Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

September 14, 2022 updated by: Alliance for Clinical Trials in Oncology

Phase III Randomized Trial of the Role of Whole Brain Radiation Therapy in Addition to Radiosurgery in Patients With One to Three Cerebral Metastases

RATIONALE: Stereotactic radiation therapy can send x-rays directly to the tumor and cause less damage to normal tissue. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether stereotactic radiation therapy is more effective with or without whole-brain radiation therapy in treating patients with brain metastases.

PURPOSE: This randomized phase III trial is studying stereotactic radiation therapy and whole-brain radiation therapy to see how well they work compared with stereotactic radiation therapy alone in treating patients with brain metastases.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the overall survival of patients with 1 to 3 cerebral metastases treated with stereotactic radiosurgery with vs without whole-brain radiotherapy.

Secondary

  • Compare time to CNS (brain) failure in patients treated with these regimens.
  • Compare quality of life, duration of functional independence, and long-term neurocognitive status of patients treated with these regimens.
  • Compare post-treatment toxicity in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (18 to 59 vs 60 and over), extracranial disease (controlled for ≤ 3 months vs controlled for > 3 months), and number of brain metastases (1 vs 2 vs 3). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo stereotactic radiosurgery (SRS).
  • Arm II: Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks.

Quality of life, functional independence, and neurocognitive status are assessed at baseline, at the beginning of each treatment, at weeks 6 and 12, and then at 6, 9, 12, 16, 24 , 36, 48, and 60 months.

PROJECTED ACCRUAL: A total of 238 patients will be accrued for this protocol.

Study Type

Interventional

Enrollment (Actual)

213

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre - Calgary
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Margaret and Charles Juravinski Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CHUS-Hopital Fleurimont
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85027
        • Arizona Oncology-Deer Valley Center
      • Scottsdale, Arizona, United States, 85260
        • Arizona Oncology Services Foundation
    • California
      • Modesto, California, United States, 95355
        • Memorial Medical Center
      • Oakland, California, United States, 94611
        • Kaiser Permanente - Division of Research - Oakland
      • Orange, California, United States, 92868
        • St. Joseph Hospital Regional Cancer Center - Orange
      • Rohnert Park, California, United States, 94928
        • Rohnert Park Cancer Center
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
      • Santa Rosa, California, United States, 95403
        • Kaiser Permanente Medical Center - Santa Rosa
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center at UC Health Sciences Center
      • Denver, Colorado, United States, 80220
        • Veterans Affairs Medical Center - Denver
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic - Jacksonville
      • Orlando, Florida, United States, 32803-1273
        • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • Georgia
      • Atlanta, Georgia, United States, 30342-1611
        • Northside Hospital Cancer Center
      • Atlanta, Georgia, United States, 30342-1701
        • Saint Joseph's Hospital of Atlanta
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center
      • Savannah, Georgia, United States, 31405
        • Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
    • Illinois
      • Arlington Heights, Illinois, United States, 60005
        • Northwest Community Hospital
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0093
        • Lucille P. Markey Cancer Center at University of Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Owensboro Mercy Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Cancer Institute at Ochsner Clinic Foundation
    • Massachusetts
      • Lowell, Massachusetts, United States, 01854
        • Lowell General Hospital
      • Worcester, Massachusetts, United States, 01608
        • Saint Vincent Hospital at Worcester Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48202
        • Josephine Ford Cancer Center at Henry Ford Hospital
      • Kalamazoo, Michigan, United States, 49007-3731
        • West Michigan Cancer Center
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • CCOP - Duluth
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
      • Saint Cloud, Minnesota, United States, 56303
        • CentraCare Clinic - River Campus
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Cancer Institute of Cape Girardeau, LLC
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Cancer Institute at Saint Luke's Hospital
    • Montana
      • Billings, Montana, United States, 59107-7000
        • Billings Clinic - Downtown
    • Nebraska
      • Omaha, Nebraska, United States, 68122
        • Immanuel Medical Center
    • New Hampshire
      • Dover, New Hampshire, United States, 03820
        • Seacoast Cancer Center at Wentworth - Douglass Hospital
      • Manchester, New Hampshire, United States, 03103
        • Elliot Regional Cancer Center at Elliot Hospital
    • New Jersey
      • Somerville, New Jersey, United States, 08876
        • Somerset Medical Center
      • Toms River, New Jersey, United States, 08755
        • J. Phillip Citta Regional Cancer Center at Community Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center/Levine Cancer Institute
      • Charlotte, North Carolina, United States, 28232-2861
        • Blumenthal Cancer Center at Carolinas Medical Center
      • Fayetteville, North Carolina, United States, 28302-2000
        • Cape Fear Valley Medical Center Cancer Center
      • Wilmington, North Carolina, United States, 28401
        • Coastal Carolina Radiation Oncology Center
      • Winston-Salem, North Carolina, United States, 27103
        • Forsyth Regional Cancer Center at Forsyth Medical Center
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Bismarck, North Dakota, United States, 58501
        • Medcenter One Hospital Cancer Care Center
    • Ohio
      • Akron, Ohio, United States, 44309-2090
        • Summa Center for Cancer Care at Akron City Hospital
      • Salem, Ohio, United States, 44460
        • Cancer Care Center, Incorporated
      • Wooster, Ohio, United States, 44691
        • Cancer Treatment Center
    • Oregon
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital & Comprehensive Cancer Center
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822-0001
        • Geisinger Cancer Institute at Geisinger Health
      • Philadelphia, Pennsylvania, United States, 19114
        • Frankford Hospital Cancer Center - Torresdale Campus
    • South Carolina
      • Greenville, South Carolina, United States, 29615
        • CCOP - Greenville
      • Greenville, South Carolina, United States, 29605
        • Cancer Centers of the Carolinas - Faris Road
      • Greenville, South Carolina, United States, 29615
        • Greenville Cancer Center of the Carolinas (CCOP)
    • Texas
      • Galveston, Texas, United States, 77555
        • University of Texas Medical Branch
    • Washington
      • Vancouver, Washington, United States, 98686
        • Legacy Salmon Creek Medical Center
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54307-3508
        • St. Vincent Hospital Regional Cancer Center
      • Racine, Wisconsin, United States, 53405
        • All Saints Cancer Center at Wheaton Franciscan Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of cerebral metastases meeting the following criteria:

    • One to three presumed brain metastases

    • Metastases must be from a histologically confirmed extracerebral site (e.g., lung, breast, prostate)

      • Histologic confirmation may have been from the primary tumor site, from another metastatic site (e.g., osseous metastasis, adrenal metastasis), or from the metastatic brain lesion(s)
    • Each lesion must measure less than 3.0 cm by contrast MRI of the brain performed within the past 21 days
    • Lesions must not be within 5 mm of the optic chiasm or within the brainstem
  • Eligibility for treatment with gamma knife or linear accelerator-based radiosurgery confirmed by a radiation oncologist
  • No primary germ cell tumor, small cell carcinoma, or lymphoma
  • No leptomeningeal metastases
  • Hormone receptor status not specified

PATIENT CHARACTERISTICS:

  • Male or female
  • Menopausal status not specified
  • ECOG performance status 0-2
  • Not pregnant
  • Negative pregnancy test

  • Fertile patients must use effective contraception

    • Male patients must continue to use contraception for 3 months after the completion of radiotherapy
  • No pacemaker or other MRI-incompatible metal in the body
  • No known allergy to gadolinium

PRIOR CONCURRENT THERAPY:

  • More than 7 days since prior and no concurrent chemotherapy
  • No prior cranial radiotherapy
  • No prior resection of cerebral metastases
  • Concurrent hormonal agents, steroids, and/or anticonvulsants allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I
Patients undergo stereotactic radiosurgery (SRS)
Radiation: stereotactic radiosurgery
Experimental: Arm II
Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks.
Radiation: stereotactic radiosurgery
Radiation: radiation therapy
Patients undergo radiation therapy 5 days a week for 2.5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months
Time Frame: 3 months post radiosurgery
The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.
3 months post radiosurgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Local and Distant Tumor Control up to 3 Months
Time Frame: Up to 3 months
Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....
Up to 3 months
Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]
Time Frame: From Baseline to 3-Month Evaluation
Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.
From Baseline to 3-Month Evaluation
Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months
Time Frame: From baseline to 12 months
Long-Term Neurocognitive Status > To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.
From baseline to 12 months
Overall Survival
Time Frame: Up to 5 years
Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Paul D. Brown, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2006

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

December 15, 2019

Study Registration Dates

First Submitted

September 13, 2006

First Submitted That Met QC Criteria

September 13, 2006

First Posted (Estimate)

September 15, 2006

Study Record Updates

Last Update Posted (Actual)

September 16, 2022

Last Update Submitted That Met QC Criteria

September 14, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N0574
  • NCCTG-N0574
  • ACOSOG-N0574
  • CDR0000499633 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-2009-00653 (Registry Identifier: CTRP (Clinical Trials Reporting System))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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