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

• ClinicalTrials.gov Identifier: NCT00377156
• Recruitment Status: Completed
• First Posted: September 15, 2006
• Results First Posted: August 24, 2017
• Last Update Posted: February 12, 2020
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Cognitive/Functional Effects; Lung Cancer; Metastatic Cancer; Prostate Cancer	Radiation: radiation therapy; Radiation: stereotactic radiosurgery	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 2006
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: December 15, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm I; Patients undergo stereotactic radiosurgery (SRS)	Radiation: stereotactic radiosurgery
Experimental: 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.	Radiation: radiation therapy; Patients undergo radiation therapy 5 days a week for 2.5 weeks; Radiation: stereotactic radiosurgery

Outcome Measures

Primary Outcome Measures :

1. Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months [ Time Frame: 3 months post radiosurgery ]
   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.

Secondary Outcome Measures :

1. Number of Participants With Local and Distant Tumor Control up to 3 Months [ Time Frame: Up to 3 months ]
   Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....
2. Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month] [ Time Frame: From Baseline to 3-Month Evaluation ]
   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.
3. Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months [ Time Frame: From baseline to 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.
4. Overall Survival [ Time Frame: Up to 5 years ]
   Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology-Deer Valley Center

Phoenix, Arizona, United States, 85027

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States, 85260

United States, California

Memorial Medical Center

Modesto, California, United States, 95355

Kaiser Permanente - Division of Research - Oakland

Oakland, California, United States, 94611

St. Joseph Hospital Regional Cancer Center - Orange

Orange, California, United States, 92868

Rohnert Park Cancer Center

Rohnert Park, California, United States, 94928

Kaiser Permanente Medical Center - Santa Clara Kiely Campus

Santa Clara, California, United States, 95051

Kaiser Permanente Medical Center - Santa Rosa

Santa Rosa, California, United States, 95403

United States, Colorado

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, United States, 80045

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States, 80220

United States, Florida

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States, 32224

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States, 32803-1273

United States, Georgia

Northside Hospital Cancer Center

Atlanta, Georgia, United States, 30342-1611

Saint Joseph's Hospital of Atlanta

Atlanta, Georgia, United States, 30342-1701

Northeast Georgia Medical Center

Gainesville, Georgia, United States, 30501

Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler

Savannah, Georgia, United States, 31405

United States, Idaho

Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center

Boise, Idaho, United States, 83706

United States, Illinois

Northwest Community Hospital

Arlington Heights, Illinois, United States, 60005

United States, Kansas

Via Christi Cancer Center at Via Christi Regional Medical Center

Wichita, Kansas, United States, 67214

United States, Kentucky

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, United States, 40536-0093

Owensboro Mercy Medical Center

Owensboro, Kentucky, United States, 42303

United States, Louisiana

Ochsner Cancer Institute at Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

United States, Massachusetts

Lowell General Hospital

Lowell, Massachusetts, United States, 01854

Saint Vincent Hospital at Worcester Medical Center

Worcester, Massachusetts, United States, 01608

United States, Michigan

Henry Ford Hospital

Detroit, Michigan, United States, 48202

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States, 48202

West Michigan Cancer Center

Kalamazoo, Michigan, United States, 49007-3731

United States, Minnesota

CCOP - Duluth

Duluth, Minnesota, United States, 55805

Mayo Clinic Cancer Center

Rochester, Minnesota, United States, 55905

CentraCare Clinic - River Campus

Saint Cloud, Minnesota, United States, 56303

United States, Missouri

Cancer Institute of Cape Girardeau, LLC

Cape Girardeau, Missouri, United States, 63703

Saint Luke's Cancer Institute at Saint Luke's Hospital

Kansas City, Missouri, United States, 64111

United States, Montana

Billings Clinic - Downtown

Billings, Montana, United States, 59107-7000

United States, Nebraska

Immanuel Medical Center

Omaha, Nebraska, United States, 68122

United States, New Hampshire

Seacoast Cancer Center at Wentworth - Douglass Hospital

Dover, New Hampshire, United States, 03820

Elliot Regional Cancer Center at Elliot Hospital

Manchester, New Hampshire, United States, 03103

United States, New Jersey

Somerset Medical Center

Somerville, New Jersey, United States, 08876

J. Phillip Citta Regional Cancer Center at Community Medical Center

Toms River, New Jersey, United States, 08755

United States, North Carolina

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States, 28203

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States, 28232-2861

Cape Fear Valley Medical Center Cancer Center

Fayetteville, North Carolina, United States, 28302-2000

Coastal Carolina Radiation Oncology Center

Wilmington, North Carolina, United States, 28401

Forsyth Regional Cancer Center at Forsyth Medical Center

Winston-Salem, North Carolina, United States, 27103

United States, North Dakota

Medcenter One Hospital Cancer Care Center

Bismarck, North Dakota, United States, 58501

Sanford Bismarck Medical Center

Bismarck, North Dakota, United States, 58501

United States, Ohio

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, United States, 44309-2090

Cancer Care Center, Incorporated

Salem, Ohio, United States, 44460

Cancer Treatment Center

Wooster, Ohio, United States, 44691

United States, Oregon

Legacy Mount Hood Medical Center

Gresham, Oregon, United States, 97030

Legacy Good Samaritan Hospital & Comprehensive Cancer Center

Portland, Oregon, United States, 97210

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, United States, 97210

United States, Pennsylvania

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, United States, 17822-0001

Frankford Hospital Cancer Center - Torresdale Campus

Philadelphia, Pennsylvania, United States, 19114

United States, South Carolina

Cancer Centers of the Carolinas - Faris Road

Greenville, South Carolina, United States, 29605

CCOP - Greenville

Greenville, South Carolina, United States, 29615

Greenville Cancer Center of the Carolinas (CCOP)

Greenville, South Carolina, United States, 29615

United States, Texas

University of Texas Medical Branch

Galveston, Texas, United States, 77555

United States, Washington

Legacy Salmon Creek Medical Center

Vancouver, Washington, United States, 98686

United States, Wisconsin

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States, 54307-3508

All Saints Cancer Center at Wheaton Franciscan Healthcare

Racine, Wisconsin, United States, 53405

Canada, Alberta

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada, T2N 4N2

Canada, Ontario

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, Canada, L8V 5C2

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, Canada, J1H 5N4

Sponsors and Collaborators

Alliance for Clinical Trials in Oncology

National Cancer Institute (NCI)

Investigators

• Study Chair: Paul D. Brown, MD; Mayo Clinic

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Ménard 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.

Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Ménard 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. Erratum in: JAMA. 2018 Aug 7;320(5):510.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00377156
• Other Study ID Numbers: N0574; NCCTG-N0574; ACOSOG-N0574; CDR0000499633 ( Registry Identifier: PDQ (Physician Data Query) ); NCI-2009-00653 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
• First Posted: September 15, 2006
• Results First Posted: August 24, 2017
• Last Update Posted: February 12, 2020
• Last Verified: February 2020

Keywords provided by Alliance for Clinical Trials in Oncology:

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

Additional relevant MeSH terms:

Breast Neoplasms; Lung Neoplasms; Prostatic Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Prostatic Diseases