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Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

Primary Purpose

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

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hypofractionated Radiosurgery
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Malignant Neoplasm to Brain focused on measuring Brain metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Emory University Hospital/Winship Cancer Institute
  • Emory Saint Joseph's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hypofractionated Radiosurgery

Arm Description

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.

Outcomes

Primary Outcome Measures

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).
Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
Calculated with 95% CI.

Secondary Outcome Measures

Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.
Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria
The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.
Freedom from failure/progression free survival
Overall survival (OS): death from any cause
The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
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)
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.
Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.

Full Information

First Posted
October 10, 2012
Last Updated
May 8, 2023
Sponsor
Emory University
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01705548
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 24, 2012 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Malignant Neoplasm to Brain, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
Brain metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hypofractionated Radiosurgery
Arm Type
Experimental
Arm Description
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.
Intervention Type
Radiation
Intervention Name(s)
Hypofractionated Radiosurgery
Intervention Description
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 Measure Information:
Title
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
Description
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).
Time Frame
4 months
Title
Neurologic toxicity due to treatment, graded according to the CTCAE version 4.03
Description
Calculated with 95% CI.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Local control; lack of progression of disease in resection cavity as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
Description
The median time to local brain progression will be calculated by Kaplan-Meier method with 95% CI.
Time Frame
4 months
Title
Distant control: lack of progression of disease in surrounding brain as defined by RECIST criteria
Description
The median time to distant brain progression will be calculated by Kaplan-Meier method with 95% CI.
Time Frame
4 months
Title
Freedom from failure/progression free survival
Time Frame
Up to 2 years
Title
Overall survival (OS): death from any cause
Description
The median of OS time with 95% CI will be calculated by Kaplan-Meier method.
Time Frame
Up to 2 years
Title
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)
Description
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.
Time Frame
Up to 2 years
Title
Quality of life (QOL) outcomes: using the quality of life questionnaire for the Functional Assessment of Cancer Therapy-Brain (FACT-Br).
Description
QOL outcomes will be regressed over time using GEE model. The population change over time (slope) will be estimated with 95% CI.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bree Eaton, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States

12. IPD Sharing Statement

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Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis

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