Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

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

Paul D. Brown

Principal Investigator

U.S.A.
Arizona
	Phoenix
	Arizona Oncology - Deer Valley Center
		David G. Brachman	Ph: 800-360-6371
California
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Eric L Chang	Ph: 323-865-0451
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Igor J Barani	Ph: 877-827-3222
Colorado
	Englewood
	Swedish Medical Center
		Eduardo R. Pajon	Ph: 888-785-6789
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo R. Pajon	Ph: 888-785-6789
Delaware
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Sunjay A Shah	Ph: 302-733-6227
Florida
	Miami Beach
	CCOP - Mount Sinai Medical Center
		Laurie E Blach	Ph: 305-674-2625
			Email: info@msccop.com
	Orlando
	M.D. Anderson Cancer Center at Orlando
		Naren R Ramakrishna	Ph: 321-841-7246
Illinois
	Oak Lawn
	Advocate Christ Medical Center
		Faisal S Vali	Ph: 800-323-8622
Indiana
	South Bend
	Memorial Hospital of South Bend
		Robin Zon	Ph: 574-234-5123
Iowa
	Cedar Rapids
	Mercy Regional Cancer Center at Mercy Medical Center
		Deborah W Wilbur	Ph: 319-363-2690
Kentucky
	Louisville
	Louisville Oncology at Norton Cancer Institute - Louisville
		Aaron C Spalding	Ph: 502-629-2500
Massachusetts
	Boston
	Tufts Medical Center Cancer Center
		Lynne P Taylor	Ph: 617-636-5000
			Email: ContactUsCancerCenter@TuftsMedicalCenter.org
	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
	Detroit
	Wayne State University
		Harold E. Kim	Ph: 313-576-9363
	Kalamazoo
	West Michigan Cancer Center
		Raymond Sterling Lord	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
	United Hospital
		Patrick J. Flynn	Ph: 952-993-1517
			Email: MMCCOP@parknicollet.com
Missouri
	Cape Girardeau
	Cape Radiation Oncology
		Tapan Roy	Ph: 866-334-2230
			Email: sfmc@sfmc.net
Montana
	Billings
	Billings Clinic Cancer Center - 801 N 29th Street
		Benjamin Thomas Marchello	Ph: 800-648-6274
New Hampshire
	Dover
	Seacoast Cancer Center at Wentworth - Douglass Hospital
		Arul Mahadevan	Ph: 603-740-2150
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
	Charlotte
	Presbyterian Cancer Center at Presbyterian Hospital
		Justin P Favaro	Ph: 704-384-5369
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		James J Urbanic	Ph: 336-713-6771
North Dakota
	Bismarck
	Bismarck Cancer Center
		John T Reynolds	Ph: 701-323-5760
			Email: tfischer@mohs.org
	Medcenter One Hospital Cancer Care Center
		John T Reynolds	Ph: 701-323-5760
			Email: tfischer@mohs.org
	Mid Dakota Clinic, PC
		Edward J. Wos	Ph: 701-323-5760
			Email: tfischer@mohs.org
	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: 800-641-2422
	Cleveland
	Case Comprehensive Cancer Center
		Simon Shek-Man Lo	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
	Tulsa
	Natalie Warren Bryant Cancer Center at St. Francis Hospital
		Charles E Stewart	Ph: 918-494-2200
Oregon
	Portland
	Legacy Good Samaritan Hospital & Comprehensive Cancer Center
		Andrew Y Kee	Ph: 507-538-7623
	Salem
	Salem Hospital Regional Cancer Care Services
		Edward Peter Orlowski	Ph: 503-561-2618
Pennsylvania
	Abington
	Rosenfeld Cancer Center at Abington Memorial Hospital
		Wayne H Pinover	Ph: 215-481-2402
	Allentown
	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
		Suresh G. Nair	Ph: 610-402-2273
	Danville
	Geisinger Cancer Institute at Geisinger Health
		Thomas J Gergel	Ph: 570-271-5251
	Philadelphia
	Frankford Hospital Cancer Center - Torresdale Campus
		Avnish Bhatia	Ph: 215-955-6084
South Dakota
	Rapid City
	Rapid City Regional Hospital
		Michael J Swartz	Ph: 605-716-3982
			Email: research@rcrh.org
Tennessee
	Knoxville
	Thompson Cancer Survival Center
		Joseph Thurmond Meyer	Ph: 865-541-1812
Texas
	Galveston
	University of Texas Medical Branch
		Todd A Swanson	Ph: 409-772-1950
			Email: clinical.research@utmb.edu
Utah
	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
	Marshfield
	Marshfield Clinic - Marshfield Center
		Benjamin E. Lawler	Ph: 715-389-4457
	Saint Joseph's Hospital
		Benjamin E. Lawler	Ph: 715-389-4457
	Milwaukee
	Vince Lombardi Cancer Clinic at Aurora St. Luke's Medical Center
		Mitchell H. Pincus	Ph: 800-252-2990
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 Identifer NCT01372774
Information obtained from ClinicalTrials.gov on February 27, 2013

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