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

Alternate Title

Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over NCI SWOG-S0221 S0221, NCT00070564

Special Category: CTSU trial, NCI Web site featured trial

Objectives

1. Compare the disease-free survival of patients with node-positive or high-risk node-negative breast cancer treated with 4 different schedules of adjuvant doxorubicin, cyclophosphamide, and paclitaxel.
2. Compare the overall survival of patients treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Correlate outcome with putative prognostic markers in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage I-III invasive breast cancer
  • Operable disease
  • Stage I, II, IIIA, and IIIC (T1-3, N3a only)
  • No T4 tumors



• High-risk disease, defined by 1 of the following:
  • Tumor ≥ 2 cm in greatest diameter (includes both invasive and intraductal component)
    • Patients with nodal status of N0+ (i.e., no cluster of tumor cells in any node greater than 0.2 mm) are considered to be node negative and must have a primary tumor ≥ 2 cm in size or have a tumor ≥ 1 cm with high risk features
    • Patients who are node negative on the basis of a sentinel node procedure and fewer than 6 axillary nodes are removed are eligible OR at least 6 axillary or intramammary nodes must be negative
  • Tumor ≥ 1 cm in diameter and meeting 1 of the following criteria:
    • ER-negative and PgR-negative
    • ER-positive or PgR-positive with a Genomic Health Recurrence Score of ≥ 26
  • One or more axillary or intramammary nodes are involved by metastatic breast cancer
    • If one or more nodes is involved, a minimum of 6 axillary or intramammary nodes must have been examined histologically
    • Patients with N0(I+) disease will be considered node negative



• HER2/neu-positive tumors (3+ by immunohistochemical staining or amplified by fluorescence in-situ hybridization) allowed



• Bilateral synchronous breast cancer diagnosed within 1 month of each other allowed provided the higher TNM stage primary tumor meets the eligibility criteria



• Prior modified radical mastectomy OR local excision of all tumors with axillary lymph node dissection or sentinel node resection required
  • No more than 84 days since prior surgery for the primary tumor and/or axilla
  • Final resection margins for the primary tumor must be histologically negative for invasive cancer and ductal carcinoma in situ
  • Resection margins positive for lobular carcinoma in situ are allowed



• Hormone receptor status:
  • Estrogen receptor status known
  • Progesterone receptor status known

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior cytotoxic chemotherapy for this breast cancer
• No prior chemotherapy with an anthracycline, anthracenedione, or taxane

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this malignancy
• At least 2 weeks since prior radiotherapy for ductal carcinoma in situ

Surgery

• See Disease Characteristics

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,200/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2 times ULN
• SGOT or SGPT no greater than 2 times ULN

Renal

• Creatinine no greater than ULN

Cardiovascular

• No congestive heart failure
• No active angina pectoris
• LVEF greater than or equal to the lower limit of normal* by MUGA or echocardiogram

 [Note: Patients age 60 and over OR with a history of hypertension]

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical carcinoma, or lobular carcinoma in situ of the breast
  • Prior invasive breast cancer or ductal carcinoma in situ allowed if disease-free for 5 years
• HIV negative

Expected Enrollment

A total of 4,500 patients (1,125 per treatment arm) will be accrued for this study within 2.25 years.

Outcomes

Disease-free survival by medical history, physical exam, and mammograms every 6 months (annually for mammograms) for 5 years and then annually for 15 years or until death
Compare overall survival of patients among the 4 treatment arms by medical history and physical exam every 6 months for 5 years and then annually
Compare toxicity among the 4 treatment arms by medical history and physical exam every 6 months for 5 years and then annually

Compare disease-free survival of patients among the 4 treatment arms by assessment of medical history, physical exam, and mammograms every 6 months (annually for mammograms) for 5 years and then annually for 15 years or until death
Compare prognostic biomarkers with outcome and the interaction of these markers with treatment as measured by gene expression analysis before study entry

Outline

This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 2 or filgrastim (G-CSF) SC on days 3-10. Treatment repeats every 14 days for 6 courses.

  Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.




• Arm II: Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and G-CSF SC on days 2-7. Treatment repeats every 7 days for 15 courses.

  Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel and pegfilgrastim as in arm I.




• Arm III: Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I.

  Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.




• Arm IV: Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II.

  Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

In all arms patients with HER2/neu-positive tumors also receive trastuzumab (Herceptin®) weekly or every 3 weeks beginning concurrently with paclitaxel OR 3 months after the last dose of paclitaxel and continuing for up to 52 weeks.

In all arms, patients with estrogen-receptor or progesterone-receptor positive tumors receive hormonal therapy beginning within 28 days of the completion of adjuvant chemotherapy or radiotherapy (if given).

After finishing study treatment patients are followed once a year for up to 15 years.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

George Budd, MD, Study coordinator		Ph: 216-444-6480; 800-862-7798 Email: S0221@cc.ccf.org
Halle Moore, MD, Study coordinator		Ph: 216-445-4624; 800-862-7798

U.S.A.
Alabama
	Anniston
	Regional Medical Center
		Stephanie Fussell	Ph:  256-235-5877
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	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
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	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
	Ft. Smith
	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
		John Wells, MD	Ph:  479-484-4700
	Jonesboro
	Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center
		Clinical Trials Office - Ben E. Owens Cancer Treatment Center at St. Bernard's Medical Center	Ph:  870-972-4100
	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
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Fresno
	California Cancer Center - Woodward Park Office
		Dina Ibrahim	Ph:  559-451-3647
	Greenbrae
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-1591
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-1591
	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
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Palm Springs
	Desert Regional Medical Center Comprehensive Cancer Center
		Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center	Ph:  760-416-4730
	Roseville
	Sutter Cancer Center at Roseville Medical Center
		Clinical Trials Office - Sutter Cancer Center	Ph:  916-454-6595
	Sacramento
	Mercy General Hospital
		Colin Spears, MD	Ph:  916-736-1536
	Sutter Cancer Center
		Clinical Trial Office - Sutter Cancer Center	Ph:  916-454-6595
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-1591
	San Francisco General Hospital Medical Center
		Hope Rugo, MD	Ph:  415-353-7428
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	Stockton
	St. Joseph's Regional Cancer Center
		Aminder Mehdi, MD	Ph:  209-466-2626
	Vallejo
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-1591
Colorado
	Aurora
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Denver
	Denver Health Medical Center
		Anthony Elias, MD	Ph:  720-848-1622
	Veterans Affairs Medical Center - Denver
		Anthony Elias, MD	Ph:  720-848-1622
	Edwards
	Shaw Regional Cancer Center
		Anthony Elias, MD	Ph:  720-848-1622
	Montrose
	Montrose Memorial Hospital Cancer Center
		Clinical Trials Office - Montrose Memorial Hospital Cancer Center	Ph:  670-240-7267
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
	Fort Lauderdale
	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
		Clinical Trials Office - Michael and Dianne Bienes Comprehensive Cancer Center	Ph:  954-776-3239
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Jupiter
	Ella Milbank Foshay Cancer Center at Jupiter Medical Center
		Clinical Trials Office - Ella Milbank Foshay Cancer Center	Ph:  561-745-5768
	Leesburg
	Cancer Centers of Central Florida, PA
		Glenn Mills, MD	Ph:  318-813-1440
	Miami Beach
	CCOP - Mount Sinai Medical Center
		Michael Schwartz, MD	Ph:  305-535-3310
Georgia
	Columbus
	John B. Amos Cancer Center
		Clinical Trials Office - John B. Amos Cancer Center	Ph:  706-660-6404
	Fort Gordon
	Dwight David Eisenhower Army Medical Center
		Mary Edgecomb, DO	Ph:  706-787-2100
	Valdosta
	Pearlman Comprehensive Cancer Center at South Georgia Medical Center
		Contact Person	Ph:  229-259-4600
Hawaii
	Aiea
	Kapiolani Medical Center at Pali Momi
		Jonathan Cho	Ph:  808-486-6000
	Honolulu
	Cancer Research Center of Hawaii
		Clinical Trials Office - Cancer Research Center of Hawaii	Ph:  808-586-2979
	Hawaii Medical Center - East
		Jonathan Cho	Ph:  808-547-6011
	Kapiolani Medical Center for Women and Children
		Jonathan Cho	Ph:  808-973-8511
	OnCare Hawaii, Incorporated - Kuakini
		Jonathan Cho	Ph:  808-531-8521
	OnCare Hawaii, Incorporated - Lusitana
		Jonathan Cho	Ph:  808-524-6115
	Queen's Cancer Institute at Queen's Medical Center
		Jonathan Cho	Ph:  808-545-8778 800-547-4742
	Straub Clinic and Hospital, Incorporated
		Jonathan Cho	Ph:  808-522-4000 800-232-9491
	Tripler Army Medical Center
		Jeffrey Berenberg, MD	Ph:  808-433-4089
	Wailuku
	Maui Memorial Medical Center
		Jonathan Cho	Ph:  808-244-9056
	Pacific Cancer Institute - Maui
		Jonathan Cho	Ph:  808-242-2600
Idaho
	Boise
	Mountain States Tumor Institute at St. Luke's Regional Medical Center
		Theodore Walters, MD	Ph:  208-381-2711
	Coeur d'Alene
	Kootenai Cancer Center - Coeur d'Alene
		Clinical Trials Office - North Idaho Cancer Center	Ph:  208-666-3764
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
	Bloomington
	St. Joseph Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3605
	Carthage
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3605
	Chicago
	Resurrection Medical Center
		Christopher Rose, MD	Ph:  847-965-3200
	Robert H. Lurie Comprehensive Cancer Center at Northwestern University
		Clinical Trials Office - Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Ph:  312-695-1301
			Email: cancer@northwestern.edu
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-6601
	Elk Grove Village
	Alexian Brothers Radiation Oncology
		Bruce Bank, MD	Ph:  847-437-3312
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3605
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3605
	Galesburg Cottage Hospital
		John Kugler, MD	Ph:  309-243-3605
	Harvey
	Ingalls Cancer Care Center at Ingalls Memorial Hospital
		Clinical Trials Office - Ingalls Cancer Care Center at Ingalls Memorial Hospital	Ph:  708-915-6747
	Havana
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Hopedale
	Hopedale Medical Complex
		John Kugler, MD	Ph:  309-243-3605
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Sanjiv Modi	Ph:  815-730-3098
	Macomb
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3605
	Maywood
	Cardinal Bernardin Cancer Center at Loyola University Medical Center
		Clinical Trials Office - Cardinal Bernardin Cancer Center	Ph:  708-226-4357
	Mt. Vernon
	Good Samaritan Regional Health Center
		Bethany Sleckman, MD	Ph:  314-251-7057
	Naperville
	Edward Hospital Cancer Center
		Clinical Trials Office - Edward Hospital Cancer Center	Ph:  630-646-6075
	Hematology Oncology Consultants - Naperville
		Fariborze Barhamand, MD	Ph:  630-369-1501
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3605
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3605
	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
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3605
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3605