Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

NCT01705548 | Completed DMC

• 4 other identifiers: IRB00055063NCI-2012-01933RAD2156-11P30CA138292
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Brain metastasis

Outcome Measures

Primary Outcomes (2)

• 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

• Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03

  Calculated with 95% CI.

  Up to 2 years

Secondary Outcomes (6)

• Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria

  4 months

• Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria

  4 months

• Freedom from failure/progression free survival

  Up to 2 years

• Overall survival (OS): death from any cause

  Up to 2 years

• 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

Study Arms (1)

Hypofractionated Radiosurgery

EXPERIMENTAL

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

Interventions

Hypofractionated Radiosurgery RADIATION

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.

Hypofractionated Radiosurgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Bree Eaton, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: October 12, 2012
• Study Start: September 24, 2012
• Primary Completion: April 11, 2023
• Study Completion: September 18, 2023
• Last Updated: January 30, 2024

Record last verified: 2024-01

Locations

US (2)