Metastatic Malignant Neoplasm to BrainNCT01705548
Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis
A study testing Hypofractionated Radiosurgery in people with Metastatic Malignant Neoplasm to Brain and Unspecified Adult Solid Tumor, Protocol Specific, run by Emory University at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm to Brain, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- Hypofractionated Radiosurgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Sep 2012to 18 Sep 2023
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342
About this study
Official title: Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis
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.
Read the 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.
- Being tested
- Hypofractionated Radiosurgery
- Keywords
- Brain metastasis
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypofractionated RadiosurgeryRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: Hypofractionated Radiosurgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 months
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.
Number
Measured: 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
Cumulative incidences of local brain progression will be calculated by Kaplan-Meier method with 95% CI.
Measured: 24 months
Intercranial Progression Free Survival: Lack of Progression of Disease in Surrounding Brain as Defined by RECIST Criteria
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.
Measured: 12 months
Freedom From Failure/Progression Free Survival
Measured: Up to 2 years
Overall Survival (OS): Death From Any Cause
The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
Measured: Up to 2 years
Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Scores
Percentage of Participants with a Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Z-Score of ≤ -1.
Measured: Up to 4 months
Quality of Life (QOL) Outcomes: Using the Quality of Life Questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2012 (estimated)
- Study start24 Sep 2012
- Primary completion11 Apr 2023
- Study completion18 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Malignant Neoplasm to BrainStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Bree Eaton, Emory University
- Investigators
- Bree Eaton, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01705548
- Sponsor's protocol ID
- IRB00055063
- Other IDs
- NCI-2012-01933, RAD2156-11, P30CA138292
- Status last verified
- Apr 2026
- First submitted
- 10 Oct 2012
- Last updated
- 7 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes