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.

Condition	Treatment or Intervention	Phase
brain metastases	Procedure: radiation therapy  Procedure: stereotactic radiosurgery	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• 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

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• At least 7 days since prior chemotherapy

Endocrine therapy:

• Concurrent hormonal agents allowed
• Concurrent steroids allowed

Radiotherapy:

• See Disease Characteristics
• No prior cranial radiotherapy

Surgery:

• No prior resection of cerebral metastasis

Other:

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

Alabama
      University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham,  Alabama,  35294-3295,  United States
Arizona
      Foundation for Cancer Research and Education, Phoenix,  Arizona,  85013,  United States
      St. Joseph's Hospital and Medical Center, Phoenix,  Arizona,  85001-2071,  United States
California
      John Muir Comprehensive Cancer Center at John Muir Medical Center, Walnut Creek,  California,  94598,  United States
      Mount Diablo Regional Cancer Center, Concord,  California,  94524-4110,  United States
      Sutter Cancer Center, Sacramento,  California,  95816,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8040,  United States
Florida
      Shands Cancer Center at the University of Florida Health Science Center, Gainesville,  Florida,  32610-100277,  United States
Illinois
      University of Illinois Medical Center, Chicago,  Illinois,  60612,  United States
Iowa
      Genesis Regional Cancer Center at Genesis Medical Center, Davenport,  Iowa,  52803,  United States
Kansas
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Brigham and Women's Hospital, Boston,  Massachusetts,  02115,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States
Missouri
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
New Jersey
      John F. Kennedy Medical Center, Edison,  New Jersey,  08818,  United States
New York
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States
North Carolina
      Blumenthal Cancer Center at Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States
      Carolina Neurosurgery and Spine Associates, Charlotte,  North Carolina,  28232-2861,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States
      Penn State Cancer Institute at Milton S. Hershey Medical Center, Hershey,  Pennsylvania,  17033-0850,  United States
      University of Pittsburgh Medical Center - Shadyside Hospital, Pittsburgh,  Pennsylvania,  15213-2582,  United States
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15213,  United States
      UPMC St. Margaret, Pittsburgh,  Pennsylvania,  15215,  United States
Tennessee
      Methodist Cancer Center at Methodist University Hospital, Memphis,  Tennessee,  38104,  United States
Utah
      American Fork Hospital, American Fork,  Utah,  84003,  United States
Virginia
      Cancer Center at the University of Virginia, Charlottesville,  Virginia,  22908,  United States
      Massey Cancer Center at Virginia Commonwealth University, Richmond,  Virginia,  23298-0631,  United States
Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States
      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792-7375,  United States

Study chairs or principal investigators

Anthony Asher, MD, FACS,  Study Chair,  Carolina Neurosurgery and Spine Associates   

Study ID Numbers:  CDR0000069183; ACOSOG-Z0300
Record last reviewed:  January 2005
Last Updated:  January 12, 2005
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030628
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08