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

A Phase III Randomized Trial Of The Role Of Whole Brain Radiation Therapy In Addition To Radiosurgery In The Management Of Patients With One To Three Cerebral Metastases

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer
• Intervention / Treatment: Procedure: surgery; Radiation: radiation therapy; Radiation: WBRT

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.

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3295
      • University of Alabama at Birmingham Comprehensive Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
    • Phoenix, Arizona, United States, 85001-2071
      • St. Joseph's Hospital and Medical Center
  • California
    • Concord, California, United States, 94524-4110
      • Mount Diablo Regional Cancer Center
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Center
    • Walnut Creek, California, United States, 94598
      • John Muir Comprehensive Cancer Center at John Muir Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8040
      • Yale Comprehensive Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610-100277
      • Shands Cancer Center at the University of Florida Health Science Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center
  • Iowa
    • Davenport, Iowa, United States, 52803
      • Genesis Regional Cancer Center at Genesis Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • New Jersey
    • Edison, New Jersey, United States, 08818
      • John F. Kennedy Medical Center
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28232-2861
      • Carolina Neurosurgery and Spine Associates
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Durham, North Carolina, United States, 27705
      • American College of Surgeons Oncology Group
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center at Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15215
      • UPMC St. Margaret
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • University of Pittsburgh Medical Center - Shadyside Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Methodist Cancer Center at Methodist University Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Cancer Center at the University of Virginia
    • Richmond, Virginia, United States, 23298-0631
      • Massey Cancer Center at Virginia Commonwealth University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-7375
      • University of Wisconsin Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: radiosurgery; Patients 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.	Procedure: surgery; Radiation: radiation therapy
Experimental: radiosurgery + WBRT; 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.	Procedure: surgery; Radiation: radiation therapy; Radiation: WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to CNS failure	Up to 4 years
Change in QOL between SRS and SRS + WBRT treatment groups using the FACT-BR questionnaire	From baseline to up to 3 months
Change in the duration of functional independence using the Barthel ADL Index score	From baseline to up to 4 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Anthony Asher, MD, FACS, Carolina Neurosurgery and Spine Associates

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Primary Completion (Actual): March 1, 2005
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 7, 2016
• Last Update Submitted That Met QC Criteria: July 6, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: tumors metastatic to brain
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: ACOSOG-Z0300; CDR0000069183 (Other Identifier: NCI Physician Data Query)