Study to Evaluate VORTX Rx (Theresa)

• Sponsor: HistoSonics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03741088
• Collaborator: (none)
• Enrollment: 8
• Locations: 3
• Arm: 1
• Actual Duration (Months): 15.9
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular; Liver Metastases	Device: VORTX Rx treatment	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Device Feasibility
• Official Title: 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)
• Actual Study Start Date: Mar 21, 2018
• Actual Primary Completion Date: May 15, 2019
• Actual Study Completion Date: Jul 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VORTX Rx treatment Focused ultrasound ablation of liver tumors.	Device: VORTX Rx treatment; Cavitation-based cellular destruction using focused ultrasound

Outcome Measures

Primary Outcome Measures

1. Acute Technical Performance of the VORTX Rx® Medical Device for the Ablation of Primary and Metastatic Liver Tumors [1-day post ablation]

   Number of Lesions that were Successfully Ablated according to technical success definition established in the protocol.

Secondary Outcome Measures

1. Safety Profile of the VORTX Rx. Incidence of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related [2 months]

   Number of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related

2. Local Tumor Progression [1 week, 1 month and 2 months post-procedure.]

   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

3. Involution of the Ablation Zone [24hours, 1 week, 1 month and 2 months, post-procedure.]

   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

4. Assessment of Liver panel_Part 1 [Screening, 24 hours, 1 week, 1 month and 2 months.]

   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.

5. Assessment of Liver Panel_Part 2 [24 hours, 1 week and 1 month and 2 months]

   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.

6. Assessment of Liver Panel_Part 3 [24 hours, 1 week and 1month and 2 months]

   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

7. Assessment of Liver Panel_part 4 [24 hours, 1 week and 1month and 2 months]

   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

8. Assessment of Liver Panel_Part 5 [24 hours, 1 week and 1 month and 2 months]

   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.

9. Immunologic Assessment_Part 1 [Baseline/Screening, 1-day post ablation, 1 week and 1 and 2 months post procedure]

   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.

10. Immunologic Assessment_Part 2 [Screening, 24 hours, 1 week and 1 and 2 months post procedure.]

    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.

11. Immunologic Assessment_Part 3 [Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.]

    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.

12. Immunologic Assessment_Part 4 [Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.]

    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.

13. Immunologic Assessment_Part 5 [Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.]

    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.

14. Immunologic Assessment_Part 6 [Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.]

    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.

15. Assesment of Quality of Life by Using Patient Questtionaires EORTC QLQ-C30. (European Organization for Research and Treatment of Cancer) [Screening, 1 and 2 months post procedure.]

    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.

16. Pain Assessment by VAS Scale [1-day post ablation and 1 week post procedure.]

    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.

17. Analgesic Requirements After the Ablation Procedure [in the 24-hour period post-procedure and during the one week period post-procedure]

    Evaluate analgesic treatment prescription in the 24-hour period post-procedure and during the one week period post-procedure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinica Diagonal	Esplugues De Llobregat	Barcelona	Spain	08950
2	Hospital universitario Mutua Terrassa	Terrassa	Barcelona	Spain	08221
3	Hospital Universitario Vall d´Hebrón	Barcelona		Spain	08035

Sponsors and Collaborators

• HistoSonics, Inc.

Investigators

• Principal Investigator: Joan Vidal Jove, MD, Mutua Terrassa , Barcelona, Spain

Study Documents (Full-Text)

• Study Protocol - Sep 26, 2018
• Statistical Analysis Plan - Jan 1, 2020
• Informed Consent Form - Sep 26, 2018

More Information

Publications

None provided.

• Responsible Party: HistoSonics, Inc.
• ClinicalTrials.gov Identifier: NCT03741088
• Other Study ID Numbers: 03.CP.0.3
• First Posted: Nov 14, 2018
• Last Update Posted: Apr 20, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Period Title: Overall Study
STARTED	8
COMPLETED	5
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 62.5%
>=65 years	3 37.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (13.6)
Sex: Female, Male (Count of Participants)
Female	5 62.5%
Male	3 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Spain	8 100%
Type of live tumors (Count of Participants)
Hepatocellular carcinoma	1 12.5%
Liver metastasis	7 87.5%
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	25.1
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
ECOG 0	2 25%
ECOG 1	6 75%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	8
Measure lesions	11
Count of Units [lesions]	11

2. Secondary Outcome

Title	Safety Profile of the VORTX Rx. Incidence of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related
Description	Number of Adverse Events (Serious and Non-serious) That Are Probably or Definitely Device-related
Time Frame	2 months

Outcome Measure Data

Analysis Population Description

Although only 5 participants performed all protocol visits, adverse events from all patients were reported and analyzed. Any of the 55 AEs reported was device-related.

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	8
Measure Adverse Events	55
Number [Adverse Events]	0

3. Secondary Outcome

Title	Local Tumor Progression
Description	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
Time Frame	1 week, 1 month and 2 months post-procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	8
Progression: YES	2 25%
Progression: NO	5 62.5%
Progression: No data	1 12.5%

4. Secondary Outcome

Title	Involution of the Ablation Zone
Description	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
Time Frame	24hours, 1 week, 1 month and 2 months, post-procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	5
Measure lesions	6
Ablation zone volume (cm3): 24 hours	10.5500 (6.34405)
Ablation zone volume (cm3): 1 week	8.5000 (9.56682)
Ablation zone volume (cm3): 1 month	5.9383 (10.02174)
Ablation zone volume (cm3): 2 months	4.7683 (9.47795)

5. Secondary Outcome

Title	Assessment of Liver panel_Part 1
Description	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.
Time Frame	Screening, 24 hours, 1 week, 1 month and 2 months.

Outcome Measure Data

Analysis Population Description

Only 4 patients have these parameters determined in all study points (screening, 24h, 1 day, 1 month and 2 months post-ablation)

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
AST Screening	60.7500 (33.83662)
AST 24 hours	183.5000 (80.71555)
AST 1 week	47.0000 (25.17936)
AST 1 month	40.7500 (10.68878)
AST 2 months	40.5000 (19.94158)
ALT Screening	44.0000 (22.13594)
ALT 24 hours	139.0000 (56.12486)
ALT 1 week	58.5000 (30.27100)
ALT 1 month	27.5000 (12.60952)
ALT 2 months	30.0000 (15.55635)
GGT Screening	127.2500 (105.05673)
GGT 24 hours	118.0000 (111.48692)
GGT 1 week	159.7500 (176.57364)
GGT 1 month	162.5000 (139.50986)
GGT 2 months	102.5000 (43.23964)
Alkaline Phosphatase Screening	156.5000 (139.89639)
Alkaline Phosphatase 24 hours	127.2500 (67.14847)
Alkaline Phosphatase 1 week	165.0000 (88.67168)
Alkaline Phosphatase 1 month	146.7500 (66.33941)
Alkaline Phosphatase 2 months	130.2500 (74.44629)

6. Secondary Outcome

Title	Assessment of Liver Panel_Part 2
Description	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.
Time Frame	24 hours, 1 week and 1 month and 2 months

Outcome Measure Data

Analysis Population Description

Only 4 patients have these parameters determined in all study points (screening, 24h, 1 day, 1 month and 2 months post-ablation)

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Albumin Screening	40.0250 (2.88603)
Albumin 24 hours	34.7500 (1.13284)
Albumin 1 week	37.5250 (1.95683)
Albumin 1 month	39.3750 (0.63966)
Albumin 2 months	40.1750 (1.65806)

7. Secondary Outcome

Title	Assessment of Liver Panel_Part 3
Description	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
Time Frame	24 hours, 1 week and 1month and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Total Bilirrubin Screening	0.7525 (0.42578)
Total Bilirrubin 24 hours	0.6425 (0.20549)
Total Bilirrubin 1 week	0.7600 (0.32934)
Total Bilirrubin 1 month	0.5250 (0.11561)
Total Bilirrubin 2 months	0.7050 (0.31268)

8. Secondary Outcome

Title	Assessment of Liver Panel_part 4
Description	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
Time Frame	24 hours, 1 week and 1month and 2 months

Outcome Measure Data

Analysis Population Description

Only 4 patients have these parameters determined in all study points (screening, 24h, 1 day, 1 month and 2 months post-ablation)

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Prothrombin time Screening	95.2500 (5.50000)
Prothrombin time 24 hours	92.5000 (9.94987)
Prothrombin time 1 week	92.7500 (8.38153)
Prothrombin time 1 month	98.7500 (2.50000)
Prothrombin time 2 months	91.2500 (17.50000)

9. Secondary Outcome

Title	Assessment of Liver Panel_Part 5
Description	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.
Time Frame	24 hours, 1 week and 1 month and 2 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
INR Screening	1.0500 (0.5774)
INR 24 hours	1.0750 (0.09574)
INR 1 week	1.0500 (0.05774)
INR 1 month	1.0250 (0.05000)
INR 2 months	1.0750 (0.15000)

10. Secondary Outcome

Title	Immunologic Assessment_Part 1
Description	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.
Time Frame	Baseline/Screening, 1-day post ablation, 1 week and 1 and 2 months post procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
CD3+ (T cells) Screening	801.7500 (374.33708)
CD3+ (T cells) 24 hours	618.2500 (365.48814)
CD3+ (T cells) 1 week	713.7500 (234.09596)
CD3+ (T cells) 1 month	587.7500 (253.11575)
CD3+ (T cells) 2 months	632.0000 (150.53017)
CD4+ (T helper cells) Screening	469.2500 (146.20619)
CD4+ (T helper cells) 24 hours	374.7500 (128.99709)
CD4+ (T helper cells) 1 week	445.2500 (121.94637)
CD4+ (T helper cells) 1 month	357.0000 (159.34240)
CD4+ (T helper cells) 2 months	382.2500 (77.24150)
CD8+ (T suppressor/cytotoxic cells) Screening	262.7500 (223.82638)
CD8+ (T suppressor/cytotoxic cells) 24 hours	220.5000 (204.31593)
CD8+ (T suppressor/cytotoxic cells) 1 week	230.5000 (139.01679)
CD8+ (T suppressor/cytotoxic cells) 1 month	186.7500 (136.19196)
CD8+ (T suppressor/cytotoxic cells) 2 months	177.2500 (85.47660)
CD45+ (leucocyte common antigen) Screening	1054.1425 (384.46746)
CD45+ (leucocyte common antigen) 24 hours	843.0350 (349.94733)
CD45+ (leucocyte common antigen) 1 week	938.3700 (251.60549)
CD45+ (leucocyte common antigen) 1 month	788.4275 (257.71702)
CD45+ (leucocyte common antigen) 2 months	831.2675 (194.76464)
CD16+ Screening	134.3000 (69.78811)
CD16+ 24 hours	78.4750 (50.40353)
CD16+ 1 week	116.1750 (65.72460)
CD16+ 1 month	109.7500 (53.11230)
CD16+ 2 months	100.5000 (47.59202)
CD56+ (NKT cells) Screening	85.4500 (85.14507)
CD56+ (NKT cells) 24 hours	56.5000 (61.00213)
CD56+ (NKT cells) 1 week	73.9500 (69.58934)
CD56+ (NKT cells) 1 month	63.2500 (68.07533)
CD56+ (NKT cells) 2 months	60.7500 (50.12900)
CD19+ (B-lymphocyte antigen) Screening	85.0000 (58.66856)
CD19+ (B-lymphocyte antigen) 24 hours	83.5000 (58.31238)
CD19+ (B-lymphocyte antigen) 1 week	86.5000 (53.10053)
CD19+ (B-lymphocyte antigen) 1 month	70.0000 (50.51732)
CD19+ (B-lymphocyte antigen) 2 months	87.0000 (51.71718)

11. Secondary Outcome

Title	Immunologic Assessment_Part 2
Description	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.
Time Frame	Screening, 24 hours, 1 week and 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
C reactive protein Screening	5.9750 (5.67355)
C reactive protein 24 hours	6.0250 (7.06323)
C reactive protein 1 week	30.8250 (53.05735)
C reactive protein 1 month	4.7750 (3.57713)
C reactive protein 2 months	11.9500 (8.85795)

12. Secondary Outcome

Title	Immunologic Assessment_Part 3
Description	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.
Time Frame	Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Complement C3 Screening	144.0000 (53.61592)
Complement C3 24 hours	123.2000 (25.76354)
Complement C3 1 week	150.5000 (22.75229)
Complement C3 1 month	143.9000 (44.60239)
Complement C3 2 months	134.7500 (26.88711)
Complement C4 Screening	30.7750 (20.29949)
Complement C4 24 hours	23.7750 (6.58401)
Complement C4 1 week	29.8250 (9.00717)
Complement C4 1 month	26.9500 (11.01348)
Complement C4 2 months	28.0750 (14.47236)
IgG Screening	867.2500 (326.38359)
IgG 24 hours	792.9000 (354.83048)
IgG 1 week	856.0000 (335.22430)
IgG 1 month	916.7500 (338.63784)
IgG 2 months	899.0000 (334.19655)
IgM Screening	132.6250 (59.75139)
IgM 24 hours	120.9000 (51.44745)
IgM 1 week	132.3500 (45.62846)
IgM 1 month	140.7500 (43.69115)
IgM 2 months	141.2500 (52.94075)
IgA Screening	147.5000 (133.49871)
IgA 24 hours	130.0000 (119.05766)
IgA 1 week	142.8000 (131.15955)
IgA 1 month	145.9500 (116.11530)
IgA 2 months	129.3750 (84.51147)

13. Secondary Outcome

Title	Immunologic Assessment_Part 4
Description	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.
Time Frame	Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Complement CH50 Screening	72.7500 (26.87471)
Complement CH50 24 hours	61.5000 (37.59876)
Complement CH50 1 week	61.0000 (34.02940)
Complement CH50 1 month	52.2500 (24.18505)
Complement CH50 2 months	60.2500 (36.59121)
AFP Screening	544.8050 (1084.79682)
AFP 24 hours	417.8550 (831.43014)
AFP 1 week	502.2350 (999.84372)
AFP 1 month	264.1675 (523.22173)
AFP 2 months	224.5900 (441.61247)
CA 15-3 (breast cancer) Screening	15.8500 (9.02940)
CA 15-3 (breast cancer) 24 hours	14.0000 (6.66433)
CA 15-3 (breast cancer) 1 week	14.3750 (7.20804)
CA 15-3 (breast cancer) 1 month	16.2250 (9.31786)
CA 15-3 (breast cancer) 2months	15.4250 (7.08396)
CA 19-9 (pancreatic cancer) Screening	167.8175 (300.24702)
CA 19-9 (pancreatic cancer) 24 hours	174.8450 (312.86710)
CA 19-9 (pancreatic cancer) 1 week	169.1675 (290.56204)
CA 19-9 (pancreatic cancer) 1 month	168.1200 (285.77017)
CA 19-9 (pancreatic cancer) 2 months	256.9525 (475.14915)

14. Secondary Outcome

Title	Immunologic Assessment_Part 5
Description	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.
Time Frame	Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Interleukin-6 Screening	4.2225 (2.88648)
Interleukin-6 24 hours	3.4575 (1.97481)
Interleukin-6 1 week	14.7850 (14.05719)
Interleukin-6 1 month	3.8750 (2.37905)
Interleukin-6 2 months	5.8125 (2.84372)

15. Secondary Outcome

Title	Immunologic Assessment_Part 6
Description	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.
Time Frame	Screening, 24 hours post ablation, 1 week and 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
CEA Screening	46.9300 (50.75086)
CEA 24 hours	50.4200 (55.16530)
CEA 1 week	37.7925 (45.10227)
CEA 1 month	44.6150 (64.11322)
CEA 2 months	54.0225 (97.45371)

16. Secondary Outcome

Title	Assesment of Quality of Life by Using Patient Questtionaires EORTC QLQ-C30. (European Organization for Research and Treatment of Cancer)
Description	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.
Time Frame	Screening, 1 and 2 months post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	4
Measure ablation procedures	4
Global health status/QoL Screening	70.8333 (15.95712)
Global health status/QoL 1 month	58.3333 (28.05418)
Global health status/QoL 2 months	70.8333 (25.00000)
Physical functioning Screening	81.6667 (12.61980)
Physical functioning 1 month	83.3333 (13.87777)
Physical functioning 2 months	81.6667 (18.35857)
Role functioning screening	87.5000 (15.95712)
Role functioning 1 month	70.8333 (28.46375)
Role functioning 2 months	83.3333 (13.60828)
Emotional functioning Screening	87.5000 (8.33333)
Emotional functioning 1 month	87.5000 (19.83730)
Emotional functioning 2 months	83.3333 (18.00206)
Cognitive functioning Screening	79.1667 (20.97176)
Cognitive functioning 1 month	75.0000 (21.51657)
Cognitive functioning 2 months	79.1667 (31.54949)
Social functioning Screening	95.8333 (8.33333)
Social functioning 1 month	83.3333 (13.60828)
Social functioning 2 months	95.8333 (8.33333)
Fatigue Screening	30.5556 (13.98117)
Fatigue 1 month	41.6667 (27.77778)
Fatigue 2 months	25.0000 (24.63729)
Nausea and vomiting Screening	0 (0)
Nausea and vomiting 1 month	0 (0)
Nausea and vomiting 1 months	0 (0)
Pain Screening	16.6667 (23.57023)
Pain 1 month	20.8333 (31.54949)
Pain 2 months	41.6667 (34.69443)
Dyspnea Screening	0 (0)
Dyspnea 1 month	0 (0)
Dyspnea 2 months	0 (0)
Insomnia Screening	41.6667 (41.94352)
Insomnia 1 month	33.3333 (47.14045)
Insomnia 2 months	25.0000 (31.91424)
Appetite loss Screening	25.0000 (50.00000)
Appetite loss 1 month	50.0000 (43.03315)
Appetite loss 2 months	8.3333 (16.66667)
Constipation Screening	8.3333 (16.66667)
Constipation 1 month	0 (0)
Constipation 2 months	0 (0)
Diarrhea Screening	33.3333 (47.14045)
Diarrhea 1 month	16.6667 (19.24501)
Diarrhea 2 months	16.6667 (19.24501)
Financial difficulties Screening	16.6667 (19.24501)
Financial difficulties 1 month	8.3333 (16.66667)
Financial difficulties 2 months	8.3333 (16.66667)

17. Secondary Outcome

Title	Pain Assessment by VAS Scale
Description	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.
Time Frame	1-day post ablation and 1 week post procedure.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	7
Measure ablation procedures	7
VAS score: 24 hours	4.3 (7.9)
VAS score: 1 week	25.0 (18.9)

18. Secondary Outcome

Title	Analgesic Requirements After the Ablation Procedure
Description	Evaluate analgesic treatment prescription in the 24-hour period post-procedure and during the one week period post-procedure.
Time Frame	in the 24-hour period post-procedure and during the one week period post-procedure

Outcome Measure Data

Analysis Population Description

Number of patients with at least one drug due to Post-procedure pain (concomitant medication form).

Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
Measure Participants	8
At least one drug due to post-procedure pain: YES	5 62.5%
At least one drug due to post-procedure pain: NO	3 37.5%

Adverse Events

Time Frame	2 months
Arm/Group Title	VORTX Rx Treatment
Arm/Group Description	Focused ultrasound ablation of liver tumors. VORTX Rx treatment: Cavitation-based cellular destruction using focused ultrasound
All Cause Mortality
	VORTX Rx Treatment
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	VORTX Rx Treatment
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
General disorders
FEVER	1/8 (12.5%)	1
Metabolism and nutrition disorders
HYPOCALCEMIA	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	VORTX Rx Treatment
	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)
Gastrointestinal disorders
Constipation	2/8 (25%)
Gastrointestinal pain	1/8 (12.5%)
Nausea	2/8 (25%)
General disorders
Abdominal discomfort	1/8 (12.5%)
Abdominal pain	1/8 (12.5%)
Fatigue	4/8 (50%)
Fever	1/8 (12.5%)
General pain	1/8 (12.5%)
Occasional fever	1/8 (12.5%)
Hepatobiliary disorders
Transaminase elevation	1/8 (12.5%)
Alkaline phosphatase increase	1/8 (12.5%)
ALT increase	4/8 (50%)
Ascites	1/8 (12.5%)
AST increase	4/8 (50%)
GGT increase	2/8 (25%)
Jaundice	1/8 (12.5%)
Metabolism and nutrition disorders
Anemia	1/8 (12.5%)
Anorexia	2/8 (25%)
Appetite increase	1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Coccyx pain	1/8 (12.5%)
Left leg pain	1/8 (12.5%)
Malleolar edema with fovea	1/8 (12.5%)
Pain in right shoulder	1/8 (12.5%)
Pain in right side	1/8 (12.5%)
Nervous system disorders
Adverse reaction to analeptics and opioid receptor antagonists	1/8 (12.5%)
Lipotomy	1/8 (12.5%)
Sciatic pain	3/8 (37.5%)
Tingling in feet and hands	1/8 (12.5%)
Renal and urinary disorders
Choluria	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Chest punctures	1/8 (12.5%)
Right basal pneumonia	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Desquamative lesions	1/8 (12.5%)
Itchy skin	1/8 (12.5%)
Vascular disorders
Swollen ankles	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The results or conclusions of this study will be reported at scientific congresses and published in scientific journals. The investigator agrees to maintain this information in strict confidence, and will not use it for any other purpose without the written authorization of the sponsor.