Adaptive Staged Stereotactic Body Radiation Therapy in Treating Patients With Spinal Metastases That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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This pilot clinical trial studies adaptive staged stereotactic body radiation therapy (SBRT) in treating patients with spinal metastases that cannot be removed by surgery. SBRT is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may kill more tumor cells and cause less damage to normal tissue. Adaptive SBRT uses information gathered during treatment to inform, guide, and alter future radiation treatments. Staged SBRT uses multiple treatments separated by 2-3 weeks. Giving adaptive staged SBRT may work better in treating spinal metastases that cannot be removed by surgery.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the feasibility of single-fraction radiotherapy to provide a short-interval treatment response in patients with metastatic epidural spinal cord compression (MESCC), such that additional stereotactic radiotherapy to full therapeutic doses can be delivered while respecting spinal cord constraints, based on the following metrics: shortest distance between gross disease and the spinal cord before and after treatment; epidural tumor volume before and after treatment; and extent of epidural compression before and after treatment. SECONDARY OBJECTIVES: I. To evaluate pain control using the Numerical Rating Pain Scale (NRPS) before and after treatment. II. To evaluate patient quality of life using the Functional Assessment of Cancer Therapy-General (FACT-G) before and after treatment. III. To evaluate functional outcomes using ambulation score and standardized neurologic exams before and after treatment. OUTLINE: Patients undergo adaptive staged SBRT. Within 14-21 days, patients may undergo a second treatment of adaptive staged SBRT at the discretion of the treating physician based on clinical parameters, diagnostic interval imaging, and achievement of spinal cord dose constraints. After completion of study treatment, patients are followed up periodically.

Official Title
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Adaptive Staged Stereotactic Body Radiation Therapy in Treating Patients With Spinal Metastases That Cannot Be Removed by Surgery

Conditions
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Melanoma, Metastatic Malignant Neoplasm in the Spine, Renal Cell Carcinoma, Soft Tissue Sarcoma, Spinal Cord Compression

Intervention / Treatment
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* Radiation: Image-Guided Adaptive Radiation Therapy
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Radiation: Stereotactic Body Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Localized spine metastasis from the cervical (C)1 to lumbar (L)5 levels with documented epidural cord compression by a screening imaging study (magnetic resonance imaging [MRI] or computed tomography [CT] myelogram); site may have a maximal involvement of 2 contiguous vertebral bodies; patients with other visceral metastasis, and radioresistant tumors (including soft tissue sarcomas, melanomas, and renal cell carcinomas) are eligible History/physical examination by the treating physician within 24 hours prior to registration Neurological and functional examination within 24 hours prior to registration by the treating physician Negative serum pregnancy test MRI (contrast is not required but strongly recommended) or CT myelogram of the involved spine within 1 week prior to registration to determine the extent of the spine involvement Numerical rating pain scale within 1 week prior to registration; documentation of the patient's initial pain score is required; patients taking medication for pain at the time of registration are eligible Women of childbearing potential must: Have a negative serum or urine pregnancy test within 72 hours prior to the start of study therapy Agree to utilize an adequate method of contraception throughout treatment and for at least 4 weeks after study therapy is completed Be advised of the importance of avoiding pregnancy during trial participation and the potential risks of an unintentional pregnancy All patients must sign study specific informed consent prior to study entry or within 1 week of first treatment, provided other criteria were met Patients considered for enrollment are strongly recommended to have been discussed at multidisciplinary tumor board with input from surgery, medical oncology and radiation oncology prior to enrollment Exclusion Criteria: Histologies of myeloma or lymphoma Cord compression at 2 non-contiguous sites in the spine Favorable candidates for surgical decompression by prior documented criteria Spine instability as determined by Spinal Instability Neoplastic Score (SINS) score > 12 > 50% loss of vertebral body height Bony retropulsion causing neurologic abnormality Prior radiation to the index spine Patients who cannot obtain a contrast-enhanced MRI or CT myelogram due to allergy, renal failure or other medical contraindication

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (adaptive staged SBRT)<br>Patients undergo adaptive staged SBRT. Within 14-21 days, patients may undergo a second treatment of adaptive staged SBRT at the discretion of the treating physician based on clinical parameters, diagnostic interval imaging, and achievement of spinal cord dose constraints. | Radiation: Image-Guided Adaptive Radiation Therapy<br>* Undergo adaptive staged SBRT<br>* Other names: IGART;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Radiation: Stereotactic Body Radiation Therapy<br>* Undergo adaptive staged SBRT<br>* Other names: SBRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic response of the spinal tumor, as measured by a reduction in the epidural tumor volume greater than or equal to 10% after treatment on imaging scans (MRI or CT myelogram) | Data will be summarized using standard descriptive statistics; formal hypothesis testing will not be performed. Confidence intervals for the true proportion will be computed using Clopper-Pearson exact confidence interval. The width shows that the response rate will not be lower than 20%. Since this is a feasibility, study no power calculation is done. | Up to 10 weeks after first treatment | 
| Radiographic response of the spinal tumor, as measured by a reduction in thecal sac compression by greater than or equal to 10% after treatment on imaging scans (MRI or CT myelogram) | Data will be summarized using standard descriptive statistics; formal hypothesis testing will not be performed. Confidence intervals for the true proportion will be computed using Clopper-Pearson exact confidence interval. The width shows that the response rate will not be lower than 20%. Since this is a feasibility, study no power calculation is done. | Up to 10 weeks after first treatment | 
| Radiographic response of the spinal tumor, as measured by distance between the gross disease and spinal cord greater than or equal to 3 mm after treatment on imaging scans (MRI or CT myelogram) | Data will be summarized using standard descriptive statistics; formal hypothesis testing will not be performed. Confidence intervals for the true proportion will be computed using Clopper-Pearson exact confidence interval. The width shows that the response rate will not be lower than 20%. Since this is a feasibility, study no power calculation is done. | Up to 10 weeks after first treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ambulation based on ambulation score and standardized neurologic exam | Data will be reported in a descriptive manner. | Baseline to week 10 after first treatment | 
| Change in pain control in terms of pain scores as measured by the NRPS estimation | Data will be reported in a descriptive manner. | Baseline to week 10 after first treatment | 
| Change in quality of life scores from FACT-G | Data will be reported in a descriptive manner. | Baseline to up to 3 months | 
| Incidence of any grade greater than or equal to 3 treatment-related toxicity, scored using CTCAE, v. 4 | Data will be reported in a descriptive manner. | Up to 2 years | 
| Incidence of grade greater than or equal to 2 radiation-induced lung toxicity, scored using Common Toxicity Criteria for Adverse Events (CTCAE), version (v.) 4 | Data will be reported in a descriptive manner. | Up to 2 years | 
| Overall survival | Data will be reported in a descriptive manner. | From study registration to death, censored at the date of data collection, assessed up to 2 years | 
| Progression-free survival | Data will be reported in a descriptive manner. | From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 2 years |