The HistoSonics Investigational System for Treatment of Primary Solid Renal Tumors Using Histotripsy
Phase: NA
Conditions: Renal Cancer, Tumor, Solid, Kidney Cancer, Tumor, Tumor, Benign, Kidney Neoplasms
Sponsor: HistoSonics, Inc.

 
CAIN Protocol Synopsis 
NCT05432232 
 
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Oﬃcial Title: The HistoSonics Investigational System for treatment of primary solid renal tumors 
using histotripsy (CAIN) 
NCT Number: NCT05432232 
Protocol Date: November 22, 2023 (CSP2276 Revision E) 
 
 

 
CAIN Protocol Synopsis 
NCT05432232 
 
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Title 
The HistoSonics Investigational System for treatment of primary solid renal tumors using 
histotripsy (CAIN) 
Clinical Investigation 
Protocol Identification 
Code 
CAIN Sponsor Clinical Study Number: CSP2276 Revision E (22Nov2023) 
ClinicalTrials.gov Identifier: NCT05432232 
Trial Purpose 
The purpose of this trial is to evaluate the technical success and safety profile of the 
HistoSonics Investigational System for the treatment of primary solid renal tumors. 
Trial Design  
This trial is a prospective, multi-center, single-arm pilot trial designed to evaluate the 
effectiveness and safety profile of the HistoSonics Investigational System in treating 
primary solid renal tumors. Following histotripsy treatment of the solid renal tumor, 
subjects will undergo imaging ≤36 hours post-index procedure to determine technical 
success. Additionally, subjects will be followed 180 days (6 months) post-index 
procedure, with evaluations at the 14-day, 30-day, 90-day, and 180-day time points to 
establish the efficacy and safety profile of the HistoSonics Investigational System. 
Trial Population 
Subjects who are 18 years of age or older with a diagnosis of a solid renal tumor. 
Objective 
The objective of this trial is to generate data to support a pivotal trial for the HistoSonics 
Investigational System for use in the kidney. 
Device Name  
HistoSonics Investigational System (System) 
Indication Under 
Investigation 
The indication under investigation is use of the HistoSonics Investigational System for 
the non-invasive destruction of kidney tissue using histotripsy, a non-thermal 
mechanical process of focused ultrasound. 
Enrollment 
Up to twenty (20) combined male and female subjects treated at up to four (4) clinical 
sites located in Europe and/or United Kingdom. 
Duration of Trial 
The duration of this trial is expected to be approximately eighteen (18) months. 
Primary Endpoints 
Primary Effectiveness Endpoint: 
Technical success defined as complete coverage of the tumor as determined ≤36 hours 
post-index procedure by magnetic resonance imaging (MRI) or computerized 
tomography (CT). [Core Lab Adjudicated] 
Primary Safety Endpoint: 
Freedom from index procedure related major complications, defined by Clavien-Dindo 
Classification Grade 3 or higher up to 30 days after the last histotripsy procedure. 
[Clinical Events Committee Adjudicated] 
Secondary Endpoints 
1. Technique efficacy (primary) defined as the percentage of targeted tumors 
successfully eradicated post-index procedure assessed via MRI or CT at 90-days 
post-index procedure without repeat Histotripsy [Core Lab Adjudicated] 
2. Technique efficacy (secondary) defined as the percentage of targeted tumors 
successfully eradicated post-index procedure assessed via MRI or CT at 90-days 
post-index procedure after repeat Histotripsy [Core Lab Adjudicated] 
Follow-Up Visits 
All treated subjects will have a 14-day, 30-day, 90-day, and 180-day follow up 
assessment or until the trial is closed, whichever comes first. 
General Inclusion 
 
Subjects are eligible for the trial if all the following criteria are met: 

 
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1. Subject is ≥18 years of age.  
2. Subject has signed the Ethics Committee (EC) 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 a non-metastatic solid renal mass ≤3cm confirmed via CT 
or MRI ≤ 30 days prior to the index procedure date. 
4. Subject can tolerate general anesthesia. 
5. Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 
grade 0-2 at baseline screening.  
6. Subject meets all the following functional criteria at ≤14 days prior to the planned 
index procedure date:     
• 
White Blood Cell (WBC) ≥3,000/mm3 
• 
Absolute Neutrophil Count (ANC) ≥1,200/mm3 
• 
Hemoglobin (Hgb) ≥9 g/dL 
• 
Platelet count ≥100,000/mm3 (≥100 10*9/L)  
• 
White Blood Count (WBC) ≤40 cells/µL via urinalysis 
• 
Albumin ≤300,000 mg/L via urinalysis 
7. Subject has an eGFR ≥45mL/min, ≤14 days prior to the planned index procedure 
date. 
8. International Normalized Ratio (INR) score of <1.5:  
• 
If on anticoagulants, other than aspirin or non-steroidal anti-inflammatory 
drugs, assessment must be performed on the day of the procedure; OR 
• 
If only on aspirin or non-steroidal anti-inflammatory drugs, assessment must be 
performed ≤14 days prior to the planned index procedure date; OR 
• 
If not on anticoagulants, assessment must be performed ≤14 days prior to the 
planned index procedure date 
9. Biopsy is required to determine the type of tumor and must be performed ≥14 days 
prior to the planned index procedure date. 
Imaging Inclusion 
10. The tumor selected for histotripsy treatment must be ≤3cm in longest diameter. 
11. Subject has an adequate acoustic window to visualize targeted tumor using the 
HistoSonics Investigational System. 
12. Subject will undergo histotripsy treatment of only one (1) tumor during the index 
procedure, regardless of how many tumors the subject has. 
General Exclusion 
 
Subjects are not eligible for participation in the trial if any of the following criteria are 
met: 
1. Subject is pregnant or planning to become pregnant or nursing (lactating) during the 
trial period.  
2. Subject is enrolled and being actively treated in another investigational 
pharmaceutical or device trial ≤30 days prior to planned index procedure date. 

 
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3. Subject is undergoing active chemotherapy for any cancer ≤14 days prior to planned 
index procedure date. 
4. Subject is undergoing active immunotherapy ≤40 days prior to planned index 
procedure date. 
5. 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 Investigational 
System. 
6. Subject is on dialysis or being considered for dialysis. 
7. Subject has not recovered to Common Terminology Criteria for Adverse Events 
(CTCAE) grade 2 or better from any adverse effects (except alopecia and 
neuropathy) related to previous anti-cancer therapy. 
8. Subject has an uncorrectable coagulopathy other than that induced by aspirin or 
non-steroidal anti-inflammatory drugs.  
9. Subject has a planned cancer treatment (e.g., nephrectomy, chemotherapy, 
immunotherapy etc.) prior to completion of the 30-day follow-up visit.  
10. Subject has had previous treatments with chemotherapy, radiotherapy, or both that 
have not been discontinued ≥14 days prior to the planned index procedure date and 
have not recovered (CTCAE grade 2 or better) from related toxicity (exclusive of 
alopecia and neuropathy). 
11. Subject has previous treatment with immunotherapies that has not been 
discontinued ≥40-days prior to the planned index procedure date and has not 
recovered from related toxicity (CTCAE grade 2 or better).  
12. Subject has a life expectancy less than one (< 1) year.  
13. In the investigator’s opinion, histotripsy is not a treatment option for the subject. 
14. Subject has a concurrent condition that could jeopardize the safety of the subject or 
compliance with the protocol. 
15. Subjects’ targeted tumor has had prior locoregional therapy (e.g., ablation, 
embolization, radiation). 
16. Subjects’ tumor is not treatable by the HistoSonics Investigational System’s working 
ranges (refer to User Guide).  
17. In the physician’s opinion, the anticipated risk of intervention outweighs the 
potential benefits of the intervention. 
18. Subject has acute renal failure. 
19. Subject has a genetic predisposition to kidney cancer such as:  
• 
Von Hippel Lindau (VHL)  
• 
Hereditary Papillary Renal Carcinoma (HPRC) 
• 
Birt-Hogg-Dubé Syndrome (BHD) 
• 
Tuberous Sclerosis Complex (TSC)  
• 
Hereditary Leiomyomata’s Renal Cell Carcinoma (HLRCC)  
• 
Reed’s Syndrome 

 
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• 
Succinate Dehydrogenase B Deficiency (SDHB) 
• 
BRCA 1 associated protein -1 (BAP1) Renal Cell Carcinoma  
• 
MITF predisposed Renal Cell Carcinoma  
20. Tumor is an angiomyolipoma. 
21. Subject has a known sensitivity to contrast media and cannot be adequately pre-
medicated. 
Imaging Exclusion 
22. The targeted tumor is not clearly visible with diagnostic ultrasound and either 
magnetic resonance imaging (MRI) or computerized tomography (CT). 
23. Targeted tumor with adequate margin overlaps the renal pelvis, main renal vessel, 
ureter, or other vital structure. 
24. Targeted tumor with adequate margin overlaps a non-targeted tumor visible via 
imaging. 
25. The treatment of the tumor will not allow for an adequate margin as determined by 
the investigator. 
Statistical Methods 
All endpoints will be summarized descriptively with 95% (Wilson) confidence intervals. 
As a pilot trial, no formal hypotheses will be defined; the endpoints are designed to 
provide additional information for the development of a pivotal trial. 
Sponsor 
HistoSonics, Inc. 
16305 36th Avenue North, Suite 300 
Plymouth, MN 55446 
United States of America (USA) 
+1 (612) 351-0361