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

Phase 3
Completed
Conditions
Metastatic Cancer
Interventions
Radiation: radiation therapy
Procedure: surgery
Radiation: WBRT
Registration Number
NCT00030628
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known if radiosurgery is more effective with or without whole-brain radiation therapy in treating brain metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiosurgery with or without whole-brain radiation therapy in treating patients who have brain metastases.

Detailed Description

OBJECTIVES:

* Compare the overall survival of patients with 1 to 3 cerebral metastases treated with radiosurgery with or without whole brain radiotherapy.

* Compare the time to CNS failure (brain) in patients treated with these regimens.

* Compare the quality of life, duration of functional independence, and long-term neurocognitive status in patients treated with these regimens.

* Compare the post-treatment toxic effects of these regimens in these patients.

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

* Arm I: Patients undergo radiosurgery.

* Arm II: Patients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks.

Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.

Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 480 patients (240 per treatment arm) will be accrued for this study within 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
480
Inclusion Criteria
  • Diagnosis of cerebral metastases meeting all of the following requirements:

    • 1-3 de novo lesions
    • Metastases must be from a histologically confirmed extracerebral primary site, another metastatic site, or from the metastatic brain lesion(s)
    • Each lesion must be less than 3.0 cm by contrasted MRI of the brain
    • Lesions must not be within 5 mm of optic chiasm or within the brainstem
  • No primary germ cell tumor, small cell carcinoma, or lymphoma

  • No leptomeningeal metastases

  • Eligible for treatment with gamma knife or linear accelerator-based radiosurgery

  • Performance status - ECOG 0-2

  • Performance status - Zubrod 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 body

  • No known allergy to gadolinium

  • Deemed to be at low risk for recurrence from any prior malignancies

  • At least 7 days since prior chemotherapy

  • Concurrent hormonal agents allowed

  • Concurrent steroids allowed

  • No prior cranial radiotherapy

  • No prior resection of cerebral metastasis

  • Concurrent anticonvulsants allowed provided therapeutic serum/plasma level maintained before study intervention

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
radiosurgeryradiation therapyPatients undergo radiosurgery. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.
radiosurgerysurgeryPatients undergo radiosurgery. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.
radiosurgery + WBRTradiation therapyPatients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
radiosurgery + WBRTsurgeryPatients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
radiosurgery + WBRTWBRTPatients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Primary Outcome Measures
NameTimeMethod
Overall survival (OS)Up to 6 months
Secondary Outcome Measures
NameTimeMethod
Time to CNS failureUp to 4 years
Change in QOL between SRS and SRS + WBRT treatment groups using the FACT-BR questionnaireFrom baseline to up to 3 months
Change in the duration of functional independence using the Barthel ADL Index scoreFrom baseline to up to 4 years

Trial Locations

Locations (37)

Comprehensive Cancer Center at Wake Forest University

🇺🇸

Winston-Salem, North Carolina, United States

Methodist Cancer Center at Methodist University Hospital

🇺🇸

Memphis, Tennessee, United States

American Fork Hospital

🇺🇸

American Fork, Utah, United States

Massey Cancer Center at Virginia Commonwealth University

🇺🇸

Richmond, Virginia, United States

University of Wisconsin Comprehensive Cancer Center

🇺🇸

Madison, Wisconsin, United States

University of Alabama at Birmingham Comprehensive Cancer Center

🇺🇸

Birmingham, Alabama, United States

St. Joseph's Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Foundation for Cancer Research and Education

🇺🇸

Phoenix, Arizona, United States

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

University of Colorado Cancer Center at University of Colorado Health Sciences Center

🇺🇸

Aurora, Colorado, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

Duke Comprehensive Cancer Center

🇺🇸

Durham, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

Barbara Ann Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

American College of Surgeons Oncology Group

🇺🇸

Durham, North Carolina, United States

UPMC St. Margaret

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Medical College of Wisconsin Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

University of Pittsburgh Medical Center - Shadyside Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Yale Comprehensive Cancer Center

🇺🇸

New Haven, Connecticut, United States

Genesis Regional Cancer Center at Genesis Medical Center

🇺🇸

Davenport, Iowa, United States

John F. Kennedy Medical Center

🇺🇸

Edison, New Jersey, United States

SUNY Upstate Medical University Hospital

🇺🇸

Syracuse, New York, United States

John Muir Comprehensive Cancer Center at John Muir Medical Center

🇺🇸

Walnut Creek, California, United States

Shands Cancer Center at the University of Florida Health Science Center

🇺🇸

Gainesville, Florida, United States

Siteman Cancer Center at Barnes-Jewish Hospital

🇺🇸

Saint Louis, Missouri, United States

Mount Diablo Regional Cancer Center

🇺🇸

Concord, California, United States

University of Illinois Medical Center

🇺🇸

Chicago, Illinois, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Allegheny General Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Cancer Center at the University of Virginia

🇺🇸

Charlottesville, Virginia, United States

Carolina Neurosurgery and Spine Associates

🇺🇸

Charlotte, North Carolina, United States

Blumenthal Cancer Center at Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

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