Metastatic Malignant Neoplasm to Brain, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
Brain metastasis
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.
Interventions
RADIATIONHypofractionated 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.
Sponsors
Emory University
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Percentage of Participants With Neurologic Toxicity/Radiation Necrosis Possibly Due to Treatment, Graded According to the CTCAE Version 4.03 as Grade 2 or Greater. | Up to 2 years | Number |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Control; Lack of Progression of Disease in Resection Cavity as Defined by Response Evaluation Criteria In Solid Tumors (RECIST) Criteria | 24 months | Cumulative incidences of local brain progression will be calculated by Kaplan-Meier method with 95% CI. |
| Intercranial Progression Free Survival: Lack of Progression of Disease in Surrounding Brain as Defined by RECIST Criteria | 12 months | Percentage of patients with distant brain progression at the defined time point, with each individual patient's time to progression 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. |
| Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Scores | Up to 4 months | Percentage of Participants with a Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Z-Score of ≤ -1. |
| 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 | Patients completed the FACT-BR at baseline and in follow-up. Responses are summed at each encounter to create a score. Total assessments combine scores range from 0-200. The higher the score, the better the QOL. Change from baseline to 4-month follow-up was calculated. A notable change is defined 20 point or greater increase or decrease in total score from baseline to 4-month follow-up score. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBree Eaton, MD
Emory University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 67 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 6 / 12 | 6 / 9 |
| other Total, other adverse events | 3 / 3 | 12 / 12 | 9 / 9 |
| serious Total, serious adverse events | 0 / 3 | 0 / 12 | 3 / 9 |
Outcome results
None listed