Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

Not Applicable

Completed

Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Metastatic Malignant Neoplasm to Brain

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.

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.

Recruitment & Eligibility

Inclusion Criteria

Pathologic proven diagnosis of solid tumor malignancy
One brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)
Recursive partitioning analysis (RPA) class I-II/ Karnofsky Performance status (KPS) ≥ 70%

Exclusion Criteria

Prior stereotactic radiosurgery (SRS) to adjacent lesion such that planning target volume would have received more than 12 Gy
RPA class III (KPS < 70%)
Brain metastasis or resection cavity volume < 3 cm or > 6 cm
Radiosensitive or non-solid (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies
Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation)
Evidence of leptomeningeal disease by magnetic resonance imaging (MRI) and/or cerebrospinal fluid (CSF) cytology
Current pregnancy
More than 8 weeks between resection and radiosurgical procedure
Metastases to brain stem, midbrain, pons, or medulla or within 5 mm of the optic apparatus (optic nerves and chiasm)
Inability to undergo MRI evaluation for treatment planning and follow-up

Arm && Interventions

Group	Intervention	Description
Hypofractionated Radiosurgery	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.

Primary Outcome Measures

Name	Time	Method
Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03	Up to 2 years	Calculated with 95% CI.
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).

Secondary Outcome Measures

Name	Time	Method
Freedom from failure/progression free survival	Up to 2 years
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.
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.

Locations (2): Emory Saint Joseph's Hospital
🇺🇸
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States