Cryoablation of Low Risk Breast Cancer Less Than 1.5 cm: An Evaluation of Local Recurrence (Ice3 Trial)
Phase: NA
Conditions: Breast Cancer
Sponsor: IceCure Medical Ltd.

 
Protocol Number: ICM-BC-02 
Date: Oct 27, 2021 
Version:18.1    
ICE3 Study – Clinical Study Synopsis  
Page 1 of 3 
 
IceCure Medical Ltd. Proprietary and Confidential 
 
Cryoablation of Low-Risk Breast Cancers less than 1.5 cm: An evaluation of local 
recurrence (Ice3 Trial) – ICMBC-02 
Study Plan- Synopsis 
Study Title 
 
Cryoablation of Low-Risk Breast Cancers less than 1.5 cm: An evaluation 
of local recurrence (Ice3 Trial) 
Investigational 
Device 
PROSENSE™ 
Study Sites and 
Participants 
212 subjects/ 19 sites  
Device Description 
 
IceCure Medical's PROSENSE™ cryogenic system (also branded as 
ICESENSE3™) is intended for cryogenic destruction of tissue (utilizes 
Liquid Nitrogen) during surgical procedures (minimally invasive image-
guided), by the application of extreme cold temperatures.  
The PROSENSE™ system has FDA clearance (K183213) for use as a 
cryosurgical tool in the fields of general surgery (including breast 
fibroadenomas), dermatology, neurology, thoracic surgery, ENT, 
gynecology, oncology, proctology, and urology. 
Study Design  
Multi-centered, single arm, non-randomized clinical trial.  
Patients will undergo imaging by mammography, ultrasound and breast 
MRI (optional) pre-registration to ensure eligibility. All fully eligible and 
registered patients will then be treated with cryoablation therapy 
followed by 6 month and annual mammograms and physical 
examinations for 5 years post treatment. 
Study Objectives 
The goal of this study is to evaluate the safety and efficacy, in terms of 
Ipsilateral Breast Tumor Recurrence (IBTR) rate of cryoablation using 
IceCure medical’s PROSENSE™ device for the treatment of low-risk early 
breast cancer in women 50 years or older. 
Study Endpoints  
 
Primary endpoint: 
Local Ipsilateral Breast Tumor Recurrence (IBTR) rate. 
Secondary endpoints: 
• Complete ablation of primary tumor rates up to 60 months after 
cryoablation.  
• Improvement or maintenance of subject’s quality of life at 6 months 
compared to baseline. 

 
Protocol Number: ICM-BC-02 
Date: Oct 27, 2021 
Version:18.1    
ICE3 Study – Clinical Study Synopsis  
Page 2 of 3 
 
IceCure Medical Ltd. Proprietary and Confidential 
 
• Breast cosmetics satisfaction. 
• Regional Invasive breast tumor recurrence rate. 
• Distant metastases rate including contralateral Breast cancer.  
• Disease–free Survival (DFS) from date of complete ablation of the 
primary tumor, until the first disease event where the disease event 
is defined as local (DCIS or invasive), regional, or distant breast cancer 
recurrence, second primary cancer, DCIS or invasive contralateral 
breast cancer, or death due to any cause. 
• Overall survival from the date of the cryoablation until the date of 
death from any cause or up to the 60 months follow up visit. 
• Breast Cancer Survival from the date of cryoablation until the date of 
death from breast cancer or up to the 60 months follow-up visit. 
Subjects who died without a specified cause will be considered as 
events (i.e., due to breast cancer). 
• Adverse events related to study device or procedure rate. 
Study Population 
Women aged 50 or older, with low-risk breast carcinoma, less or equal 
to 1.5 cm in diameter, will be enrolled into the study. 
Main Eligibility 
Criteria 
1. Diagnosis of invasive ductal breast carcinoma by core needle biopsy, 
meeting the following criteria: 
a. Unifocal primary disease 
b. Tumor size <1.5 cm in greatest diameter  
c. Nottingham grade 1-2.  
d. Estrogen receptor positive, and or progesterone receptor 
positive, HER2 negative,  
2. Age ≥ 50 (Local IRB), Age ≥ 60 (WCG IRB) 
3. Breast size adequate for safe cryoablation. 
4. Lesion must be sonographically visible at the time of treatment. 
5. History of previously treated ipsilateral or contralateral breast 
carcinoma is not an exclusion criteria if the investigator is certain 
newly diagnosed carcinoma is new unifocal primary tumor. 

 
Protocol Number: ICM-BC-02 
Date: Oct 27, 2021 
Version:18.1    
ICE3 Study – Clinical Study Synopsis  
Page 3 of 3 
 
IceCure Medical Ltd. Proprietary and Confidential 
 
Exclusion Criteria 
1. Presence of lobular carcinoma 
2. Presence of luminal B pathology 
3. Nottingham score of 3  
4. Presence of microinvasion or invasive breast carcinoma with 
extensive intraductal component (EIC)  
5. Presence of multifocal and/or multicentric in breast cancer 
6. Presence of multifocal calcifications 
7. Presence of prior or concurrent neoadjuvant chemotherapy for breast 
cancer 
8. Presence of prior en bloc open surgical biopsy and/or lumpectomy for 
diagnosis/treatment of the index breast cancer  
9. Patient that is not suitable to cryoablation procedure according to the 
physician opinion 
10. ER AND PR negative, or Her2 positive noted on pre-cryo biopsy  
Statistical analysis- 
General 
considerations 
Statistical analyses will be performed using SAS® v9.3 or higher (SAS 
Institute, Cary NC, USA). 
Statistical tests performed will be two-sided. The required significance 
level of findings will be equal to or lower than 5%. Where the confidence 
level will be 95%. 
Baseline values are defined as the last valid value prior to study 
treatment start. All statistical analyses of safety and performance 
measures will be descriptive in nature. Continuous variables will be 
summarized by a mean, standard deviation, minimum, median and 
maximum, and categorical variables by a count and percentage. 
Confidence intervals will be provided where relevant.  
The study results will be discussed comparatively to data published of 
similar products.