Clinical trial NCT00377156: Stereotactic Radiation Therapy With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
Official title: Phase III Randomized Trial of the Role of Whole Brain Radiation Therapy in Addition to Radiosurgery in Patients With One to Three Cerebral Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Cognitive/Functional Effects
Lung Cancer
Metastatic Cancer
Prostate Cancer
Keywords: cognitive/functional effects
tumors metastatic to brain
stage IV breast cancer
stage IV prostate cancer
stage IV non-small cell lung cancer
male breast cancer
recurrent breast cancer
recurrent prostate cancer
recurrent non-small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-09-15
Enrollment: 213
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: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months
timeFrame: 3 months post radiosurgery
Secondary outcomes:
measure: Number of Participants With Local and Distant Tumor Control up to 3 Months
timeFrame: Up to 3 months
measure: Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]
timeFrame: From Baseline to 3-Month Evaluation
measure: Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months
timeFrame: From baseline to 12 months
measure: Overall Survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology-Deer Valley Center
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Modesto
country: United States
facility: Memorial Medical Center
state: California
city: Oakland
country: United States
facility: Kaiser Permanente - Division of Research - Oakland
state: California
city: Orange
country: United States
facility: St. Joseph Hospital Regional Cancer Center - Orange
state: California
city: Rohnert Park
country: United States
facility: Rohnert Park Cancer Center
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Medical Center - Santa Clara Kiely Campus
state: California
city: Santa Rosa
country: United States
facility: Kaiser Permanente Medical Center - Santa Rosa
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital Cancer Center
state: Georgia
city: Atlanta
country: United States
facility: Saint Joseph's Hospital of Atlanta
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Savannah
country: United States
facility: Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
state: Idaho
city: Arlington Heights
country: United States
facility: Northwest Community Hospital
state: Illinois
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Owensboro
country: United States
facility: Owensboro Mercy Medical Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Cancer Institute at Ochsner Clinic Foundation
state: Louisiana
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: Saint Vincent Hospital at Worcester Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Cape Girardeau
country: United States
facility: Cancer Institute of Cape Girardeau, LLC
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute at Saint Luke's Hospital
state: Missouri
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Dover
country: United States
facility: Seacoast Cancer Center at Wentworth - Douglass Hospital
state: New Hampshire
city: Manchester
country: United States
facility: Elliot Regional Cancer Center at Elliot Hospital
state: New Hampshire
city: Somerville
country: United States
facility: Somerset Medical Center
state: New Jersey
city: Toms River
country: United States
facility: J. Phillip Citta Regional Cancer Center at Community Medical Center
state: New Jersey
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Medical Center Cancer Center
state: North Carolina
city: Wilmington
country: United States
facility: Coastal Carolina Radiation Oncology Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Regional Cancer Center at Forsyth Medical Center
state: North Carolina
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Comprehensive Cancer Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: Frankford Hospital Cancer Center - Torresdale Campus
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Faris Road
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Center of the Carolinas (CCOP)
state: South Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Vancouver
country: United States
facility: Legacy Salmon Creek Medical Center
state: Washington
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Racine
country: United States
facility: All Saints Cancer Center at Wheaton Franciscan Healthcare
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Sherbrooke
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
Study officials:
affiliation: Mayo Clinic
name: Paul D. Brown, MD
role: STUDY_CHAIR
References:
citation: Churilla TM, Ballman KV, Brown PD, Twohy EL, Jaeckle K, Farace E, Cerhan JH, Anderson SK, Carrero XW, Garces YI, Barker FG 2nd, Deming R, Dixon JG, Burri SH, Chung C, Menard C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Stereotactic Radiosurgery With or Without Whole-Brain Radiation Therapy for Limited Brain Metastases: A Secondary Analysis of the North Central Cancer Treatment Group N0574 (Alliance) Randomized Controlled Trial. Int J Radiat Oncol Biol Phys. 2017 Dec 1;99(5):1173-1178. doi: 10.1016/j.ijrobp.2017.07.045. Epub 2017 Aug 5.
citation: Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.