Clinical trial NCT00030628: Radiosurgery With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Cancer
Keywords: tumors metastatic to brain
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Time to CNS failure
timeFrame: Up to 4 years
measure: Change in QOL between SRS and SRS + WBRT treatment groups using the FACT-BR questionnaire
timeFrame: From baseline to up to 3 months
measure: Change in the duration of functional independence using the Barthel ADL Index score
timeFrame: From baseline to up to 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Foundation for Cancer Research and Education
state: Arizona
city: Concord
country: United States
facility: Mount Diablo Regional Cancer Center
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Walnut Creek
country: United States
facility: John Muir Comprehensive Cancer Center at John Muir Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: New Haven
country: United States
facility: Yale Comprehensive Cancer Center
state: Connecticut
city: Gainesville
country: United States
facility: Shands Cancer Center at the University of Florida Health Science Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois Medical Center
state: Illinois
city: Davenport
country: United States
facility: Genesis Regional Cancer Center at Genesis Medical Center
state: Iowa
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Edison
country: United States
facility: John F. Kennedy Medical Center
state: New Jersey
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolina Neurosurgery and Spine Associates
state: North Carolina
city: Durham
country: United States
facility: American College of Surgeons Oncology Group
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Shadyside Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC St. Margaret
state: Pennsylvania
city: Memphis
country: United States
facility: Methodist Cancer Center at Methodist University Hospital
state: Tennessee
city: American Fork
country: United States
facility: American Fork Hospital
state: Utah
city: Charlottesville
country: United States
facility: Cancer Center at the University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center at Virginia Commonwealth University
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Carolina Neurosurgery and Spine Associates
name: Anthony Asher, MD, FACS
role: STUDY_CHAIR
References: