Hepatocellular Carcinoma, Liver Metastases, Liver Neoplasms
Conditions
Brief summary
This trial is a single arm, non-randomized prospective trial. The objective of this trial is to evaluate the efficacy and safety of the HistoSonics System for the treatment of primary or metastatic tumors located in the liver. The co-primary safety and efficacy endpoints must be met for the trial to be successful.
Detailed description
This trial is a single arm, non-randomized, multicenter, prospective trial. Following histotripsy treatment of liver tumor(s), subjects will undergo imaging ≤36 hours post-index procedure to determine technical success. Subjects will then be followed for 30 days. Additionally, subjects will be evaluated at 6 months and followed annually for up to five (5) years post-index procedure. The #HOPE4LIVER US trial required pooling data from #HOPE4LIVER US and #HOPE4LIVER EU/UK (NCT04573881). Subjects were treated with the same intervention (HistoSonics System) using identical protocols tailored to the regulatory requirements for each geography.
Interventions
DEVICEHistoSonics System
The HistoSonics System (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound.
Sponsors
HistoSonics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single arm, non-randomized prospective trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is ≥18 years of age 2. Subject has signed the Ethics Committee (EC) or Institutional Review Board (IRB) approved trial Informed Consent Form (ICF) prior to any trial related tests/procedures and is willing to comply with trial procedures and required follow-up assessments 3. Subject is diagnosed with hepatocellular carcinoma (HCC) or liver metastases (mets) from other primary cancers 4. Subject is able to undergo general anesthesia 5. Subject has a Child-Pugh Score of A or B 6. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 0-2 at baseline screening 7. Subject meets the following functional criteria, ≤7 days prior to the index-procedure: * Liver function: Alanine transaminase (ALT) and Aspartate transaminase (AST) \<2.5x upper limit of normal (ULN) and/or bilirubin \<2.5 ULN, and * Renal function: serum creatinine \<2x ULN, and * Hematologic function: neutrophil count \>1.0 x 10\^9/L and platelet \>50 x 10\^9/L 8. Subject has an International Normalized Ratio (INR) score of \<2.0 , ≤7 days prior to the index procedure 9. Subject has not responded to and/or has relapsed and/or is intolerant of other available therapies including locoregional therapies, chemotherapy, immunotherapy and targeted therapies 10. The tumor(s) selected for histotripsy treatment must be ≤3 cm in longest diameter 11. Subject has an adequate acoustic window to visualize targeted tumor(s) using ultrasound imaging 12. Subject has a maximum of three (3) tumors to be treated with histotripsy during the index procedure, regardless of how many tumors the subject has.
Exclusion criteria
1. Subject is pregnant or planning to become pregnant or nursing (lactating) during the trial period 2. Subject is enrolled in another investigational trial and/or is taking investigational medication and/or has been treated with an investigational device ≤30-days prior to planned index procedure date 3. In the Investigator's opinion, the subject has co-morbid disease(s) or condition(s) that would cause undue risk and preclude safe use of the HistoSonics System 4. Subject has a serum creatinine \>2.0 mg/dL or estimated glomerular filtration rate (EGFR) \<30, unless on dialysis 5. Subject has major surgical procedure or significant traumatic injury ≤2 weeks prior to the planned index procedure or not fully recovered (CTCAE grade 1 or better) from side effects/complications of such procedure or trauma 6. Subject has not recovered to common terminology criteria for adverse events (CTCAE) grade 1 or better from any adverse effects (except alopecia, fatigue, nausea, vomiting and peripheral neuropathy) related to previous anti-cancer therapy 7. Subject has a history of, or suspected to have, bleeding disorders that are uncorrectable 8. Subject has coagulopathy that is uncorrectable 9. Subject has a planned cancer treatment (e.g. resection, chemotherapy, etc.) after the planned index-procedure date and prior to completion of the 30-day follow-up visit 10. Subject has previous treatment with bevacizumab that has not been discontinued \>40 days prior to the planned index-procedure date 11. Subject has planned bevacizumab treatment prior to completion of the 30-day follow-up visit 12. Subject has previous treatments with chemotherapy and/or radiotherapy that has not been discontinued ≥2 weeks prior to the planned index-procedure date and has not recovered (CTCAE grade 1 or better) from related toxicity (except alopecia and peripheral neuropathy) 13. Subject has previous treatment with immunotherapies that has not been discontinued ≥4 weeks prior to the index-procedure and has not recovered from related toxicity (CTCAE grade 1 or better) 14. Subject has a life expectancy less than six (\<6) months 15. In the opinion of the Investigator, histotripsy is not a treatment option for the subject 16. Subject has a concurrent condition that, in the investigator's opinion, could jeopardize the safety of the subject or compliance with the protocol 17. Subjects' tumor(s) is not treatable by the System's working ranges (refer to User Manual) 18. Subject has a known sensitivity to contrast media and cannot be adequately pre-medicated 19. Subjects' target tumor(s) has/have had prior locoregional therapy (e.g. ablation, embolization, radiation) 20. Subject is eligible for surgical resection 21. Targeted tumor(s) treatment volume overlaps a non-targeted tumor visible via imaging 22. The targeted tumor(s) is not clearly visible with diagnostic ultrasound and computed tomography (CT) or magnetic resonance (MR) imaging 23. The targeted tumor(s) is located in liver segment 1 24. The Planned Treatment Volume intended to cover the targeted tumor includes or encompasses any portion of the main portal vein, common hepatic duct, common bile duct, gallbladder or stomach/bowel.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy: Technical Success | ≤36 hours post-index procedure | Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. \[Core Laboratory Adjudicated\] Primary efficacy was assessed per tumor with a performance goal of greater than 70%. Primary efficacy was assessed after the first forty (40) consecutive evaluable subjects were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success. |
| Primary Safety: Procedure-Related Major Complications | 30 days post-index procedure | Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. \[Clinical Events Committee Adjudicated\] Primary safety was assessed per participant with a performance goal of less than 25%. Primary safety was assessed on all subjects enrolled, after the first forty (40) consecutive subjects evaluable for technical success were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success. Enrollment of 44 total subjects was required to assess forty (40) subjects evaluable for technical success. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Technical Success | ≤36 hours post-index procedure | Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. \[Core Laboratory Adjudicated\] |
| Procedure-Related Major Complications | 30 days post-index procedure | Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. \[Clinical Events Committee Adjudicated\] |
| Secondary Efficacy: Technique Efficacy | 30 days post-index procedure | Technique efficacy, defined as the lack of a nodular or mass-like area of enhancement within or along the edge of the treatment volume assessed via CT or MR imaging at 30-days post-procedure. \[Core Laboratory Adjudicated\] |
| Secondary Safety: All Adverse Events | 30 days post-index procedure | Number of adverse events (serious and non-serious) reported within 30 days post-index procedure. \[Clinical Events Committee Adjudicated\] |
Countries
United States
Participant flow
Recruitment details
As the #HOPE4LIVER EU/UK and #HOPE4LIVER US trials were developed with an identical study design using the same device, the data from all 47 participants enrolled were pooled for analysis. The pooled data contains 23 participants treated in the US and 24 participants treated in Europe. Data from the first 44/47 participants enrolled were analyzed for primary effectiveness and primary safety. Follow-up beyond 30 days is ongoing.
Participants by arm
| Arm | Count |
|---|---|
| HistoSonics System HistoSonics System: The HistoSonics System (System) is intended for the destruction of liver tissue using histotripsy, a non-thermal, mechanical process using focused ultrasound. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Participant in active follow-up at 30 days | 47 |
Baseline characteristics
| Characteristic | HistoSonics System |
|---|---|
| Age, Continuous | 63.0 years STANDARD_DEVIATION 12.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 45 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 24 Participants |
| Type of tumor Hepatocellular carcinoma | 19 Participants |
| Type of tumor Liver metastasis | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 47 |
| other Total, other adverse events | 35 / 47 |
| serious Total, serious adverse events | 9 / 47 |
Outcome results
Primary
Primary Efficacy: Technical Success
Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. \[Core Laboratory Adjudicated\] Primary efficacy was assessed per tumor with a performance goal of greater than 70%. Primary efficacy was assessed after the first forty (40) consecutive evaluable subjects were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success.
Time frame: ≤36 hours post-index procedure
Population: Primary efficacy was assessed after the first forty (40) consecutive evaluable subjects were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Primary Efficacy: Technical Success | 95.5 percentage of tumors |
95% CI: [83.72, 100]
Primary
Primary Safety: Procedure-Related Major Complications
Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. \[Clinical Events Committee Adjudicated\] Primary safety was assessed per participant with a performance goal of less than 25%. Primary safety was assessed on all subjects enrolled, after the first forty (40) consecutive subjects evaluable for technical success were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success. Enrollment of 44 total subjects was required to assess forty (40) subjects evaluable for technical success.
Time frame: 30 days post-index procedure
Population: Primary safety was assessed on all subjects enrolled, after the first forty (40) consecutive subjects evaluable for technical success were enrolled. Evaluable subjects had sufficient CT or MR imaging data to allow the independent core laboratory to evaluate technical success. Enrollment of 44 total subjects was required to assess forty (40) subjects evaluable for technical success.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Primary Safety: Procedure-Related Major Complications | 6.8 percentage of participants |
95% CI: [2.35, 18.23]
Secondary
Procedure-Related Major Complications
Number of index procedure related major complications, including device-related events defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher toxicities observed up to 30-days post index-procedure. \[Clinical Events Committee Adjudicated\]
Time frame: 30 days post-index procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Procedure-Related Major Complications | 6.4 percentage of participants |
Secondary
Secondary Efficacy: Technique Efficacy
Technique efficacy, defined as the lack of a nodular or mass-like area of enhancement within or along the edge of the treatment volume assessed via CT or MR imaging at 30-days post-procedure. \[Core Laboratory Adjudicated\]
Time frame: 30 days post-index procedure
Population: Six of the 47 tumors analyzed for technical success had missing or insufficient imaging data for the core laboratory to evaluate technique efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Secondary Efficacy: Technique Efficacy | 82.9 percentage of tumors |
Secondary
Secondary Safety: All Adverse Events
Number of adverse events (serious and non-serious) reported within 30 days post-index procedure. \[Clinical Events Committee Adjudicated\]
Time frame: 30 days post-index procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Secondary Safety: All Adverse Events | 108 adverse events |
Secondary
Technical Success
Technical success, defined as the treatment volume/treatment dimensions being greater than or equal to the targeted tumor, and with complete tumor coverage, via computed tomography (CT) or magnetic resonance (MR) imaging. \[Core Laboratory Adjudicated\]
Time frame: ≤36 hours post-index procedure
Population: Five tumors had insufficient imaging data for the core laboratory to evaluate technical success.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HistoSonics System | Technical Success | 95.7 percentage of tumors |