Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Zoledronate in Preventing Skeletal (Bone)-Related Events in Patients Who Are Receiving Androgen Deprivation Therapy For Prostate Cancer and Bone Metastases

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI CALGB-90202 CALGB-90202, ECOG-CALGB-90202, NCT00079001, SWOG-CALGB-90202, CAN-NCIC-PRC2

Special Category: CTSU trial, NCI Web site featured trial

Objectives

Primary

1. Compare the time to first skeletal-related events in patients with prostate cancer and bone metastases undergoing androgen deprivation therapy when treated with zoledronate vs placebo.

Secondary

1. Compare the overall and progression-free survival of patients treated with these regimens.
2. Compare the toxic effects in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate



• No small cell, neuroendocrine, or transitional cell carcinomas



• At least 1 bone metastasis by bone scan, MRI, CT scan, or plain radiographs
  • Indeterminate lesions should be confirmed by a second imaging method
  • At least 1 bone metastasis with no prior irradiation



• Concurrent androgen deprivation therapy required, defined as any of the following:
  • Bilateral orchiectomy
  • Gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen

Prior/Concurrent Therapy:

Biologic therapy

• Concurrent standard biologic response modifiers allowed during open-label therapy only

Chemotherapy

• Concurrent standard cytotoxic chemotherapy allowed during open-label therapy only

Endocrine therapy

• See Disease Characteristics
• Prior neoadjuvant and/or adjuvant hormonal therapy allowed provided duration of therapy was no more than 6 months AND therapy was discontinued more than 6 months before study entry
• No more than 6 months since initiation of any of the following hormonal therapies:
  • Orchiectomy
  • GnRH agonist (e.g., leuprolide, goserelin, or triptorelin)
  • Estrogen therapy
  • Antiandrogens (e.g., bicalutamide, flutamide, or nilutamide)
  • Any other therapy known to lower testosterone levels or inhibit testosterone effect
• No intermittent androgen deprivation therapy except for patients concurrently enrolled on SWOG-9346
• Concurrent palliative corticosteroids allowed during open-label therapy only
• Concurrent standard hormonal agents allowed during open-label therapy only

Radiotherapy

• See Disease Characteristics
• No prior radiopharmaceuticals
• At least 4 weeks since prior radiotherapy
• Concurrent standard radiotherapy to extraskeletal and/or skeletal tumor sites allowed during open-label therapy only

Surgery

• See Disease Characteristics

Other

• No prior bisphosphonates
• No other concurrent agents expected to alter osteoclast activity (e.g., calcitonin, mithramycin, gallium nitrate, or any other bisphosphonate)
• Concurrent daily supplemental elemental calcium (500 mg) and a multivitamin containing cholecalciferol (Vitamin D) (400 IU) OR a combination tablet containing both recommended
• Concurrent standard marketed antineoplastic therapies allowed during open-label therapy only

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine clearance ≥ 30 mL/min
• Corrected calcium ≥ 8.0 mg/dL and < 11.6 mg/dL

Other

• Fertile patients must use effective contraception

Expected Enrollment

A total of 680 patients (340 per treatment arm) will be accrued for this study within 4 years.

Outcomes

Time to first skeletal related event

Overall survival
Progression-free survival
Toxicity

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study followed by an open-label study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior skeletal-related event (no vs yes), and serum alkaline phosphatase (< upper limit of normal [ULN] vs ≥ ULN). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes on day 1.



• Arm II: Patients receive placebo IV over 15 minutes on day 1.

In both arms, courses repeat every 4 weeks in the absence of disease progression or a skeletal-related event. All patients receive concurrent androgen deprivation therapy. Patients also receive oral calcium and cholecalciferol (vitamin D) supplements daily.

Patients progressing to androgen-independent prostate cancer proceed to open-label therapy comprising zoledronate IV over 15 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or a skeletal-related event.

Patients are followed periodically for approximately 10 years after randomization.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Matthew Smith, MD, Protocol chair		Ph: 617-724-5257; 877-726-5130

Southwest Oncology Group

Nirmala Bhoopalam, MD, Protocol chair		Ph: 708-202-2782 Email: nirmala.bhoopalam@med.va.gov

Eastern Cooperative Oncology Group

Christopher Sweeney, MBBS, Protocol chair		Ph: 317-274-3515; 888-600-4822 Email: chsweene@iupui.edu

NCIC-Clinical Trials Group

Fred Saad, MD, FRCS, Protocol chair		Ph: 514-890-8000 ext 27466 Email: fred.saad.chum@ssss.gouv.qc.ca

U.S.A.
Arkansas
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Loma Linda
	Veterans Affairs Medical Center - Loma Linda (Pettis)
		Mark Reeves, MD, PhD	Ph:  909-825-7084ext.6064
	Pomona
	Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
		Clinical Trials Office - Robert and Beverly Lewis Family Cancer Care Center	Ph:  909-865-9555
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Montrose
	Montrose Memorial Hospital Cancer Center
		Clinical Trials Office - Montrose Memorial Hospital Cancer Center	Ph:  670-240-7267
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
District of Columbia
	Washington
	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
		Clinical Trials Office - Lombardi Comprehensive Cancer Center	Ph:  202-444-0381
Florida
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Leesburg
	Cancer Centers of Central Florida, PA
		Donald Elmajian, MD	Ph:  318-813-1200
Georgia
	Augusta
	MBCCOP - Medical College of Georgia Cancer Center
		Anand Jillella, MD	Ph:  706-721-2505
	Savannah
	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
		Mark Taylor, MD	Ph:  912-354-6187
Idaho
	Idaho Falls
	Snake River Oncology of Eastern Idaho PLLC
		Christian Shull	Ph:  208-523-1100
Illinois
	Alton
	Saint Anthony's Hospital at Saint Anthony's Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3019
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Elmhurst
	Elmhurst Memorial Hospital
		Gerald Kozuh, MD	Ph:  630-614-4060
	Hines
	Veterans Affairs Medical Center - Hines
		Nirmala Bhoopalam, MD	Ph:  708-202-2782
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3019
	Kankakee
	Provena St. Mary's Regional Cancer Center - Kankakee
		Riaz Elahi, MD	Ph:  708-873-4500
	La Grange
	La Grange Memorial Hospital
		Clinical Trials Office - La Grange Memorial Hospital	Ph:  630-856-7526
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Olympia Fields
	Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields
		Clinical Trials Office - Saint James Hospital and Health Centers Comprehensive Cancer Institute - Olympia Fields	Ph:  708-679-2217
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Indianapolis
	Indiana University Melvin and Bren Simon Cancer Center
		Clinical Trials Office - Indiana University Cancer Center	Ph:  317-274-2552
	William N. Wishard Memorial Hospital
		Noah Hahn	Ph:  317-639-6671
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3019
Iowa
	Council Bluffs
	Alegent Health Mercy Hospital
		Gamini Soori, MD, FACP, FRCP, MBA	Ph:  402-393-3110
	Heartland Oncology and Hematology
		John Okerbloom, MD	Ph:  712-322-4136
	Waterloo
	Cedar Valley Medical Specialists, PC - West Ridgeway Avenue
		Boriana Kamenova	Ph:  319-833-5907
	Covenant Cancer Treatment Center
		Clinical Trials Office - Covenant Cancer Treatment Center	Ph:  319-272-2070
Kansas
	Kansas City
	Providence Medical Center
		Rakesh Gaur, MD	Ph:  816-823-0555
	Lawrence
	Lawrence Memorial Hospital
		Rakesh Gaur, MD	Ph:  816-823-0555
	Overland Park
	Johnson County Radiation Therapy
		Rakesh Gaur, MD	Ph:  816-823-0555
	Menorah Medical Center
		Rakesh Gaur, MD	Ph:  816-823-0555
	Shawnee Mission
	Shawnee Mission Medical Center
		Rakesh Gaur, MD	Ph:  816-823-0555
	Topeka
	Cotton-O'Neil Cancer Center
		Clinical Trials Office - Cotton-O'Neil Cancer Center	Ph:  785-270-4963
	St. Francis Comprehensive Cancer Center
		Michael Hurwitz, MD	Ph:  785-295-7800
Louisiana
	Monroe
	Louisiana State University Health Sciences Center - Monroe
		Donald Elmajian, MD	Ph:  318-813-1200
	Shreveport
	Feist-Weiller Cancer Center at Louisiana State University Health Sciences
		Clinical Trials Office - Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Ph:  318-813-1412
	Highland Clinic
		Donald Elmajian, MD	Ph:  318-813-1200
	Veterans Affairs Medical Center - Shreveport
		Donald Elmajian, MD	Ph:  318-813-1200
Maine
	Lewiston
	Central Maine Comprehensive Cancer Center at Central Maine Medical Center
		Nicholette Erickson, MD	Ph:  207-795-2935
	Waterville
	MaineGeneral Medical Center - Waterville
		Clinical Trials Office - MaineGeneral Medical Center - Waterville	Ph:  207-872-1792
Maryland
	Baltimore
	Greenebaum Cancer Center at University of Maryland Medical Center
		Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center	Ph:  800-888-8823
	Veterans Affairs Medical Center - Baltimore
		Arif Hussain, MD	Ph:  410-328-7225
	Easton
	Shore Regional Cancer Center at Memorial Hospital - Easton
		John P. Foley, MD	Ph:  210-916-0716
	Elkton MD
	Union Hospital Cancer Program at Union Hospital
		Stephen Grubbs, MD	Ph:  302-366-1200
	Largo
	Kaiser Permanente Mid-Atlantic Medical Group-Largo Medical Facility
		Leon Hwang, MD	Ph:  301-548-5768
	Lutherville
	Kaiser Permanente - Towson
		Leon Hwang, MD	Ph:  301-548-5768
	Rockville
	Kaiser Permanente Capital Area Medical Group - Shady Grove Facility
		Leon Hwang, MD	Ph:  301-548-5768
Massachusetts
	Boston
	Boston University Cancer Research Center
		Clinical Trials Office - Boston University Cancer Research Center	Ph:  617-353-7571
	Dana-Farber/Brigham and Women's Cancer Center
		Clinical Trials Office	Ph:  617-724-5200
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Matthew Smith, MD	Ph:  617-724-5257
	Massachusetts General Hospital
		Clinical Trials Office - Massachusetts General Hospital	Ph:  877-726-5130
Michigan
	Adrian
	Hickman Cancer Center at Bixby Medical Center
		Clinical Trials Office - Hickman Cancer Center at Bixby Medical Center	Ph:  517-265-0116
	Detroit
	Josephine Ford Cancer Center at Henry Ford Hospital
		Robert Chapman, MD	Ph:  313-916-1332
	Escanaba
	Green Bay Oncology, Limited - Escanaba
		Thomas Saphner, MD, FACP	Ph:  920-884-3135
	Iron Mountain
	Dickinson County Healthcare System
		Thomas Saphner, MD, FACP	Ph:  920-884-3135
	Kalamazoo
	Borgess Medical Center
		Raymond Lord, MD	Ph:  269-373-7458
	Bronson Methodist Hospital
		Raymond Lord, MD	Ph:  269-373-7458
	West Michigan Cancer Center
		Clinical Trials Office - West Michigan Cancer Center	Ph:  269-373-7458
	Lambertville
	Haematology-Oncology Associates of Ohio and Michigan, PC
		Paul Schaefer, MD	Ph:  419-479-5605
	Monroe
	Community Cancer Center of Monroe
		Paul Schaefer, MD	Ph:  419-479-5605
	Mercy Memorial Hospital - Monroe
		Paul Schaefer, MD	Ph:  419-479-5605
Minnesota
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Duluth
	CCOP - Duluth
		Daniel Nikcevich, MD, PhD	Ph:  218-786-3625
	Duluth Clinic Cancer Center - Duluth
		Clinical Trials Office - Duluth Clinic Cancer Center - Duluth	Ph:  218-786-3308
	Miller - Dwan Medical Center
		Daniel Nikcevich, MD, PhD	Ph:  218-786-3625
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Mankato
	Immanuel St. Joseph's
		Glenn Harman, MD	Ph:  815-777-1536
	Maplewood
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center