee on Thrombosis and Hemostasis for reporting the results of blood coagulation (clotting) tests) from baseline to evaluation visits 24 hours, 1 week and 1 and 2 months post procedure. The INR is derived from prothrombin time (PT) which is calculated as a ratio of the patient's PT to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the following formula: INR = Patient PT ÷ Control PT. Normal values for INR: 0.9-1.3. | 24 hours, 1 week and 1 month and 2 months | 
| Immunologic Assessment_Part 1 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments (including, but not limited to, immune tests: CD3+, CD4+, CD8+, CD45+, CD16+, CD56+ and CD19+ from Baseline/Screening to 1-day post ablation, 1 week and 1 and 2 months post procedureprocedure. | Baseline/Screening, 1-day post ablation, 1 week and 1 and 2 months post procedure | 
| Immunologic Assessment_Part 2 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments: C-reactive protein [CRP], from baseline to evaluation visits 1 day, 1 week and 1 and 2 months post procedure. | Screening, 24 hours, 1 week and 1 and 2 months post procedure. | 
| Immunologic Assessment_Part 3 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments (including, but not limited to, immune tests): complement C3 and C4, immunoglobulins [IgG, IgM, IgA] from baseline to evaluation visits 1 day, 1 week and 1 and 2 months post procedure. | Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure. | 
| Immunologic Assessment_Part 4 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments (including, but not limited to, immune tests: complement CH50, alfa-fetoprotein [AFP], Cancer Antigens CA15-3 [Breast Cancer] and CA 19-9 [Pancreatic Cancer]) from baseline to evaluation visits 1 day, 1 week and 1 and 2 months post procedure. | Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure. | 
| Immunologic Assessment_Part 5 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments (including, but not limited to, immune tests): interleukin-6 [IL-6] from baseline to evaluation visits 1 day, 1 week and 1 and 2 months post procedure. | Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure. | 
| Immunologic Assessment_Part 6 | Immunological response of ablation will be evaluated on the basis of immune tests conducted and tumor biomarker assessments (including, but not limited to, immune tests): carcinoembryonic antigen [CEA] from baseline to evaluation visits 1 day, 1 week and 1 and 2 months post procedure. | Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure. | 
| Assesment of Quality of Life by Using Patient Questtionaires EORTC QLQ-C30. (European Organization for Research and Treatment of Cancer) | The EORTC QLQ-C30 is a 30-item generic health-related QoL instrument designed to assess cancer patients' physical, psychological and social functioning. It is composed of 9 multi-item scales (5 functional scales [physical, role, cognitive, emotional, and social], a global QoL scale [GQoL], and 3 symptom scales [fatigue, pain, and nausea and vomiting]), 5 single-item symptom scales assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhea), and an item on the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0-100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/QoL represents a high QoL. However, a high score for a symptom scale/item represents a high level of symptomatology/problems. | Screening, 1 and 2 months post procedure. | 
| Pain Assessment by VAS Scale | Perform pain assessment by a 100 mm visual analog scale (VAS) where 0 is no pain and 100 is the maximum pain possible at 1-day and 1-week post-procedure. | 1-day post ablation and 1 week post procedure. | 
| Analgesic Requirements After the Ablation Procedure | Evaluate analgesic treatment prescription in the 24-hour period post-procedure and during the one week period post-procedure. | in the 24-hour period post-procedure and during the one week period post-procedure |