Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01705548
• Other study ID #: IRB00055063
• Secondary ID: NCI-2012-01933RA
• Status: Completed
• Phase: N/A
• Start date: September 24, 2012
• Est. completion date: September 18, 2023

Study information

• Verified date: January 2024
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 18, 2023
• Est. primary completion date: April 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Malignant Neoplasm to Brain
• Neoplasm Metastasis
• Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

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.

Locations

Country	Name	City	State
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia

Sponsors (3)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).	4 months
Primary	Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03	Calculated with 95% CI.	Up to 2 years
Secondary	Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria	The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.	4 months
Secondary	Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria	The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.	4 months
Secondary	Freedom from failure/progression free survival		Up to 2 years
Secondary	Overall survival (OS): death from any cause	The median of OS time with 95% CI will be calculated by Kaplan-Meier method.	Up to 2 years
Secondary	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)	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.	Up to 2 years
Secondary	Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).	QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.	Up to 2 years