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.
Michigan
	Lambertville
	Haematology-Oncology Associates of Ohio and Michigan, PC
		Paul Schaefer, MD	Ph:  419-479-5605
Ohio
	Bowling Green
	Wood County Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Maumee
	Northwest Ohio Oncology Center
		Paul Schaefer, MD	Ph:  419-479-5605
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Luke's Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Oregon
	St. Charles Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic - Oregon
		Paul Schaefer, MD	Ph:  419-479-5605
	Sylvania
	Flower Hospital Cancer Center
		Clinical Trials Office - Flower Hospital Cancer Center	Ph:  419-824-1842
	Toledo
	CCOP - Toledo Community Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	Medical University of Ohio Cancer Center
		Clinical Trials Office - Medical University of Ohio Cancer Center	Ph:  419-383-6583
	St. Anne Mercy Hospital
		Paul Schaefer, MD	Ph:  419-479-5605
	St. Vincent Mercy Medical Center
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Clinic, Incorporated - Main Clinic
		Paul Schaefer, MD	Ph:  419-479-5605
	Toledo Hospital
		Clinical Trials Office - Toledo Hospital	Ph:  419-824-1842

See All Trial Sites

Related Information

Featured trial article

Registry Information
Official Title		Phase III Trial of Continuous Schedule AC + G vs. Q 2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer
Trial Start Date		2003-11-01
Trial Completion Date		2012-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00070564
Date Submitted to PDQ		2003-09-08
Information Last Verified		2010-02-07
NCI Grant/Contract Number		CA32102

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