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

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Treatment18 and overN107C
NCI-2011-02676, CDR0000701474, NCCTG-N107C, NCT01372774

Trial Description

Summary

This randomized phase III trial studies stereotactic radiosurgery to see how well it works compared to whole-brain radiation therapy in treating patients with cancer that has spread to the brain from the original tumor and that has been removed by surgery. 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.

Further Study Information

PRIMARY OBJECTIVES:

I. To determine 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).

II. To determine in patients with one to four brain metastases whether there is less neurocognitive progression post-randomization in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

SECONDARY OBJECTIVES:

I. To determine 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.

II. To determine in patients with one to four brain metastases whether there is equal or longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.

III. To determine 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.

IV. To determine 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.

V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.

VI. To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.

VII. To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.

VIII. 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.

TERTIARY OBJECTIVES:

I. To evaluate radiation changes in the limbic system that may correlate with neurotoxicity using brain magnetic resonance imaging (MRI) or computed tomography (CT) scans.

II. To determine if apolipoprotein (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).

III. To determine if inflammatory markers (i.e., interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) may prove to be predictors of radiation-induced neurocognitive decline.

XII. To determine if oxidative stress biomarkers (i.e., protein carbonyl content, lipid hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced neurocognitive decline.

XIII. To determine if 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: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo WBRT once daily (QD), 5 days a week, for approximately 3 weeks.

ARM II: Patients undergo SRS using a gamma knife or a linear accelerator procedure.

After completion of study therapy, patients are followed up at 12 weeks and then 6, 9, 12, 16, and 24 months.

Eligibility Criteria

Inclusion Criteria:

Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system

Provide written informed consent

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; Note: 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

Willing to provide mandatory blood and urine samples for correlative research purposes

Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site; Note: 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 or CT brain scan obtained =< 35 days prior to pre-registration; the unresected lesions will be treated with SRS; Note: the metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility

Willing and able to complete neurocognitive examination without assistance from family and companions; Note: because neurocognitive testing is one of the primary goals of this study, patients must be able to utilize English language booklets (and/or French booklets if enrolled in Canada)

Willing and able to complete quality-of-life (QOL) questionnaires by themselves or with assistance

Four or fewer brain metastases (as defined on the pre-operative MRI or CT brain scan) and status post resection of one of the lesions

Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

Negative urine or serum pregnancy test done =< 7 days prior to randomization, for women of child bearing potential only

Exclusion Criteria:

Planned cytotoxic chemotherapy during the SRS or WBRT

Brain metastasis that is located =< 5 mm of the optic chiasm or within the brainstem

Known allergy to gadolinium

Inability to complete a MRI or CT scan with contrast of the head

Primary germ cell tumor, small cell carcinoma, or lymphoma

Widespread definitive leptomeningeal metastasis

Prior cranial radiotherapy

Any of the following:

Pregnant women

Nursing women

Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Alliance for Clinical Trials in Oncology

  • National Cancer Institute
Paul D. Brown, Principal Investigator

Trial Sites

U.S.A.

Arizona
Phoenix

Arizona Oncology-Deer Valley Center

David G. Brachman
Ph: 877-602-4111

David G. Brachman
Principal Investigator

California
Burlingame

Mills - Peninsula Hospitals

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

Milana V. Dolezal
Principal Investigator

Los Angeles

Los Angeles County-USC Medical Center

Eric Lin Chang
Ph: 323-865-0451

Eric Lin Chang
Principal Investigator

USC / Norris Comprehensive Cancer Center

Eric Lin Chang
Ph: 323-865-0451

Eric Lin Chang
Principal Investigator

Modesto

Memorial Medical Center

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

Milana V. Dolezal
Principal Investigator

Vallejo

Sutter Solano Medical Center/Cancer Center

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

Milana V. Dolezal
Principal Investigator

Colorado
Englewood

Swedish Medical Center

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator

Pueblo

Saint Mary Corwin Medical Center

Keren Sturtz
Ph: 888-785-6789

Keren Sturtz
Principal Investigator

Connecticut
New Britain

The Hospital of Central Connecticut

Neal B. Goldberg
Ph: 860-224-5660

Neal B. Goldberg
Principal Investigator

Delaware
Newark

Christiana Care Health System-Christiana Hospital

Sunjay A. Shah
Ph: 302-733-6227

Sunjay A. Shah
Principal Investigator

Helen F Graham Cancer Center

Sunjay A. Shah
Ph: 302-733-6227

Sunjay A. Shah
Principal Investigator

Florida
Hollywood

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Srinath Sundararaman
Ph: 954-265-2234

Srinath Sundararaman
Principal Investigator

Miami

University of Miami Miller School of Medicine-Sylvester Cancer Center

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

Fazilat Ishkanian
Principal Investigator

Miami Beach

Mount Sinai Medical Center

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

Michael A. Schwartz
Principal Investigator

Orlando

UF Cancer Center at Orlando Health

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

Naren Raj Ramakrishna
Principal Investigator

Pembroke Pines

Memorial Hospital West

Srinath Sundararaman
Ph: 954-265-2234

Srinath Sundararaman
Principal Investigator

Georgia
Columbus

John B Amos Cancer Center

Douglas F. Ciuba
Ph: 706-660-6404

Douglas F. Ciuba
Principal Investigator

Idaho
Post Falls

Kootenai Cancer Center

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Illinois
Evanston

NorthShore University HealthSystem-Evanston Hospital

Ryan Thomas Merrell
Ph: 847-570-2109

Ryan Thomas Merrell
Principal Investigator

Peoria

OSF Saint Francis Medical Center

James Lloyd Wade
Ph: 217-876-4740
Email: kcheek@dmhhs.org

James Lloyd Wade
Principal Investigator

Indiana
South Bend

Memorial Hospital of South Bend

David Alan Hornback
Ph: 800-284-7370

David Alan Hornback
Principal Investigator

Iowa
Cedar Rapids

Mercy Hospital

Deborah Weil Wilbur
Ph: 319-363-2690

Deborah Weil Wilbur
Principal Investigator

Des Moines

Iowa Methodist Medical Center

Robert J. Behrens
Ph: 515-282-2921

Robert J. Behrens
Principal Investigator

Kansas
Kansas City

University of Kansas Cancer Center

Parvesh Kumar
Ph: 913-945-7552
Email: ctnursenav@kumc.edu

Parvesh Kumar
Principal Investigator

Overland Park

Kansas City Cancer Centers-Southwest

Parvesh Kumar
Ph: 913-945-7552
Email: ctnursenav@kumc.edu

Parvesh Kumar
Principal Investigator

Kentucky
Lexington

University of Kentucky/Markey Cancer Center

John Lee Villano
Ph: 859-257-3379

John Lee Villano
Principal Investigator

Louisville

Norton Hospital Pavilion and Medical Campus

Aaron C. Spalding
Ph: 502-629-2500

Aaron C. Spalding
Principal Investigator

Maine
Portland

Maine Medical Center-Bramhall Campus

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

Ian Jared Bristol
Principal Investigator

Maryland
Baltimore

Greater Baltimore Medical Center

Geoffrey Alexander Neuner
Ph: 443-849-3706

Geoffrey Alexander Neuner
Principal Investigator

Rockville

Cancer Trials Support Unit

Paul D. Brown

Paul D. Brown
Principal Investigator

Massachusetts
Lowell

Lowell General Hospital

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

Matthew Strauss Katz
Principal Investigator

Worcester

Saint Vincent Hospital/Reliant Medical Group

William B. Casey
Ph: 508-363-7018

William B. Casey
Principal Investigator

Michigan
Kalamazoo

West Michigan Cancer Center

Sunil Nagpal
Ph: 269-373-7458

Sunil Nagpal
Principal Investigator

Minnesota
Bemidji

Sanford Clinic North-Bemidgi

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Rochester

Mayo Clinic

Nadia Nicole Laack
Ph: 507-538-7623

Nadia Nicole Laack
Principal Investigator

Saint Cloud

Coborn Cancer Center at Saint Cloud Hospital

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

Donald James Jurgens
Principal Investigator

Saint Paul

Regions Hospital

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

Patrick James Flynn
Principal Investigator

United Hospital

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

Patrick James Flynn
Principal Investigator

Missouri
Kansas City

North Kansas City Hospital

Parvesh Kumar
Ph: 913-945-7552
Email: ctnursenav@kumc.edu

Parvesh Kumar
Principal Investigator

Montana
Billings

Billings Clinic Cancer Center

Benjamin T. Marchello
Ph: 800-648-6274

Benjamin T. Marchello
Principal Investigator

Montana Cancer Consortium CCOP

Paul D. Brown

Paul D. Brown
Principal Investigator

Nebraska
Omaha

University of Nebraska Medical Center

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

Andrew Owen Wahl
Principal Investigator

New Hampshire
Dover

Wentworth-Douglass Hospital

Arul Mahadevan
Ph: 603-740-2150

Arul Mahadevan
Principal Investigator

New Jersey
Somerville

Robert Wood Johnson University Hospital Somerset

Joel K. Braver
Ph: 908-685-2481

Joel K. Braver
Principal Investigator

New York
Syracuse

State University of New York Upstate Medical University

Seung Shin Hahn
Ph: 315-464-5476

Seung Shin Hahn
Principal Investigator

North Carolina
Chapel Hill

University of North Carolina at Chapel Hill

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

Timothy M. Zagar
Principal Investigator

Greenville

East Carolina University

Clinton H. Leinweber
Ph: 252-744-2391

Clinton H. Leinweber
Principal Investigator

North Dakota
Bismarck

Sanford Bismarck Medical Center

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Fargo

Roger Maris Cancer Center

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Sanford Clinic North-Fargo

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Ohio
Akron

Summa Akron City Hospital/Cooper Cancer Center

Charles Andrew Kunos
Ph: 330-375-6101

Charles Andrew Kunos
Principal Investigator

Cleveland

Case Western Reserve University

Min Yao
Ph: 800-641-2422

Min Yao
Principal Investigator

Cleveland Clinic Foundation

Samuel Tay Chao
Ph: 866-223-8100

Samuel Tay Chao
Principal Investigator

Westerville

Saint Ann's Hospital

John Philip Kuebler
Ph: 614-488-2745
Email: sheree@columbusccop.org

John Philip Kuebler
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

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

Terence S. Herman
Principal Investigator

Oregon
Portland

Legacy Good Samaritan Hospital and Medical Center

Andrew Y. Kee
Ph: 507-538-7623

Andrew Y. Kee
Principal Investigator

Pennsylvania
Abington

Abington Memorial Hospital

Wayne H. Pinover
Ph: 215-481-2402

Wayne H. Pinover
Principal Investigator

Danville

Geisinger Medical Center

Thomas James Gergel
Ph: 570-271-5251

Thomas James Gergel
Principal Investigator

Philadelphia

Aria Health-Torresdale Campus

Voichita Bar Ad
Ph: 215-955-6084

Voichita Bar Ad
Principal Investigator

South Dakota
Rapid City

Rapid City Regional Hospital

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

Joshua Cole Lukenbill
Principal Investigator

Sioux Falls

Sanford Cancer Center-Oncology Clinic

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Sanford USD Medical Center - Sioux Falls

Preston D. Steen
Ph: 701-234-6161

Preston D. Steen
Principal Investigator

Tennessee
Knoxville

Thompson Cancer Survival Center

Joseph Thurmond Meyer
Ph: 865-541-1812

Joseph Thurmond Meyer
Principal Investigator

Nashville

Vanderbilt University/Ingram Cancer Center

Albert Attia
Ph: 800-811-8480

Albert Attia
Principal Investigator

Texas
Galveston

University of Texas Medical Branch

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

Todd Allen Swanson
Principal Investigator

Utah
Murray

Intermountain Medical Center

R. Jeffrey Lee
Ph: 801-507-3950

R. Jeffrey Lee
Principal Investigator

Saint George

Dixie Medical Center Regional Cancer Center

R. Jeffrey Lee
Ph: 801-507-3950

R. Jeffrey Lee
Principal Investigator

Salt Lake City

Huntsman Cancer Institute/University of Utah

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

Dennis Charles Shrieve
Principal Investigator

Wisconsin
Green Bay

Saint Vincent Hospital

Anthony John Jaslowski
Ph: 800-432-6049

Anthony John Jaslowski
Principal Investigator

Milwaukee

Froedtert and the Medical College of Wisconsin

Joseph A. Bovi
Ph: 414-805-4380

Joseph A. Bovi
Principal Investigator

Waukesha

Waukesha Memorial Hospital

Timothy Robert Wassenaar
Ph: 262-928-7878

Timothy Robert Wassenaar
Principal Investigator

Canada

Nova Scotia
Halifax

QEII Health Sciences Centre/Capital District Health Authority

Liam Andrew Mulroy
Ph: 902-473-6000

Liam Andrew Mulroy
Principal Investigator

Ontario
Hamilton

Juravinski Cancer Centre at Hamilton Health Sciences

Anthony Charles Whitton
Ph: 905-387-9495

Anthony Charles Whitton
Principal Investigator

Toronto

University Health Network-Princess Margaret Hospital

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

Normand John Laperriere
Principal Investigator

Quebec
Montreal

CHUM - Hopital Notre-Dame

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

David Roberge
Principal Investigator

Sherbrooke

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

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

Laurence Masson-Cote
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01372774

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.