Stereotactic Radiosurgery or Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases That Have Been Removed By Surgery

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive18 and overNCI, OtherN107C
NCCTG-N107C, CDR0000701474, NCI-2011-02676, NCT01372774

Trial Description

Summary

RATIONALE: Stereotactic radiosurgery may be able to 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 radiosurgery is more effective than whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery.

PURPOSE: This randomized phase III trial studies how well stereotactic radiosurgery works compared to whole-brain radiation therapy in treating patients with brain metastases that have been removed by surgery.

Further Study Information

OBJECTIVES:

Primary

  • To ascertain in patients with one to four brain metastases whether there is improved overall survival in patients who receive stereotactic radiosurgery (SRS) to the surgical bed compared to patients who receive whole-brain radiotherapy (WBRT).
  • To ascertain in patients with one to four brain metastases whether there is less neurocognitive progression at 6 months post-radiation in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

Secondary

  • To ascertain in patients with resected brain metastases whether there is improved quality-of-life (QOL) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  • To ascertain in patients with one to four brain metastases whether there is equal longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  • To ascertain in patients with one to four brain metastases whether there is longer duration of functional independence in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  • To ascertain in patients with one to four brain metastases whether there is better long-term neurocognitive status in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
  • To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
  • To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.
  • To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.
  • To evaluate if there is any difference in CNS failure patterns (local, distant, leptomeningeal) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

Exploratory

  • To evaluate radiation changes in the limbic system that may correlate with neurotoxicity using brain MRI scans.
  • To determine whether Apo E (i.e., Apo E2, Apo E3, and Apo E4) genotyping may prove to be a predictor of radiation-induced neurocognitive decline (or neuroprotection).
  • To determine whether inflammatory markers (i.e., IL-1, IL-6, and TNF-α) may prove to be predictors of radiation-induced neurocognitive decline.
  • To determine whether oxidative stress biomarkers (i.e., protein carbonyl content, lipid hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced neurocognitive decline.
  • To determine whether hormone and growth factors [i.e., glucocorticoids (e.g., cortisol), gonadal steroids (e.g., estradiol, testosterone, progesterone), growth hormone, human chorionic gonadotropin (hCG), insulin-like growth factor-1 (IGF-1), and neuronal growth factor (NGF)] may prove to be a predictor of radiation-induced neurocognitive decline.

OUTLINE: This is a multicenter study. Patients are stratified according to age in years (< 60 vs ≥ 60), extracranial disease controlled (≤ 3 months vs > 3 months), number of pre-operative brain metastases (1 vs 2-4), histology (lung vs radioresistant [brain metastases from a sarcoma, melanoma, or renal cell carcinoma histology] vs other), and resection cavity maximal diameter (≤ 3 cm vs > 3 cm). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo whole-brain radiotherapy (WBRT) once a day, 5 days a week, for approximately 3 weeks.
  • Arm II: Patients undergo stereotactic radiosurgery (SRS) using a gamma knife or a linear accelerator procedure.

Serum, whole blood, and urine samples are collected at baseline and periodically during study for genetic markers, inflammatory markers, oxidative stress biomarkers, and hormone and growth factor studies by ELISA and other assays.

Patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR), the activities of daily living (ADLs), the Fatigue/Uniscale Assessment, and the Linear Analog Self Assessment (LASA) quality-of-life questionnaires at baseline and periodically during study. Neurocognitive functions, such as memory, verbal fluency, visual attention, executive function, and delayed memory, are also assessed.

After completion of study therapy, patients are followed up periodically for 5 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

  • Four or fewer brain metastases (as defined on the pre-operative MRI brain scan) and status post resection of one of the lesions
  • Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site
  • Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site
  • Any unresected lesions must measure ≤ 3.0 cm in maximal extent on the contrasted MRI brain scan obtained ≤ 35 days prior to pre-registration
  • The metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility
  • Post-operative MRI confirmed zero, one, two or three unresected lesions
  • Each unresected lesion must measure ≤ 3.0 cm in maximal extent on the contrasted post-operative MRI brain scan
  • The pre-registration, post-operative, brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization
  • Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤ 28 days prior to randomization
  • Resection cavity must measure < 5.0 cm in maximal extent on the post-operative MRI (or CT) brain scan obtained ≤ 35 days prior to pre-registration
  • The pre-registration, post-operative brain scan may be used for the planning scan if obtained ≤ 28 days prior to randomization
  • Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤ 28 days prior to randomization
  • It is permissible for the resection of a dominant brain metastasis to include a smaller "satellite" metastasis as long as the single resection cavity is less than the maximum size requirements
  • All standard tumor-staging procedures necessary to define baseline extracranial disease status completed ≤ 42 days prior to pre-registration
  • No primary germ cell tumor, small cell carcinoma, or lymphoma
  • No widespread definitive leptomeningeal metastasis
  • No brain metastasis that is located ≤ 5 mm of the optic chiasm or within the brainstem

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0, 1, or 2
  • Ability to be treated with either a gamma knife or a linear accelerator-based radiosurgery system
  • Willing and able to complete neurocognitive examination without assistance
  • Willing and able to complete quality-of-life (QOL) questionnaires by themselves or with assistance
  • Willing to provide mandatory blood and urine samples for correlative research purposes
  • None of the following:
  • Pregnant or nursing
  • Men or women of childbearing potential who are unwilling to employ adequate contraception through out the study and for men for up to 3 months after completing treatment
  • Able to complete a MRI with contrast of the head
  • No known allergy to gadolinium

PRIOR CONCURRENT THERAPY:

  • No prior cranial radiotherapy
  • No planned cytotoxic chemotherapy during the stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT)
  • Concurrent hormonal agents, steroids, and/or anticonvulsants allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

North Central Cancer Treatment Group

  • National Cancer Institute
Paul D. Brown, Principal Investigator

Trial Sites

U.S.A.

California
Burlingame

Peninsula Medical Center

Milana V Dolezal
Ph: 415-209-2686
Email: bernicl@sutterhealth.org

Los Angeles

USC/Norris Comprehensive Cancer Center and Hospital

Eric L Chang
Ph: 323-865-0451

Eric L Chang
Ph: 323-865-0451

Modesto

Memorial Medical Center

Jorge A Garcia-Young
Ph: 415-209-2686
Email: bernicl@sutterhealth.org

Vallejo

Sutter Solano Medical Center

Milana V Dolezal
Ph: 415-209-2686
Email: bernicl@sutterhealth.org

Colorado
Englewood

Swedish Medical Center

Keren Sturtz
Ph: 888-785-6789

Pueblo

St. Mary - Corwin Regional Medical Center

Keren Sturtz
Ph: 888-785-6789

Connecticut
New Britain

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus

Neal B Goldberg
Ph: 860-224-5660

Delaware
Newark

Helen F. Graham Cancer Center at Christiana Hospital

Sunjay A Shah
Ph: 302-733-6227

Sunjay A Shah
Ph: 302-733-6227

Florida
Hollywood

Joe DiMaggio Children's Hospital

Srinath Sundararaman
Ph: 954-265-2234

Miami

University of Miami Sylvester Comprehensive Cancer Center - Miami

Fazilat Ishkanian
Ph: 866-574-5124
Email: Sylvester@emergingmed.com

Miami Beach

CCOP - Mount Sinai Medical Center

Michael Schwartz
Ph: 305-674-2625
Email: info@msccop.com

Orlando

M.D. Anderson Cancer Center at Orlando

Naren R Ramakrishna
Ph: 321-841-7246
Email: CancerClinicalTrials@orlandohealth.com

Pembroke Pines

Memorial Cancer Institute at Memorial Hospital West

Srinath Sundararaman
Ph: 954-265-2234

Georgia
Columbus

John B. Amos Cancer Center

Douglas F. Ciuba
Ph: 706-660-6404

Idaho
Post Falls

Kootenai Cancer Center - Post Falls

Benjamin Thomas Marchello
Ph: 800-648-6274

Illinois
Chicago

University of Illinois Cancer Center

Matthew Koshy
Ph: 312-355-3046

Evanston

CCOP - Evanston

Ryan T Merrell
Ph: 847-570-2109

Peoria

OSF St. Francis Medical Center

Nguyet A Le-Lindqwister
Ph: 800-793-2262

Indiana
South Bend

Memorial Hospital of South Bend

David A. Hornback
Ph: 800-284-7370

Iowa
Cedar Rapids

Mercy Regional Cancer Center at Mercy Medical Center

Deborah W Wilbur
Ph: 319-363-2690

Des Moines

John Stoddard Cancer Center at Iowa Methodist Medical Center

Robert J Behrens
Ph: 515-282-2921

Kansas
Kansas City

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Parvesh Kumar
Ph: 913-588-4709

Overland Park

Kansas City Cancer Centers - Southwest

Parvesh Kumar
Ph: 913-588-4709

Kentucky
Lexington

University of Kentucky Chandler Medical Center

John L Villano
Ph: 859-257-3379

Louisville

Louisville Oncology at Norton Cancer Institute - Louisville

Aaron C Spalding
Ph: 502-629-2500

Maine
Portland

Maine Medical Center - Bramhall Campus

Ian J Bristol
Ph: 207-396-8090
Email: wrighd@mmc.org

Maryland
Baltimore

Greater Baltimore Medical Center Cancer Center

Geoffrey A Neuner
Ph: 443-849-3706

Rockville

Cancer Trials Support Unit

Paul D. Brown

Massachusetts
Lowell

Lowell General Hospital

Matthew S Katz
Ph: 978-788-7084
Email: ghincks@lowellgeneral.org

Worcester

Saint Vincent Hospital - Fallon Clinic

William B Casey
Ph: 508-363-7018

Michigan
Kalamazoo

West Michigan Cancer Center

Sunil Nagpal
Ph: 269-373-7458

Minnesota
Bemidji

MeritCare Bemidji

Preston D. Steen
Ph: 701-234-6161

Rochester

Mayo Clinic Cancer Center

Nadia N Laack
Ph: 507-538-7623

Saint Cloud

CentraCare Clinic - Women and Children

Donald J Jurgens
Ph: 877-229-4907
Email: coborncancercenter@centracare.com

Saint Paul

Regions Hospital Cancer Care Center

Patrick J. Flynn
Ph: 952-993-1517
Email: MMCCOP@parknicollet.com

United Hospital

Patrick J. Flynn
Ph: 952-993-1517
Email: MMCCOP@parknicollet.com

Montana
Billings

Billings Clinic Cancer Center - 801 N 29th Street

Benjamin Thomas Marchello
Ph: 800-648-6274

CCOP - Montana Cancer Consortium

Paul D. Brown

Nebraska
Omaha

Fred and Pamela Buffett Cancer Center

Andrew O Wahl
Ph: 402-559-6941
Email: unmcrsa@unmc.edu

New Hampshire
Dover

Seacoast Cancer Center at Wentworth - Douglass Hospital

Arul Mahadevan
Ph: 603-740-2150

Exeter

Center for Cancer Care at Exeter Hospital

Gary Miller Proulx
Ph: 800-439-3837

New Jersey
Somerville

Somerset Medical Center

Joel K Braver
Ph: 908-685-2481

New York
Syracuse

SUNY Upstate Medical University Hospital

Seung Shin Hahn
Ph: 315-464-5476

North Carolina
Chapel Hill

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Timothy M Zagar
Ph: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu

Greenville

Leo W. Jenkins Cancer Center at ECU Medical School

Clinton H Leinweber
Ph: 252-744-2391

North Dakota
Bismarck

Medcenter One Hospital Cancer Care Center

Preston D. Steen
Ph: 701-234-6161

Fargo

Roger Maris Cancer Center at MeritCare Hospital

Preston D. Steen
Ph: 701-234-6161

Sanford Clinic North-Fargo

Preston D. Steen
Ph: 701-234-6161

Ohio
Akron

Summa Center for Cancer Care at Akron City Hospital

Charles A Kunos
Ph: 330-375-6101

Cleveland

Case Comprehensive Cancer Center

Min Yao
Ph: 800-641-2422

Cleveland Clinic Taussig Cancer Center

Samuel T Chao
Ph: 866-223-8100

Westerville

Mount Carmel St. Ann's Cancer Center

J. Philip Kuebler
Ph: 614-566-3275

Oklahoma
Oklahoma City

Stephenson Cancer Center at the University of Oklahoma

Terence S. Herman
Ph: 405-271-4272
Email: julie-traylor@ouhsc.edu

Oregon
Portland

Legacy Good Samaritan Hospital & Comprehensive Cancer Center

Andrew Y Kee
Ph: 507-538-7623

Pennsylvania
Abington

Rosenfeld Cancer Center at Abington Memorial Hospital

Wayne H Pinover
Ph: 215-481-2402

Danville

Geisinger Cancer Institute at Geisinger Health

Thomas J Gergel
Ph: 570-271-5251

Philadelphia

Frankford Hospital Cancer Center - Torresdale Campus

Voichita Bar Ad
Ph: 215-955-6084

South Dakota
Rapid City

Rapid City Regional Hospital

Joshua C Lukenbill
Ph: 605-716-3982
Email: research@rcrh.org

Sioux Falls

Sanford Cancer Center at Sanford USD Medical Center

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Ph: 701-234-6161

Tennessee
Knoxville

Thompson Cancer Survival Center

Joseph Thurmond Meyer
Ph: 865-541-1812

Nashville

Vanderbilt-Ingram Cancer Center

Albert Attia
Ph: 800-811-8480

Texas
Galveston

University of Texas Medical Branch

Todd A Swanson
Ph: 409-772-1950
Email: clinical.research@utmb.edu

Utah
Murray

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

R. Jeffrey Lee
Ph: 801-507-3950

Saint George

Dixie Regional Medical Center - East Campus

R. Jeffrey Lee
Ph: 801-507-3950

Salt Lake City

Huntsman Cancer Institute at University of Utah

Dennis C. Shrieve
Ph: 801-581-4477
Email: clinical.trials@hci.utah.edu

Wisconsin
Green Bay

St. Vincent Hospital Regional Cancer Center

Anthony J. Jaslowski
Ph: 800-432-6049

Milwaukee

Froedtert Hospital and Medical College of Wisconsin

Joseph A Bovi
Ph: 414-805-4380

Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center

Mitchell H. Pincus
Ph: 800-252-2990

Waukesha

Waukesha Memorial Hospital Regional Cancer Center

Timothy R Wassenaar
Ph: 262-928-7878

Canada

Nova Scotia
Halifax

Nova Scotia Cancer Centre

Liam A Mulroy
Ph: 902-473-6000

Ontario
Hamilton

Margaret and Charles Juravinski Cancer Centre

Anthony C Whitton
Ph: 905-387-9495

Toronto

Princess Margaret Hospital

Normand J Laperriere
Ph: 416-946-4501
Email: clinical.trials@uhn.on.ca

Quebec
Montreal

Hopital Notre-Dame du CHUM

David Roberge
Ph: 514-890-8000ext23611
Email: sylvie.beaudoin.chum@ssss.gouv.qc.ca

Quebec City

Centre Hospitalier Universitaire de Quebec

Melanie Gaudreault
Ph: 418-525-4444

Sherbrooke

CHUS-Hopital Fleurimont

Laurence Masson-Cote
Ph: 819-820-6480
Email: crcinformation.chus@ssss.gouv.qc.ca

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01372774
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.