Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis
Study Details
Study Description
Brief Summary
This phase I trial studies the side effects and best dose of hypofractionated radiosurgery in treating patients with large brain metastasis. Stereotactic radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Giving fractionated stereotactic radiosurgery may kill more tumor cells.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
PRIMARY OBJECTIVE:
To demonstrate the safety and feasibility of treating brain metastases or resection cavities greater than 3 cm with hypofractionated radiosurgery and to determine the maximum-tolerated radiation dose for hypofractionated radiosurgery (HR) delivered in 5 fractions, 2-3 fractions per week.
OUTLINE: This is a dose-escalation study.
Patients undergo hypofractionated stereotactic radiosurgery 2-3 times weekly (5 fractions total) for 2-3 weeks.
After completion of study treatment, patients are followed up at 1 month and then every 3 months thereafter.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Hypofractionated Radiosurgery HR (Hypofractionated Radiosurgery) delivered in 5 fractions, with a minimum of 2 and a maximum of 3 fractions being delivered per week, to patients with brain metastases or resection cavity greater than 3 cm and less than 6 cm. Dose escalation will proceed according to the Escalation with Overdose Control (EWOC) method with a planned total enrollment of 24 patients, in 8 patient cohorts with 3 patients per cohort. A 4 month observation period will occur for each completed cohort prior to dose escalation, with a goal timeline for trial completion of 4 years from first patient enrollment. |
Radiation: Hypofractionated Radiosurgery
Radiation Therapy will consist of partial brain irradiation delivered to the metastatic brain tumor or resection cavity, delivered in 5 treatments with 2-3 treatments delivered per week.
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) of hypofractionated radiosurgery defined as the highest dose level where a grade 3 or greater with an attribution score of ≥ 3 develops in ≤ 2 of 6 patients in a dose group [4 months]
Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. The rate of toxicities will be calculated with 95% confidence interval (CI).
- Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03 [Up to 2 years]
Calculated with 95% CI.
Secondary Outcome Measures
- Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria [4 months]
The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.
- Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria [4 months]
The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.
- Freedom from failure/progression free survival [Up to 2 years]
- Overall survival (OS): death from any cause [Up to 2 years]
The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
- Long-term neurocognitive outcomes: using the Hopkins Verbal Learning Test-Revised (HVLT-R), Mini Mental Status Exam (MMSE) and Cognitive Functioning Subscale of the Medical Outcomes Scale (MOS) [Up to 2 years]
Neurocognitive effect will be regressed over time using generalized estimating equation (GEE) model. The population change over time (slope) will be estimated with 95% CI.
- Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br). [Up to 2 years]
QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Pathologic proven diagnosis of solid tumor malignancy
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One brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)
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Recursive partitioning analysis (RPA) class I-II/ Karnofsky Performance status (KPS) ≥ 70%
Exclusion Criteria:
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Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 Gy
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RPA class III (KPS < 70%)
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Brain metastasis or resection cavity volume < 3 cm or > 6 cm
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Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies
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Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation)
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Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology
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Current pregnancy
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More than 8 weeks between resection and radiosurgical procedure
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Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
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Inability to undergo MRI evaluation for treatment planning and follow-up
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emory University Hospital/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 2 | Emory Saint Joseph's Hospital | Atlanta | Georgia | United States | 30342 |
Sponsors and Collaborators
- Emory University
Investigators
- Principal Investigator: Bree Eaton, MD, Emory University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB00055063
- NCI-2012-01933
- RAD2156-11