ClinicalTrials.gov
ClinicalTrials.gov Menu

Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01705548
Recruitment Status : Recruiting
First Posted : October 12, 2012
Last Update Posted : August 20, 2018
Sponsor:
Information provided by (Responsible Party):
Bree Eaton, Emory University

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.

Condition or disease Intervention/treatment Phase
Metastatic Malignant Neoplasm to Brain Unspecified Adult Solid Tumor, Protocol Specific Radiation: Hypofractionated Radiosurgery Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Trial of Hypofractionated Radiosurgery for Large Brain Metastasis
Study Start Date : September 2012
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : July 2022

Arm Intervention/treatment
Experimental: Hypofractionated Radiosurgery

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
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.




Primary Outcome Measures :
  1. 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 [ Time Frame: 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).

  2. Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03 [ Time Frame: Up to 2 years ]
    Calculated with 95% CI.


Secondary Outcome Measures :
  1. Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria [ Time Frame: 4 months ]
    The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.

  2. Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria [ Time Frame: 4 months ]
    The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.

  3. Freedom from failure/progression free survival [ Time Frame: Up to 2 years ]
  4. Overall survival (OS): death from any cause [ Time Frame: Up to 2 years ]
    The median of OS time with 95% CI will be calculated by Kaplan-Meier method.

  5. 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) [ Time Frame: Up to 2 years ]
    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.

  6. Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br). [ Time Frame: Up to 2 years ]
    QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic proven diagnosis of solid tumor malignancy
  • Solitary brain metastasis or brain metastasis resection cavity with maximal diameter ≥ 3 cm (or ≥ 14 cc.) and ≤ 6 cm (or ≤ 113 cc.)
  • Mini Mental Status Exam (MMSE) ≥ 18 prior to study entry
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01705548


Contacts
Contact: Bree Eaton, MD 404-778-3473 brupper@emory.edu

Locations
United States, Georgia
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Bree Eaton, MD    404-778-3473    brupper@emory.edu   
Contact: Jamila Beasley    404-778-1242    jamila.beasley@emoryhealthcare.org   
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Bree Eaton, MD Emory University

Responsible Party: Bree Eaton, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01705548     History of Changes
Other Study ID Numbers: IRB00055063
NCI-2012-01933 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RAD2156-11 ( Other Identifier: Winship Cancer Institute )
First Posted: October 12, 2012    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018

Keywords provided by Bree Eaton, Emory University:
Brain metastasis

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Brain Diseases
Neoplasms
Neoplasms, Second Primary
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases