Neoplasm Metastasis
Conditions
Keywords
Metastatic lung tumors, Pulmonary metastatic disease
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.
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.
Interventions
DEVICECryoablation
Application of extremely cold temperatures to the identified tumor(s).
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cryoablation 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. | 128 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 18 |
| Overall Study | Entered Hospice or Similar Program | 2 |
| Overall Study | Index Tumor(s) Resected | 2 |
| Overall Study | Index Tumor was Primary Lung Cancer | 2 |
| Overall Study | Local therapy, not cryoablation | 6 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Cryoablation |
|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 60 Participants |
| Number of Index Tumors Per Participant 1 Tumor | 79 Participants |
| Number of Index Tumors Per Participant 2 Tumors | 23 Participants |
| Number of Index Tumors Per Participant 3 Tumors | 15 Participants |
| Number of Index Tumors Per Participant 4 Tumors | 5 Participants |
| Number of Index Tumors Per Participant 5 Tumors | 2 Participants |
| Number of Index Tumors Per Participant 6 Tumors | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 59 Participants |
| Race (NIH/OMB) White | 62 Participants |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 130 |
| other Total, other adverse events | 70 / 130 |
| serious Total, serious adverse events | 18 / 130 |
Outcome results
Primary
Local Tumor Control for Each Index Tumor as Measured by Imaging at 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.
Time frame: Month 1 (Month 3 if Month 1 Data was missing) and Month 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Cryoablation | Local Tumor Control for Each Index Tumor as Measured by Imaging at Month 12 | 84.6 percentage of tumors |
Comparison: 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.p-value: 0.41Random effects logistic regression model
Secondary
Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect
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
Population: Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed (ITT Population).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Intra-operative serious adverse event | 4 Participants |
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Post-operative serious adverse event | 4 Participants |
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Unanticipated adverse device effect | 0 Participants |
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Intra-operative nonserious adverse event | 39 Participants |
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Post-operative nonserious adverse event | 18 Participants |
| Cryoablation | Number of Participants With an Intra- or Post-operative Adverse Event, a Serious Adverse Event, or an Unanticipated Adverse Device Effect | Serious adverse events | 15 Participants |
Other Pre-specified
Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 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.
Time frame: Baseline, Month 1, Month 3, Month 6, Month 12, Month 18, and Month 24
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 6 | -1.08 units on a scale | Standard Deviation 8.35 |
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 12 | -1.86 units on a scale | Standard Deviation 8.64 |
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 24 | -5.00 units on a scale | Standard Deviation 16.02 |
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 1 | -1.14 units on a scale | Standard Deviation 6.8 |
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 3 | -1.34 units on a scale | Standard Deviation 8.12 |
| Cryoablation | Change From Baseline in Physical Function as Assessed by the Karnofsky Performance Status (KPS) Scale at Months 1, 3, 6, 12, 18, and 24 | Month 18 | -3.82 units on a scale | Standard Deviation 12.29 |
Other Pre-specified
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
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cryoablation | 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 | Physical Functioning, Month 1 | -3.9 units on a scale | Standard Deviation 28.5 |
| Cryoablation | 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 | Physical Functioning, Month 3 | -3.2 units on a scale | Standard Deviation 28.7 |
| Cryoablation | 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 | Role Physical, Month 1 | 1.6 units on a scale | Standard Deviation 34.3 |
| Cryoablation | 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 | Role Physical, Month 3 | 3.9 units on a scale | Standard Deviation 35.9 |
| Cryoablation | 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 | Social Functioning, Month 1 | 3.3 units on a scale | Standard Deviation 23.7 |
| Cryoablation | 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 | Social Functioning, Month 3 | 0.9 units on a scale | Standard Deviation 29.1 |
| Cryoablation | 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 | Mental Health, Month 1 | 2.9 units on a scale | Standard Deviation 20.1 |
| Cryoablation | 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 | Mental Health, Month 3 | 3.0 units on a scale | Standard Deviation 23.1 |
| Cryoablation | 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 | Role Emotional, Month 3 | 2.6 units on a scale | Standard Deviation 24.8 |
| Cryoablation | 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 | Vitality, Month 1 | -2.7 units on a scale | Standard Deviation 29.4 |
| Cryoablation | 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 | Bodily Pain, Month 1 | -1.6 units on a scale | Standard Deviation 26.6 |
| Cryoablation | 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 | Bodily Pain, Month 3 | -2.4 units on a scale | Standard Deviation 26.4 |
| Cryoablation | 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 | Role Emotional, Month 1 | -2.0 units on a scale | Standard Deviation 25.8 |
| Cryoablation | 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 | Vitality, Month 3 | -1.3 units on a scale | Standard Deviation 29.7 |
| Cryoablation | 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 | General Health Perception, Month 1 | -2.3 units on a scale | Standard Deviation 25.1 |
| Cryoablation | 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 | General Health Perception, Month 3 | -2.2 units on a scale | Standard Deviation 23.7 |
Other Pre-specified
Cryoablation Technical Success at 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.
Time frame: Up to Month 1
Population: Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cryoablation | Cryoablation Technical Success at Month 1 | 97.2 percentage of tumors |
Other Pre-specified
Local Tumor Control for Each Index Tumor at 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.
Time frame: Month 1 (Month 3 if Month 1 Data was missing), Month 18 and Month 24
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cryoablation | Local Tumor Control for Each Index Tumor at Month 18 and Month 24 | Month 18 | 82.3 percentage of tumors |
| Cryoablation | Local Tumor Control for Each Index Tumor at Month 18 and Month 24 | Month 24 | 75.1 percentage of tumors |
Other Pre-specified
Local Tumor Control With Additional Cryoablation Galil Medical Technology Treatment(s) of a Previously Treated Index Tumor
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Cryoablation | Local Tumor Control With Additional Cryoablation Galil Medical Technology Treatment(s) of a Previously Treated Index Tumor | 100 percentage of tumors |
Other Pre-specified
Overall Participant Survival Post-cryoablation
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
Population: Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cryoablation | Overall Participant Survival Post-cryoablation | 0-7 Days | 100 percentage of participants |
| Cryoablation | Overall Participant Survival Post-cryoablation | 8-30 Days | 100 percentage of participants |
| Cryoablation | Overall Participant Survival Post-cryoablation | 31-90 Days | 100 percentage of participants |
| Cryoablation | Overall Participant Survival Post-cryoablation | 91-180 Days | 100 percentage of participants |
| Cryoablation | Overall Participant Survival Post-cryoablation | 181-365 Days | 97.6 percentage of participants |
| Cryoablation | Overall Participant Survival Post-cryoablation | 366-730 Days | 86.6 percentage of participants |
Other Pre-specified
Time to Metastatic Lung Disease Progression Beyond the Index Tumor(s)
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
Population: Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cryoablation | Time to Metastatic Lung Disease Progression Beyond the Index Tumor(s) | 515 days |
Other Pre-specified
Time to Overall Cancer Progression
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
Population: Participants for whom cryoablation via Galil Medical Cryoablation System was attempted or performed and met all study entry criteria (mITT population).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cryoablation | Time to Overall Cancer Progression | 173 days |
Other Pre-specified
Time to Untreatable Metastatic Lung Disease Control With Cryoablation (Free From Metastatic Lung Disease)
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cryoablation | Time to Untreatable Metastatic Lung Disease Control With Cryoablation (Free From Metastatic Lung Disease) | Month 12 (Days 181-365) | 83.3 percentage of participants |
| Cryoablation | Time to Untreatable Metastatic Lung Disease Control With Cryoablation (Free From Metastatic Lung Disease) | Month 24 (Days 495-730) | 72.2 percentage of participants |
Other Pre-specified
Time to Untreatable Metastatic Lung Disease Control With Focal Therapy (Free From Metastatic Lung Disease)
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cryoablation | Time to Untreatable Metastatic Lung Disease Control With Focal Therapy (Free From Metastatic Lung Disease) | Month 12 (Days 181-365) | 81.7 percentage of participants |
| Cryoablation | Time to Untreatable Metastatic Lung Disease Control With Focal Therapy (Free From Metastatic Lung Disease) | Month 24 (Days 495-730) | 72.4 percentage of participants |