Safety and Efficacy of Cryoablation Combined With Radiation Therapy for the Palliation of Painful Bone Metastases

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the safety and efficacy of cryoablation therapy combined with radiation therapy for the relief of pain associated with metastatic bone tumors.

Detailed Description
-----------------
Patients with painful bone metastases who meet the eligibility criteria and who have been determined to be an appropriate candidate for cryoablation therapy and radiation therapy will be offered enrollment into the study. 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). Radiation therapy, also called radiotherapy, uses carefully targeted doses of high-energy radiation to kill cancer cells. Radiation is used to treat many kinds of cancer. Patients agreeing to participate will read and sign an informed consent form and thus become subjects in the study. Treatment will be performed using a Galil Medical cryoablation system and Galil Medical cryoablation needles. Subjects will be followed for up to 24 weeks (6 months) for palliation of pain, quality of life and analgesic usage. Baseline and follow-up data will be collected for each subject via a web-based electronic data collection tool.

Official Title
-----------------
Cryoablation Combined With Radiation Therapy for the Palliation of Painful Bone Metastases

Conditions
-----------------
Pain, Neoplasm Metastasis

Intervention / Treatment
-----------------
* Procedure: Cryoablation
* Procedure: Radiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older Metastatic bone disease with metastatic disease previously confirmed by prior biopsy; or Metastatic bone disease previously confirmed on imaging [e.g. computed tomography (CT) or magnetic resonance imaging (MRI)] with known (biopsied) primary disease (primary bone cancer is excluded) Current analgesic therapies have failed OR the subject is experiencing intolerable side effects Unremitting pain that resulted in a return visit to the oncologist. The 'worst pain' in the last 24 hours must be reported to be 4 or above on a scale of 0 (no pain) to 10 (pain as bad as subject can imagine) despite pharmaceutical pain management Pain must be from one or two painful metastatic sites in the bone that is amenable to cryoablation with CT or MRI (additional less painful metastatic sites may be present) • Pain from the reported one or two metastatic sites must correlate with an identifiable tumor on CT, MRI, or ultrasound (US) imaging Tumors must be suitable for cryoablation If the primary tumor is in the spine, there must be an intact cortex between the mass and the spinal canal and exiting nerve roots Cryoablation should be performed within 14 days of baseline evaluations Stable use of hormonal therapy (no changes within 4 weeks prior to the cryoablation procedure) Stable use of pain medications (no changes within 2 weeks prior to the cryoablation procedure) ECOG (Eastern Cooperative Oncology Group) scale performance status 0-3 Life expectancy ≥ 2 months Platelet count >50,000/mm³ within 6 weeks of screening INR (International Normalized Ratio) <1.5 within 6 weeks of screening No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment and follow-up If taking antiplatelet or anticoagulation medication, it must be able to be discontinued prior to the procedure for an appropriate amount of time (e.g., aspirin, ibuprofen, low molecular weight heparin preparations) Clinically suitable for cryoablation therapy Clinically suitable for radiation therapy Exclusion Criteria: Leukemia, lymphoma, and myeloma Tumor involves a weight-bearing long bone of the lower extremity with the tumor causing > 50% loss of cortical bone Has undergone prior ablation treatment of the index tumor Has undergone prior radiation therapy of the index tumor < 3 weeks prior to screening Index tumor causing clinical or radiographic evidence of spinal cord or cauda equina compression/effacement Anticipated treatment of the index tumor that would require iceball formation within 1.0 cm of the spinal cord, brain, other critical nerve structure, large abdominal vessel such as the aorta or inferior vena cava, bowel, or bladder Surgery at the tumor site or surgery involving the cryoablation-treated tumor Index tumor involves the skull (treatment of other painful tumors in subjects with skull tumors is not excluded) ANC (absolute neutrophil count) <1000 mm3 within 6 weeks of screening Uncontrolled coagulopathy or bleeding disorders Currently pregnant, nursing, or wishing to become pregnant during the study Active, uncontrolled infection Serious medical illness, including any of the following: uncontrolled congestive heart failure, uncontrolled angina, myocardial infarction, cerebrovascular event within 6 months prior to study entry Concurrent participation in other experimental studies that could affect the primary endpoint

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cryoablation combined with radiation<br>All subjects will have cryoablation combined with radiation on one or two painful metastatic bone tumors. | Procedure: Cryoablation<br>* For cryoablation in the palliation of painful bone metastases, subject preparation, anesthesia, intra-operative monitoring, and postoperative management are identical to those of standard cryoablation routinely performed at all clinical centers participating in this study and are at the discretion of the investigator.<br>* Other names: IceSphere Cryoablation Needle;Procedure: Radiation<br>* Radiation therapy is usually performed with 6-18 Megavolt photons from a linear accelerator. The proposed dose and frequency of radiation for this protocol are: 8 Gray in 1 fraction, 30 Gray in 10 fractions, or 37.5 Gray in 15 fractions. These proposed doses or other doses will be prescribed at the discretion of the investigator. It is anticipated that subjects will begin the radiation therapy approximately within one to three weeks after the cryoablation procedure. The doses and frequency of the radiation treatment will be collected as well as toxicities.<br>* Other names: Radiotherapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in worst pain scores | The endpoint for this study will be measured as follows: assessment of the effectiveness of cryoablation combined with radiation associated with palliation of pain in subjects with metastatic bone cancer by measuring the average difference of pre- and posttreatment worst pain in 24 hours from baseline to 24 hour, 1, 4, 12, and 24 week follow-up intervals as measured on the numeric 0 to 10 Brief Pain Inventory (BPI) scale. | 24 weeks post cryoablation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cryoablation retreatments | If the first cryoablation procedure effectively relieves pain but the relief wears off over time and the pain becomes unbearable, a second procedure may be performed. The number of repeat cryoablation treatments will be recorded. | 24 weeks post-cryoablation | 
| Additional surgical treatments other than cryoablation | If pain is not effectively relieved by the cryoablation, other surgical treatments may be performed. The number of these treatments will be recorded. | 24 weeks post-cryoablation | 
| Reduced analgesic usage | The number of subjects (percentage) who are able to reduce analgesic medications from baseline to 24 hours, 1, 4, 12, and 24 weeks after cryoablation will be recorded. | 24 weeks post-cryoablation | 
| Time to maximal palliation of pain after cryoablation | The difference in pain scores will be assessed from baseline to follow-up intervals after cryoablation will be analyzed. The interval indicating the most relief from pain will be compared across subjects. | 24 weeks post-cryoablation | 
| Number of adverse events | The safety endpoint for this study is to assess the incidence and severity of intra-operative events, post operative adverse events, serious adverse events and unanticipated adverse device effects related to the cryoablation procedure. | 30 days post-cryoablation | 
| Difference in average pain scores | Difference in average pain scores from baseline to 24 hours, 1, 4, 12, and 24 weeks after cryoablation as measured on the numeric 0 to 10 BPI scale | 24 weeks post-cryoablation | 
| Time to recurrence of worst pain | Time to recurrence of worst pain at or above baseline; worst pain score in the 24 week follow-up period as measured on the numeric 0 to 10 BPI scale | 24 weeks post-cryoablation | 
| Subject satisfaction with the amount of palliation of pain obtained from cryoablation combined with radiation | Subject satisfaction will be compared at baseline to follow-up intervals. | 24 weeks post-cryoablation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Painful bone metastases, Bone metastases, Metastatic bone tumors, Metastatic bone pain, Cryoablation, Cryotherapy, Cryosurgery, Radiation therapy, Radiotherapy