SOLSTICE: Study of Cryoablation for Metastatic Lung Tumors

• Sponsor: Boston Scientific Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01957787
• Collaborator: (none)
• Enrollment: 131
• Locations: 10
• Arm: 1
• Actual Duration (Months): 52.3
• Patients Per Site: 13.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of cryoablation therapy used to treat tumors in participants with pulmonary metastatic disease. This study is to enroll participants who will undergo cryoablation of at least 1 metastatic pulmonary tumor that is less than or equal to 3.5 centimeter (cm). Participants will be followed 24 months post their cryoablation procedure.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Metastasis	Device: Cryoablation	N/A

Detailed Description

Treatment for pulmonary metastatic disease may include surgery, chemotherapy, radiation therapy, or a combination of treatments. However, several variables may exclude participants from these treatments such as multiple tumors, multiple previous surgeries, pulmonary dysfunction, or co-morbid medical conditions. For these participants, percutaneous cryoablation may be a suitable option.

Ablation of metastatic lung tumors is a rapidly expanding area within interventional oncology. Cryotherapy, radiofrequency, laser, and microwave have all been shown to be effective. Cryotherapy offers a wide range of anatomic and tumor treatment options because of the ability to visualize the ice under imaging guidance and the preservation of collagenous tissue structure. Cryoablation has been extensively performed in the prostate and kidney with favorable outcomes reported in the literature. More recently, cryoablation has been shown to be safe in the treatment of lung tumors with CT guidance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation
• Actual Study Start Date: Apr 10, 2014
• Actual Primary Completion Date: Mar 9, 2017
• Actual Study Completion Date: Aug 20, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Cryoablation Participants will undergo a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure will be identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and will be at the discretion of the Investigators. Tumors in both lungs are to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session will not be performed. All participants will receive cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors are to be completed within an 8-week window.

Device: Cryoablation; Application of extremely cold temperatures to the identified tumor(s).; Other Names: Cryotherapy Visual-ICE® Cryoablation System PresIce® Cryoablation System SeedNet® Cryoablation System IceEDGE® 2.4 Cryoablation Needles IceRod® PLUS Cryoablation Needles IceSphere™ Cryoablation Needles

Outcome Measures

Primary Outcome Measures

1. Local Tumor Control for Each Index Tumor as Measured by Imaging at Month 12 [Month 1 (Month 3 if Month 1 Data was missing) and Month 12]

   Local tumor control defined as the absence of local treatment failure 12 months following study cryoablation based on site-reported data. Local control was achieved if the 3-axis measurement (that is, the greatest trans-axial diameter plus the 2 perpendicular diameters) of a tumor at Month 12 was less than 20% larger than the 3-axis measurement of the tumor at Month 1 following study cryoablation. A separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Month 1 data served as the baseline for this analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at the prior study visit and those with repeat cryoablation procedures prior to Month 12 were counted as failures. Imaging for assessment of tumor measurements was performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.

Secondary Outcome Measures

1. Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect [Baseline up to 30 days post-cryoablation]

   The number of participants with the following categories of adverse events is presented: an intra-operative, a post-operative, a serious adverse event, or an unanticipated adverse device effect. The adverse events that are presented are related to the cryoablation procedure. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.

Other Outcome Measures

1. Local Tumor Control for Each Index Tumor at Month 18 and Month 24 [Month 1 (Month 3 if Month 1 Data was missing), Month 18 and Month 24]

   Local tumor control defined as the absence of local treatment failure 18 and 24 months following study cryoablation based on site-reported data. Local control was achieved if the 3-axis measurement (that is, the greatest trans-axial diameter plus the 2 perpendicular diameters) of a tumor at Month 12 was less than 20% larger than the 3-axis measurement of the tumor at Month 1 following study cryoablation. A separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Month 1 data served as the baseline for this analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at the prior study visit and those with repeat cryoablation procedures prior to Month 12 were counted as failures. Imaging for assessment of tumor measurements was performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.

2. Overall Participant Survival Post-cryoablation [Up to Month 24]

   Overall survival rate was defined as the time in days from the first cryoablation procedure to death. Participants who were alive were censored at the date of the last visit.

3. Time to Metastatic Lung Disease Progression Beyond the Index Tumor(s) [Up to Month 24]

   Time to metastatic lung disease progression beyond the index tumor was defined as the time in days from the first cryoablation procedure to metastatic disease beyond the index tumor site. Participants without metastatic lung disease progression were censored at the date of their last visit or their date of death (due to any cause).

4. Time to Overall Cancer Progression [Up to Month 24]

   Time to overall cancer progression was defined as the time in days from the first cryoablation procedure to cancer progression (that is, any location of active cancer disease). Participants without cancer progression were censored at the date of their last visit or their date of death (due to any cause).

5. Local Tumor Control With Additional Cryoablation Galil Medical Technology Treatment(s) of a Previously Treated Index Tumor [Up to Month 12]

   Local tumor control, defined as absence of local treatment failure 12 months following study cryoablation based on site-reported data, was achieved if 3-axis measurement (that is, greatest trans-axial diameter plus 2 perpendicular diameters) of a tumor at Month 12 was <20% larger than 3-axis measurement of the tumor at Month 1 following study cryoablation. Separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Follow-up visits were re-started after additional treatment, per study protocol and continued through the Month 24 visit after the last study cryoablation. Month 1 data served as baseline for analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at prior study visit and with repeat cryoablation procedures prior to Month 12 were counted as failures. Tumor measurement imaging performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.

6. Time to Untreatable Metastatic Lung Disease Control With Cryoablation (Free From Metastatic Lung Disease) [Month 12 (Days 181-365) and Month 24 (Days 495-730)]

   Time to untreatable metastatic lung disease control with cryoablation is defined as the time in days from the first cryoablation procedure to the time when the metastatic lung disease cannot be treated with cryoablation. The percentage of participants free from metastatic disease that is untreatable with cryoablation at the intervals of time of Days 181 to 365 and Days 495 to 730 is presented.

7. Time to Untreatable Metastatic Lung Disease Control With Focal Therapy (Free From Metastatic Lung Disease) [Month 12 (Days 181-365) and Month 24 (Days 495-730)]

   Time to untreatable metastatic lung disease control with focal therapy defined as the time in days from the first cryoablation procedure to the time when the metastatic lung disease cannot be treated by focal (for example, ablation, surgery, SBRT) intervention for control of metastatic lung disease. The percentage of participants free from metastatic disease that is untreatable with focal therapy at the intervals of time of Days 181 to 365 and Days 495 to 730 is presented.

8. Cryoablation Technical Success at Month 1 [Up to Month 1]

   A technically successful treatment was defined by the presence of an ablation zone, ground glass opacity, or frank consolidation encompassing the targeted index tumor(s) at no later than the 1 month follow up visit after the cryoablation procedure. Technical success rates and 95% confidence intervals (CIs) were calculated using random effects logistic regression on a tumor level.

9. Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 [Baseline, Month 1, Month 3, Month 6, Month 12, Month 18, and Month 24]

   The KPS scale is a standard way of measuring the ability of cancer participants to perform ordinary tasks. KPS may be used to determine a participant's prognosis and to measure changes in a participant's ability to function. Assessments were made by examining the change in the baseline scores to those reported post-operatively. KPS scores range from 0 to 100. A higher score means the participant is better able to carry out daily activities.

10. Change From Baseline in Quality of Life Over Time as Assessed by the Short Form-12 (SF-12) Generic Measure at Month 1 and Month 3 [Baseline, Month 1 and Month 3]

    The SF-12 is a shortened version of the well-known SF-36. The SF-12 assesses 8 domains (physical functioning, role limitations due to physical health problems, bodily pain, social functioning, general mental health, role limitations due to emotional problems, vitality, general health perception). The shorter instrument provides a general measurement of quality of life. Assessments were made by examining the change in the baseline scores to those reported post-operatively. The scores range from 0 to 100. A higher value indicates a better quality of life of the participant.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant must be at least 18 years old.

• Participant has signed a written informed consent.

• Participant presents with Stage 4 pulmonary metastatic disease with metastatic disease previously confirmed by prior biopsy; or Participant presents with Stage 4 pulmonary metastatic disease previously confirmed on imaging (for example, computerized tomography or CT) with histology proven primary cancer.

• Participant has up to 6 local pulmonary metastases targetable by cryoablation.

• Targeted index tumor(s) defined as intra pulmonary or pleural with a maximum size of 3.5 cm, measured in the longest cross-sectional dimension.

• The target index tumor(s) is determined (by CT images) to be in a location where cryoablation is technically achievable based on the proximity of adjacent organs/ structures and is greater than 0.5 cm from any critical organ/structure (possibly achieved with additional maneuvers such as iatrogenic pneumothorax or hydrodissection).

• Karnofsky Performance Scale (KPS) score greater than or equal to 60.

• Platelet count greater than 50,000/millimeters (mm)^3 within 8 weeks prior to initial cryoablation procedure.

• International Normalized Ratio (INR) less than 1.5 within 8 weeks prior to initial cryoablation procedure.

• Participant has a life expectancy of greater than 3 months.

Exclusion Criteria:

• Participant's index tumor(s) is primary lung cancer.

• Participant has uncontrollable primary or metastatic disease outside of the lung.

• Participant is unable to lie flat or has respiratory distress at rest.

• Participant has a coagulopathy or bleeding disorder which is uncontrolled.

• Absolute Neutrophil Count (ANC) <1000 within 8 weeks prior to initial cryoablation procedure.

• Participant has evidence of active systemic, pulmonary, or pericardial infection.

• Participant has a debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment or follow up.

• Participant is currently participating in other experimental studies that could affect the primary endpoint (for example, experimental chemotherapy regimen).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Ronald Reagan Medical Center	Los Angeles	California	United States	90095
2	Cancer Treatment Centers of America at Southeastern Regional Medical Center	Newnan	Georgia	United States	30265
3	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
5	New York Presbyterian Hospital - Cornell Medical Center	New York	New York	United States	10065
6	State University of New York at Stony Brook	Stony Brook	New York	United States	11794
7	Rhode Island Hospital	Providence	Rhode Island	United States	02903
8	Inova Alexandria Hospital CVIR	Alexandria	Virginia	United States	22304
9	Institut Bergonié	Bordeaux	Aquitaine	France	33070
10	Institut Gustave Roussy	Villejuif	Ile-de-France	France	94805

Sponsors and Collaborators

• Boston Scientific Corporation

Investigators

• Study Chair: Thierry de Baere, MD, Gustave Roussy, Cancer Campus, Grand Paris
• Study Chair: Matthew Callstrom, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol - Feb 3, 2014
• Statistical Analysis Plan - Jan 4, 2017

More Information

Publications

• Ahmed A, Littrup P. Percutaneous cryotherapy of the thorax: safety considerations for complex cases. AJR Am J Roentgenol. 2006 Jun;186(6):1703-6.
• Asimakopoulos G, Beeson J, Evans J, Maiwand MO. Cryosurgery for malignant endobronchial tumors: analysis of outcome. Chest. 2005 Jun;127(6):2007-14.
• Gillams A. Lung tumour ablation - where are we now? Cancer Imaging. 2008 Apr 22;8:116-7. doi: 10.1102/1470-7330.2008.0015.
• Inoue M, Nakatsuka S, Yashiro H, Ito N, Izumi Y, Yamauchi Y, Hashimoto K, Asakura K, Tsukada N, Kawamura M, Nomori H, Kuribayashi S. Percutaneous cryoablation of lung tumors: feasibility and safety. J Vasc Interv Radiol. 2012 Mar;23(3):295-302; quiz 305. doi: 10.1016/j.jvir.2011.11.019. Epub 2012 Jan 20.
• Kawamura M, Izumi Y, Tsukada N, Asakura K, Sugiura H, Yashiro H, Nakano K, Nakatsuka S, Kuribayashi S, Kobayashi K. Percutaneous cryoablation of small pulmonary malignant tumors under computed tomographic guidance with local anesthesia for nonsurgical candidates. J Thorac Cardiovasc Surg. 2006 May;131(5):1007-13.
• Pusceddu C, Sotgia B, Fele RM, Melis L. CT-guided thin needles percutaneous cryoablation (PCA) in patients with primary and secondary lung tumors: a preliminary experience. Eur J Radiol. 2013 May;82(5):e246-53. doi: 10.1016/j.ejrad.2012.12.010. Epub 2013 Feb 8.
• Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures. Radiology. 2005 Apr;235(1):289-98.
• Yamauchi Y, Izumi Y, Kawamura M, Nakatsuka S, Yashiro H, Tsukada N, Inoue M, Asakura K, Nomori H. Percutaneous cryoablation of pulmonary metastases from colorectal cancer. PLoS One. 2011;6(11):e27086. doi: 10.1371/journal.pone.0027086. Epub 2011 Nov 9.

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT01957787
• Other Study ID Numbers: CUC13-LNG079
• First Posted: Oct 8, 2013
• Last Update Posted: Jul 19, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Boston Scientific Corporation: Metastatic lung tumors; Pulmonary metastatic disease
• Additional relevant MeSH terms: Neoplasm Metastasis; Lung Neoplasms

Study Results

Participant Flow

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Period Title: Overall Study
STARTED	131
Intent-to-Treat (ITT) Population	130
Modified ITT (mITT) Population	128
COMPLETED	95
NOT COMPLETED	36

Baseline Characteristics

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Overall Participants	128
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (11.9)
Sex: Female, Male (Count of Participants)
Female	60 46.9%
Male	68 53.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 3.9%
Not Hispanic or Latino	63 49.2%
Unknown or Not Reported	60 46.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 3.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 1.6%
White	62 48.4%
More than one race	0 0%
Unknown or Not Reported	59 46.1%
Number of Index Tumors Per Participant (Count of Participants)
1 Tumor	79 61.7%
2 Tumors	23 18%
3 Tumors	15 11.7%
4 Tumors	5 3.9%
5 Tumors	2 1.6%
6 Tumors	4 3.1%

Outcome Measures

1. Primary Outcome

Title	Local Tumor Control for Each Index Tumor as Measured by Imaging at Month 12
Description	Local tumor control defined as the absence of local treatment failure 12 months following study cryoablation based on site-reported data. Local control was achieved if the 3-axis measurement (that is, the greatest trans-axial diameter plus the 2 perpendicular diameters) of a tumor at Month 12 was less than 20% larger than the 3-axis measurement of the tumor at Month 1 following study cryoablation. A separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Month 1 data served as the baseline for this analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at the prior study visit and those with repeat cryoablation procedures prior to Month 12 were counted as failures. Imaging for assessment of tumor measurements was performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.
Time Frame	Month 1 (Month 3 if Month 1 Data was missing) and Month 12

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population). Multiple imputation methods for missing data were applied.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Measure Number of Tumors	224
Number (95% Confidence Interval) [percentage of tumors]	84.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cryoablation
	Comments	The null hypothesis was tested comparing the lower bound of the Wald 97.5% 1-sided confidence interval for the estimated rate of local tumor control to the performance goal of 84.0%. If the lower bound was greater than 84.0%, the null hypothesis was rejected and the endpoint was considered met.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.410
	Comments	Estimates of the log odds and Wald standard error from a random effects logistic regression model were combined across imputed datasets for reference.
	Method	Random effects logistic regression model
	Comments

2. Secondary Outcome

Title	Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect
Description	The number of participants with the following categories of adverse events is presented: an intra-operative, a post-operative, a serious adverse event, or an unanticipated adverse device effect. The adverse events that are presented are related to the cryoablation procedure. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline up to 30 days post-cryoablation

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed (ITT Population).

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	130
Intra-operative nonserious adverse event	39 30.5%
Post-operative nonserious adverse event	18 14.1%
Serious adverse events	15 11.7%
Intra-operative serious adverse event	4 3.1%
Post-operative serious adverse event	4 3.1%
Unanticipated adverse device effect	0 0%

3. Other Pre-specified Outcome

Title	Local Tumor Control for Each Index Tumor at Month 18 and Month 24
Description	Local tumor control defined as the absence of local treatment failure 18 and 24 months following study cryoablation based on site-reported data. Local control was achieved if the 3-axis measurement (that is, the greatest trans-axial diameter plus the 2 perpendicular diameters) of a tumor at Month 12 was less than 20% larger than the 3-axis measurement of the tumor at Month 1 following study cryoablation. A separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Month 1 data served as the baseline for this analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at the prior study visit and those with repeat cryoablation procedures prior to Month 12 were counted as failures. Imaging for assessment of tumor measurements was performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.
Time Frame	Month 1 (Month 3 if Month 1 Data was missing), Month 18 and Month 24

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population). Multiple imputation methods for missing data were applied.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Measure Number of Tumors	224
Month 18	82.3
Month 24	75.1

4. Other Pre-specified Outcome

Title	Overall Participant Survival Post-cryoablation
Description	Overall survival rate was defined as the time in days from the first cryoablation procedure to death. Participants who were alive were censored at the date of the last visit.
Time Frame	Up to Month 24

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
0-7 Days	100 78.1%
8-30 Days	100 78.1%
31-90 Days	100 78.1%
91-180 Days	100 78.1%
181-365 Days	97.6 76.3%
366-730 Days	86.6 67.7%

5. Other Pre-specified Outcome

Title	Time to Metastatic Lung Disease Progression Beyond the Index Tumor(s)
Description	Time to metastatic lung disease progression beyond the index tumor was defined as the time in days from the first cryoablation procedure to metastatic disease beyond the index tumor site. Participants without metastatic lung disease progression were censored at the date of their last visit or their date of death (due to any cause).
Time Frame	Up to Month 24

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Median (95% Confidence Interval) [days]	515

6. Other Pre-specified Outcome

Title	Time to Overall Cancer Progression
Description	Time to overall cancer progression was defined as the time in days from the first cryoablation procedure to cancer progression (that is, any location of active cancer disease). Participants without cancer progression were censored at the date of their last visit or their date of death (due to any cause).
Time Frame	Up to Month 24

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Median (95% Confidence Interval) [days]	173

7. Other Pre-specified Outcome

Title	Local Tumor Control With Additional Cryoablation Galil Medical Technology Treatment(s) of a Previously Treated Index Tumor
Description	Local tumor control, defined as absence of local treatment failure 12 months following study cryoablation based on site-reported data, was achieved if 3-axis measurement (that is, greatest trans-axial diameter plus 2 perpendicular diameters) of a tumor at Month 12 was <20% larger than 3-axis measurement of the tumor at Month 1 following study cryoablation. Separate evaluation of local tumor control at Month 12 following cryoablation was completed per index tumor. Follow-up visits were re-started after additional treatment, per study protocol and continued through the Month 24 visit after the last study cryoablation. Month 1 data served as baseline for analysis; if Month 1 data was missing, Month 3 data were used. Tumors with a local failure at prior study visit and with repeat cryoablation procedures prior to Month 12 were counted as failures. Tumor measurement imaging performed using CT or 18 F-fluorodeoxyglucose positron emission tomography-CT with or without contrast.
Time Frame	Up to Month 12

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population) and underwent an additional Cryoablation Galil Medical Technology Treatment.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	13
Measure Number of Tumors	16
Number [percentage of tumors]	100

8. Other Pre-specified Outcome

Title	Time to Untreatable Metastatic Lung Disease Control With Cryoablation (Free From Metastatic Lung Disease)
Description	Time to untreatable metastatic lung disease control with cryoablation is defined as the time in days from the first cryoablation procedure to the time when the metastatic lung disease cannot be treated with cryoablation. The percentage of participants free from metastatic disease that is untreatable with cryoablation at the intervals of time of Days 181 to 365 and Days 495 to 730 is presented.
Time Frame	Month 12 (Days 181-365) and Month 24 (Days 495-730)

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population) with available data at the respective time point.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Month 12 (Days 181-365)	83.3 65.1%
Month 24 (Days 495-730)	72.2 56.4%

9. Other Pre-specified Outcome

Title	Time to Untreatable Metastatic Lung Disease Control With Focal Therapy (Free From Metastatic Lung Disease)
Description	Time to untreatable metastatic lung disease control with focal therapy defined as the time in days from the first cryoablation procedure to the time when the metastatic lung disease cannot be treated by focal (for example, ablation, surgery, SBRT) intervention for control of metastatic lung disease. The percentage of participants free from metastatic disease that is untreatable with focal therapy at the intervals of time of Days 181 to 365 and Days 495 to 730 is presented.
Time Frame	Month 12 (Days 181-365) and Month 24 (Days 495-730)

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population) with available data at the respective time point.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Month 12 (Days 181-365)	81.7 63.8%
Month 24 (Days 495-730)	72.4 56.6%

10. Other Pre-specified Outcome

Title	Cryoablation Technical Success at Month 1
Description	A technically successful treatment was defined by the presence of an ablation zone, ground glass opacity, or frank consolidation encompassing the targeted index tumor(s) at no later than the 1 month follow up visit after the cryoablation procedure. Technical success rates and 95% confidence intervals (CIs) were calculated using random effects logistic regression on a tumor level.
Time Frame	Up to Month 1

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Measure Number of Tumors	224
Number (95% Confidence Interval) [percentage of tumors]	97.2

11. Other Pre-specified Outcome

Title	Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24
Description	The KPS scale is a standard way of measuring the ability of cancer participants to perform ordinary tasks. KPS may be used to determine a participant's prognosis and to measure changes in a participant's ability to function. Assessments were made by examining the change in the baseline scores to those reported post-operatively. KPS scores range from 0 to 100. A higher score means the participant is better able to carry out daily activities.
Time Frame	Baseline, Month 1, Month 3, Month 6, Month 12, Month 18, and Month 24

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population) and evaluable KPS scores.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Month 1	-1.14 (6.80)
Month 3	-1.34 (8.12)
Month 6	-1.08 (8.35)
Month 12	-1.86 (8.64)
Month 18	-3.82 (12.29)
Month 24	-5.00 (16.02)

12. Other Pre-specified Outcome

Title	Change From Baseline in Quality of Life Over Time as Assessed by the Short Form-12 (SF-12) Generic Measure at Month 1 and Month 3
Description	The SF-12 is a shortened version of the well-known SF-36. The SF-12 assesses 8 domains (physical functioning, role limitations due to physical health problems, bodily pain, social functioning, general mental health, role limitations due to emotional problems, vitality, general health perception). The shorter instrument provides a general measurement of quality of life. Assessments were made by examining the change in the baseline scores to those reported post-operatively. The scores range from 0 to 100. A higher value indicates a better quality of life of the participant.
Time Frame	Baseline, Month 1 and Month 3

Outcome Measure Data

Analysis Population Description

Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population) and evaluable SF-12 scores.

Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
Measure Participants	128
Physical Functioning, Month 1	-3.9 (28.5)
Physical Functioning, Month 3	-3.2 (28.7)
Role Physical, Month 1	1.6 (34.3)
Role Physical, Month 3	3.9 (35.9)
Bodily Pain, Month 1	-1.6 (26.6)
Bodily Pain, Month 3	-2.4 (26.4)
Social Functioning, Month 1	3.3 (23.7)
Social Functioning, Month 3	0.9 (29.1)
Mental Health, Month 1	2.9 (20.1)
Mental Health, Month 3	3.0 (23.1)
Role Emotional, Month 1	-2.0 (25.8)
Role Emotional, Month 3	2.6 (24.8)
Vitality, Month 1	-2.7 (29.4)
Vitality, Month 3	-1.3 (29.7)
General Health Perception, Month 1	-2.3 (25.1)
General Health Perception, Month 3	-2.2 (23.7)

Adverse Events

Time Frame	Baseline up to Month 24
Adverse Event Reporting Description	Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed (ITT Population).
Arm/Group Title	Cryoablation
Arm/Group Description	Participants underwent a cryoablation procedure with the Galil Medical Cryoablation System according to the manufacturer's guidelines. Participant preparation, anesthesia, intra-operative monitoring, and postoperative management for the study cryoablation procedure were identical to those for standard cryoablation treatment routinely performed at the clinical centers that participated in this study and were at the discretion of the Investigators. Tumors in both lungs were to be treated at an appropriate interval, determined on an individual basis. Treatment of bilateral index tumors in a single treatment session was not performed. All participants received cryoablation of up to 6 metastatic lung tumors. Treatment of all study index tumors was completed within an 8-week window.
All Cause Mortality
	Cryoablation
	Affected / at Risk (%)	# Events
Total	18/130 (13.8%)
Serious Adverse Events
	Cryoablation
	Affected / at Risk (%)	# Events
Total	18/130 (13.8%)
Cardiac disorders
Coronary artery disease	1/130 (0.8%)
General disorders
Gait imbalance	1/130 (0.8%)
Infections and infestations
Abdominal infection	1/130 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	1/130 (0.8%)
Nervous system disorders
Headache	1/130 (0.8%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	3/130 (2.3%)
Hypoxia	1/130 (0.8%)
Pleural hemorrhage	1/130 (0.8%)
Pneumothorax	9/130 (6.9%)
Vascular disorders
Gaseous embolism	1/130 (0.8%)
Other (Not Including Serious) Adverse Events
	Cryoablation
	Affected / at Risk (%)	# Events
Total	70/130 (53.8%)
Cardiac disorders
Sinus tachycardia	1/130 (0.8%)
Gastrointestinal disorders
Abdominal distention	1/130 (0.8%)
Abdominal pain	1/130 (0.8%)
Diarrhea	1/130 (0.8%)
Nausea	1/130 (0.8%)
Vomiting	1/130 (0.8%)
General disorders
Bilateral leg edema	1/130 (0.8%)
Chest pain	1/130 (0.8%)
Fatigue	1/130 (0.8%)
Non-cardiac chest pain	1/130 (0.8%)
Pain at needle site	12/130 (9.2%)
Immune system disorders
Allergic reaction	1/130 (0.8%)
Infections and infestations
Device related infection	1/130 (0.8%)
Hepatic infection	1/130 (0.8%)
MRSA infected decubitus ulcer	1/130 (0.8%)
Oropharyngeal candidiasis	1/130 (0.8%)
Upper respiratory infection	1/130 (0.8%)
Injury, poisoning and procedural complications
Burn	1/130 (0.8%)
Vascular access complication	1/130 (0.8%)
Metabolism and nutrition disorders
Hyperglycemia	1/130 (0.8%)
Steroid induced hyperglycemia	1/130 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	2/130 (1.5%)
Nervous system disorders
Paresthesia	1/130 (0.8%)
Radiculitis	1/130 (0.8%)
Renal and urinary disorders
Urinary retention	1/130 (0.8%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage	15/130 (11.5%)
Cough	3/130 (2.3%)
Diaphragm paralysis	1/130 (0.8%)
Dyspnea	3/130 (2.3%)
Hypoxia	1/130 (0.8%)
Left-sided pleuritic pain	1/130 (0.8%)
Pleural effusion	2/130 (1.5%)
Pleurisy	1/130 (0.8%)
Pleuritic pain	1/130 (0.8%)
Pneumothorax	39/130 (30%)
Pulmonary edema	1/130 (0.8%)
Sore throat	2/130 (1.5%)
Skin and subcutaneous tissue disorders
Pruritus	2/130 (1.5%)
Rash on face and abdomen	1/130 (0.8%)
Vascular disorders
Hematoma	1/130 (0.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Galil Medical can require Investigator to postpone publications/presentations for up to 12 months so data from all sites can be published. Galil Medical will limit review of Investigator's draft to confirm Confidential Information is not being disclosed. If Galil Medical notes publishing Study results may affect obtaining a patent, Investigator may not publish for up to 60 days until patent application is filed. Investigator will acknowledge Galil Medical in any publication/presentation.