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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00377156
• Other study ID #: N0574
• Secondary ID: NCCTG-N0574ACOSO
• Status: Completed
• Phase: Phase 3
• Start date: July 2006
• Est. completion date: December 15, 2019

Study information

• Verified date: September 2022
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: December 15, 2019
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cognitive/Functional Effects
• Lung Cancer
• Lung Neoplasms
• Metastatic Cancer
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• radiation therapy
Patients undergo radiation therapy 5 days a week for 2.5 weeks
• stereotactic radiosurgery

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	CHUS-Hopital Fleurimont	Sherbrooke	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Northwest Community Hospital	Arlington Heights	Illinois
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Billings Clinic - Downtown	Billings	Montana
United States	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire
United States	CCOP - Duluth	Duluth	Minnesota
United States	Cape Fear Valley Medical Center Cancer Center	Fayetteville	North Carolina
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Greenville Cancer Center of the Carolinas (CCOP)	Greenville	South Carolina
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Lowell General Hospital	Lowell	Massachusetts
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Memorial Medical Center	Modesto	California
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Kaiser Permanente - Division of Research - Oakland	Oakland	California
United States	Immanuel Medical Center	Omaha	Nebraska
United States	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Owensboro Mercy Medical Center	Owensboro	Kentucky
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	Arizona Oncology-Deer Valley Center	Phoenix	Arizona
United States	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California
United States	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Arizona Oncology Services Foundation	Scottsdale	Arizona
United States	Somerset Medical Center	Somerville	New Jersey
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Legacy Salmon Creek Medical Center	Vancouver	Washington
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Coastal Carolina Radiation Oncology Center	Wilmington	North Carolina
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina
United States	Cancer Treatment Center	Wooster	Ohio
United States	Saint Vincent Hospital at Worcester Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months	The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.	3 months post radiosurgery
Secondary	Number of Participants With Local and Distant Tumor Control up to 3 Months	Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....	Up to 3 months
Secondary	Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]	Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.	From Baseline to 3-Month Evaluation
Secondary	Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months	Long-Term Neurocognitive Status > To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.	From baseline to 12 months
Secondary	Overall Survival	Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.	Up to 5 years

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive