Clinical trial NCT01705548: Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis
Official title: Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metastatic Malignant Neoplasm to Brain
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: Brain metastasis
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2012-10-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 4 months
measure: Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
timeFrame: Up to 2 years
Secondary outcomes:
measure: Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
timeFrame: 4 months
measure: Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria
timeFrame: 4 months
measure: Freedom from failure/progression free survival
timeFrame: Up to 2 years
measure: Overall survival (OS): death from any cause
timeFrame: Up to 2 years
measure: 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)
timeFrame: Up to 2 years
measure: Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Bree Eaton, MD
role: PRINCIPAL_INVESTIGATOR
References: