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

Alternate Title

Zoledronate, Clodronate, or Ibandronate in Treating Women Who Have Undergone Surgery for Stage I, Stage II, or Stage III Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI SWOG-S0307 NCCTG-SWOG-S0307, ECOG-SWOG-S0307, NSABP-SWOG-S0307, CALGB-SWOG-S0307, CAN-NCIC-SWOG-S0307, S0307, NCT00127205

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Compare disease-free survival and overall survival of women with resected primary stage I-III adenocarcinoma of the breast treated with adjuvant zoledronate vs clodronate vs ibandronate.
2. Compare the distributions of sites of first disease recurrence in patients treated with these drugs.
3. Compare adverse events in patients treated with these drugs.
4. Correlate parathyroid hormone related protein status and N-telopeptide levels at baseline with disease-free survival and sites of first recurrence in patients treated with these drugs.

Entry Criteria

Disease Characteristics:

• Histologically confirmed primary adenocarcinoma of the breast
  • Stage I-III disease
  • No evidence of metastatic disease



• Must have undergone lumpectomy or total mastectomy for primary disease within the past 12 weeks, or have completed chemotherapy within the past 8 weeks
  • Axillary evaluation per institutional standards



• Currently receiving or planning to receive standard adjuvant systemic therapy comprising chemotherapy, hormonal therapy, or combined chemotherapy/hormonal therapy for breast cancer
  • Patients who are at low risk for disease recurrence and for whom adjuvant systemic therapy will not be prescribed are not eligible
  • Patients who receive biologic agents only or local radiotherapy only (without chemotherapy and/or hormone therapy) are not eligible
  • Additional therapies are allowed including radiotherapy and biologic agents (e.g., trastuzumab [Herceptin^®], bevacizumab, or hematopoietic growth factors)
  • Neoadjuvant therapy is allowed provided study entry occurs after completion of surgery



• Patients with skeletal pain are eligible provided bone scan and/or roentgenological exam are negative for metastatic disease
  • Suspicious findings must be confirmed as benign by x-ray, MRI, or biopsy



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• Prior or concurrent hematopoietic growth factors allowed
• HER-2-targeted therapies allowed
• Antiangiogenics allowed

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Concurrent radiotherapy to the breast, chest wall, or lymph node group allowed at the discretion of the treating physician

Surgery

• See Disease Characteristics

Other

• Prior neoadjuvant therapy allowed
• Prior bisphosphonates for bone density allowed
• No other concurrent bisphosphonates as adjuvant therapy or for treatment of osteoporosis
• No concurrent enrollment in clinical trials with bone density as an endpoint
  • Concurrent enrollment on any other locoregional or systemic therapy breast cancer study (including cooperative group studies) allowed

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine ≤ 2 times upper limit of normal
• Creatinine clearance ≥ 30 mL/min
• No renal failure

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of esophageal stricture or motility disorders
  • Gastroesophageal reflux disorder allowed
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

Expected Enrollment

A total of 4,500 will be accrued for this study.

Outcomes

Histologic confirmation of disease recurrence
Sites of first disease recurrence
Disease-free survival
Overall survival
Zubrod performance status

Outline

This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive zoledronate IV over 15 minutes once a month for 6 months and then once every 3 months for 2.5 years.



• Arm II: Patients receive oral clodronate once daily for 3 years.



• Arm III: Patients receive oral ibandronate once daily for 3 years.

Treatment in all arms continues in the absence of disease recurrence or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months until disease recurrence and then annually for up to 10 years.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Julie Gralow, MD, Study coordinator		Ph: 206-288-7722 Email: pink@u.washington.edu
Robert Livingston, MD, Study coordinator		Ph: 206-288-1085

North Central Cancer Treatment Group

James Ingle, MD, Study coordinator		Ph: 507-284-2511 Email: ingle.james@mayo.edu

Eastern Cooperative Oncology Group

Carla Falkson, MD, Study coordinator		Ph: 205-975-2691 Email: cfalkson@uab.edu

National Surgical Adjuvant Breast and Bowel Project

Alexander Paterson, MD, FRCP, FACP, MBChB, Study coordinator		Ph: 403-521-3688 Email: alexpate@cancerboard.ab.ca

Cancer and Leukemia Group B

Elizabeth Dees, MD, Study coordinator		Ph: 919-843-7714

NCIC-Clinical Trials Group

Mark Clemons, MD, Study coordinator		Ph: 416-480-5847 Email: mark.clemons@sw.ca

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U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Stephanie Fussell	Ph:  256-235-5877
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-544-1013
Alaska
	Anchorage
	Alaska Regional Hospital Cancer Center
		Saul Rivkin, MD	Ph:  206-386-2441
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
	Fairbanks
	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
		Jacqueline Vuky	Ph:  907-458-5380 800-678-5458
Arizona
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008
Arkansas
	Bentonville
	Highlands Oncology Group - Springdale
		Joseph Beck, MD, FACP	Ph:  479-587-1700
	Hot Springs
	St. Joseph's Mercy Cancer Center
		Prabhakara Reddy	Ph:  501-623-2731
	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
	Arroyo Grande
	Arroyo Grande Community Hospital
		David Palchak, MD	Ph:  805-773-7127
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Castro Valley
	East Bay Radiation Oncology Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Washington Township Hospital
		Byron Wilson, MD	Ph:  510-888-0657
	Glendale
	Glendale Memorial Hospital Comprehensive Cancer Center
		Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center	Ph:  818-409-7653
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Long Beach
	Breastlink Medical Group, Incorporated at Long Beach Memorial Medical Center
		Clinical Trials Office - Breastlink Medical Group, Incorporated	Ph:  562-981-6101
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Martinez
	Contra Costa Regional Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Marysville
	Tibotec Therapeutics - Division of Ortho Biotech Products, LP
		Helen Chew, MD	Ph:  916-734-3771
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Palm Springs
	Desert Regional Medical Center Comprehensive Cancer Center
		Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center	Ph:  760-416-4730
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	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
	Redding
	Mercy Regional Cancer Center at Mercy Medical Center
		Clinical Trials Office - Mercy Regional Cancer Center	Ph:  530-225-7471
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	San Francisco
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Francisco General Hospital Medical Center
		Judith Luce, MD	Ph:  415-476-4082ext.414
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Truckee
	Tahoe Forest Cancer Center
		Helen Chew, MD	Ph:  916-734-3771
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Walnut Creek
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Boulder
	Boulder Community Hospital
		Clinical Trials Office - Boulder Community Hospital	Ph:  303-938-5253
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Denver Health Medical Center
		Anthony Elias, MD	Ph:  720-848-1622
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Veterans Affairs Medical Center - Denver
		Anthony Elias, MD	Ph:  720-848-1622
	Edwards
	Shaw Regional Cancer Center
		Anthony Elias, MD	Ph:  720-848-1622
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Glenwood Springs
	Valley View Hospital Cancer Center
		Anthony Elias, MD	Ph:  720-848-1622
	Grand Junction
	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Greeley
	North Colorado Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Lone Tree
	Sky Ridge Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Longmont
	Hope Cancer Care Center at Longmont United Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Loveland
	McKee Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Montrose
	Montrose Memorial Hospital Cancer Center
		Clinical Trials Office - Montrose Memorial Hospital Cancer Center	Ph:  670-240-7267
	Pueblo
	St. Mary - Corwin Regional Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Thornton
	North Suburban Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Wheat Ridge
	Exempla Lutheran Medical Center
		Clinical Trials Office - Exempla Lutheran Medical Center	Ph:  303-403-3605
Connecticut
	Greenwich
	Bendheim Cancer Center at Greenwich Hospital