Safety and Efficacy of Cryoablation for Metastatic Lung Tumors

Study Overview
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Brief Summary
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ECLIPSE will evaluate the safety and efficacy of cryoablation therapy used to treat tumors less than or equal to 3.5 centimeters (cm) in participants with pulmonary metastatic disease.

Detailed Description
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ECLIPSE is a treatment, Phase 1 multicenter, prospective, single-arm study with participants serving as their own control. 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 cm. Participants will be followed for 5 years post their cryoablation procedure. Cryoablation is the process of destroying tissue by the application of extremely cold temperatures. Galil Medical Cryoablation Systems are used as a surgical tool in the fields of general surgery, dermatology (skin), neurology (nerves), chest surgery (including lung), Ears-Nose-Throat (ENT), gynecology, oncology (cancer), proctology (colon/rectal), and urology (kidney).

Official Title
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Evaluating Cryoablation of Metastatic Lung/Pleura Tumors in Patients - Safety and Efficacy

Conditions
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Metastatic Lung Cancer

Intervention / Treatment
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* Device: Cryoablation


Participation Criteria
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Eligibility Criteria
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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 confirmed on imaging with known primary disease. Participant has up to 3 local metastases unilaterally targeted by cryoablation. Maximum of 5 total pulmonary tumors bilaterally. Targeted tumor(s) defined as intra pulmonary or pleural with a maximum size of 3.5 cm. The target tumor is determined (by CT/MRI) to be in a location where cryoablation is technically achievable based on the proximity of adjacent organs and structures. Eastern Cooperative Oncology Group (ECOG) score of 0-2. Karnofsky Performance Scale (KPS) score ≥60. Platelet count >50,000/cubed millimeters (mm^3) within 60 days prior to study treatment. International normalized ratio (INR) less than 1.5 within 60 days prior to study treatment. Participant has a life expectancy of >3 months. Participant is clinically suitable for cryoablation procedure. Exclusion Criteria: Participant's primary cancer is lung cancer. Participant is unable to lie flat or has respiratory distress at rest. Participant has uncontrolled coagulopathy or bleeding disorders. Participant has had chemotherapy with neutropenia to levels as confirmed by absolute neutrophil count (ANC) of less than 1000 that produce increase risk for the cryoablation procedure. Participant has a history of an allergic reaction to iodine injections or to shellfish. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All participants received the same treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cryoablation<br>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. No more than 3 tumors in 1 lung can be treated in a single session, and no more than 5 total lung tumors (across both lungs) can be treated during the study. | Device: Cryoablation<br>* Application of extremely cold temperatures to the identified tumor(s).<br>* Other names: IceEDGE™ 2.4 Cryoablation Needles;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tumor Control for Each Index Tumor as Measured by Imaging at Month 60 | Local tumor control was achieved if either the greatest trans-axial diameter of a treated tumor was ≤20% greater than at the pre-procedure assessment (per-tumor assessment) or if the sum of greatest trans-axial diameters of all treated tumors for a participant was ≤20% greater than the sum for the pre-procedure assessment of those tumors (per-participant assessment). Complete Response defined as tumor disappearance (scar) or <25% of original size. If tumor/ablation zone had likely disappeared, the measurement was recorded as 0 mm; if tumor/ablation zone was present but too small to measure, the measurement was recorded as 5 mm. Partial Response defined as greater than 30% decrease in sum of the largest diameter of all targeted tumors. Stable Disease defined as less than 30% decrease in sum of the largest diameter of all targeted tumors. Local Failure defined as greater than 20% increase in the sum of the largest diameter of all targeted tumors. Worst response per participant was used. | Baseline and Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tumor Control for Each Index Tumor as Measured by Imaging at Months 3, 6, 12, 24, 36, and 48 | Local tumor control was achieved if the greatest trans-axial diameter of a treated tumor was ≤20% greater than at the pre-procedure assessment (per-tumor assessment) or if the sum of the greatest trans-axial diameters of all treated tumors for a participant was ≤20% greater than the sum for the pre-procedure assessment of those tumors (per-participant assessment). Complete Response defined as tumor disappearance (scar) or <25% of original size. If tumor/ablation zone had likely disappeared, the measurement was recorded as 0 mm; if tumor/ablation zone was present but too small to measure, the measurement was recorded as 5 mm. Partial Response defined as greater than 30% decrease in sum of the largest diameter of all targeted tumors. Stable Disease defined as less than 30% decrease in sum of the largest diameter of all targeted tumors. Local Failure defined as greater than 20% increase in the sum of the largest diameter of all targeted tumors. Worst response per participant was used. | Baseline and Months 3, 6, 12, 24, 36, and 48 | 
| Overall Disease-Specific Participant Survival Post-Cryoablation | Disease-specific survival was analyzed as time in days from study cryoablation to participant death due to lung cancer. All deaths with documented lung disease progression were categorized as disease-specific deaths for this analysis. Participants who were alive were censored at the date of their last visit. Participants who died from causes other than lung cancer and did not have documented disease progression were censored at the time of death. | Up to Month 60 | 
| Time in Days to Disease Recurrence or Progression Following Study Cryoablation | Disease recurrence or progression will be determined locally by evidence of an increase in tumor size and/or contrast enhancement that met the definition of local tumor failure. Local tumor failure defined as a >20% increase from baseline in the sum of the largest diameter of all targeted tumors. Participants without disease recurrence or progression were censored at the date of their last visit or their date of death due to any cause. The percentage of participants with disease recurrence or progression after the study cryoablation procedure at the specified number of days is presented. | Baseline (0 days), Week 1 (7 days), and Months 3 (90 days), 6 (180 days), 12 (365 days), 24 (730 days), 36 (1095 days), 48 (1460 days), and 60 (1825 days) | 
| Change From Baseline in ECOG Performance Status at Week 1 and Months 3, 6, 12, 24, 36, 48, and 60 | ECOG Performance Status defined as a set of criteria with corresponding scores used by the Investigator to assess how a participant's disease is progressing, assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. ECOG Performance Status Scoring: 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work, office work); 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead. | Baseline, Week 1 and Months 3, 6, 12, 24, 36, 48, and 60 | 
| Change From Baseline in Physical Function as Assessed by the KPS Scale at Week 1 and Months 3, 6, 12, 24, 36, 48, and 60 | The KPS Scale is a standard way of measuring the ability of cancer patients to perform ordinary tasks. The scores range from 0 to 100. A higher score means the participant is better able to carry out daily activities. KPS may be used to determine a participant's prognosis, to measure changes in a participant's ability to function. | Baseline, Week 1 and Months 3, 6, 12, 24, 36, 48, and 60 | 
| Change From Baseline in Quality of Life Over Time as Assessed by the SF-12 Generic Measure at Months 1, 3, 6, 12, 24, 36, 48, and 60 | The SF-12 is a shortened version of the well-known SF-36. The SF-12 assesses eight domains (physical functioning, role limitations due to physical health problems, bodily pain, social functioning, general mental health, role limitations due to emotional problems, vitality and general health perception). 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. | Baseline, Months 1, 3, 6, 12, 24, 36, 48, and 60 | 
| Cryoablation Technical Success of the Study Cryoablation Procedure | A technically successful treatment was defined by an ablation volume encompassing the tumor with at least a 5 mm margin. Technical success was calculated on a per tumor level as well as a participant level. To be considered a technical success on a participant level, all tumors treated during the baseline procedure were required to meet the technical success criteria (that is, an ablation volume encompassing the tumor with at least a 5 mm margin). | Up to 60 months | 
| Number of Participants With an Intra- or Post-operative Adverse Event (AE), a Serious AE, or an Unanticipated Adverse Device Effect (UADE) | An AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study. Serious AEs include death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent the previously listed serious outcomes. UADE was any serious adverse effect, any life-threatening problem or death caused by or associated with a device, if it was not previously identified in nature, severity, or degree of incidence in the application; or any other unanticipated serious problem associated with a device. The AEs that are presented were considered related to the cryoablation procedure. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | Baseline up to 30 days post-cryoablation | 
| Metastatic Disease Spread as Measured by Imaging | Evidence of additional metastatic disease post cryoablation procedure as measured by imaging is presented. | Months 3, 6, 12, 24, 36, 48, and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryoablation, Cryotherapy, Cryosurgery, Metastatic, Lung, Pleura, Tumors