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

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.

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