Cryoablation Combined With Stereotactic Body Radiation Therapy for the Treatment of Painful Bone Metastases, the CROME Trial

PRIMARY OBJECTIVE:

I. To determine the efficacy of cryoablation in combination with stereotactic body radiation therapy (SBRT) or SBRT only for the treatment of painful bone metastases.

SECONDARY OBJECTIVES:

I. To assess for narcotics utilization by daily morphine equivalent dose. II. To assess duration of pain response reported by International Pain Response Criteria.

III. To assess for local tumor control. IV. To assess for changes in patient quality of life with Brief Pain Inventory (BPI) score.

V. To assess for adverse event rates. VI. To assess incidence and severity of adverse events/toxicity. VII. To assess technical success for cryoablation.

EXPLORATORY OBJECTIVE:

I. To investigate the local microenvironmental changes following SBRT and cryoablation combined with SBRT to bone metastases.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo stereotactic body radiation therapy for 1 fraction.

ARM B: Patients undergo cryoablation. Within 10 days after cryoablation, patients undergo stereotactic body radiation therapy for 1 fraction.

After completion of study treatment, patients are followed up at 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks.

Inclusion criteria

• Patient must have a primary diagnosis of malignancy and radiographic evidence of bone metastases. Eligible tumor histologies include the following malignancies with low alpha/beta ratios: renal cell carcinoma, urothelial carcinomas, castration-resistant prostate cancer, sarcoma, thyroid carcinoma, colorectal carcinoma, and melanoma
• A target lesion the meets the following criteria:

• The target lesion must be amenable to both cryoablation and SBRT, as determined by the study principal investigators (PIs)
• The target lesion must be =< 7cm
• The pain due to the target lesion must be at least 4/10 based on the BPI pain scale
• Pain from the metastatic site must correlate with an identifiable tumor on computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US) imaging
• Life expectancy >= 3 months
• Platelet count > 50,000/mm^3 within 6 weeks of screening
• International normalized ratio (INR) < 1.5 within 6 weeks of screening
• If taking antiplatelet or anticoagulation medication, it must be able to be discontinued 48 hours prior to the procedure or at the discretion of the PI (e.g., aspirin, ibuprofen, low molecular weight heparin [LMWH] preparations)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) within 6 weeks of screening
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization. Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization
• All lines of prior systemic therapy are permissible. Standard concurrent chemotherapy, immunotherapy, or targeted therapy are permissible
• Ability to understand and the willingness to sign a written informed consent document

Exclusion criteria

• Prior locoregional therapy to target lesion, including ablation of any modality, embolization, radiation, or surgery
• Patient may not be receiving any other investigational agents. Standard concurrent chemotherapy, immunotherapy, or targeted therapy will be allowed
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or nursing women; women of childbearing potential unless using effective contraception as determined by the investigator
• Target lesions that involve the spinal column or calvarium
• Absolute neutrophil count < 1000 mm^3 within 6 weeks of screening
• Active infection
• Presence of confirmed pathologic fracture at the target lesion not amenable to percutaneous stabilization
• Lesions that involve a weight-bearing long bone of the lower extremity with the tumor causing > 50% loss of cortical bone. Lesions involving the hands and feet